umu.sePublications
Change search
Refine search result
123 51 - 100 of 112
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Jagarlamudi, Krishna
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Liu, Lian
    Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, China.
    Adhikari, Deepak
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Reddy, Pradeep
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Liu, Kui
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Oocyte-specific deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation2009In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 7, p. e6186-Article in journal (Refereed)
    Abstract [en]

    Immature ovarian primordial follicles are essential for maintenance of the reproductive lifespan of female mammals. Recently, it was found that overactivation of the phosphatidylinositol 3-kinase (PI3K) signaling in oocytes of primordial follicles by an oocyte-specific deletion of Pten (phosphatase and tensin homolog deleted on chromosome ten), the gene encoding PI3K negative regulator PTEN, results in premature activation of the entire pool of primordial follicles, indicating that activation of the PI3K pathway in oocytes is important for control of follicular activation. To investigate whether PI3K signaling in oocytes of primary and further developed follicles also plays a role at later stages in follicular development and ovulation, we conditionally deleted the Pten gene from oocytes of primary and further developed follicles by using transgenic mice expressing zona pellucida 3 (Zp3) promoter-mediated Cre recombinase. Our results show that Pten was efficiently deleted from oocytes of primary and further developed follicles, as indicated by the elevated phosphorylation of the major PI3K downstream component Akt. However, follicular development was not altered and oocyte maturation was also normal, which led to normal fertility with unaltered litter size in the mutant mice. Our data indicate that properly controlled PTEN/PI3K-Akt signaling in oocytes is essential for control of the development of primordial follicles whereas overactivation of PI3K signaling in oocytes does not appear to affect the development of growing follicles. This suggests that there is a stage-specific function of PTEN/PI3K signaling in mouse oocytes that controls follicular activation.

  • 52.
    Jonsson, Sarah
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Oda, Husam
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Chlamydia trachomatis, Chlamydial Heat Shock Protein 60 and Anti-Chlamydial Antibodies in Women with Epithelial Ovarian Tumors2018In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 11, no 2, p. 546-551Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Chlamydia trachomatis (C. trachomatis) infection has been suggested to promote epithelial ovarian cancer (EOC) development. This study sought to explore the presence of C. trachomatis DNA and chlamydial heat shock protein 60 (chsp60) in ovarian tissue, as well as anti-chlamydial IgG antibodies in plasma, in relation to subtypes of EOC. METHODS: This cross-sectional cohort consisted of 69 women who underwent surgery due to suspected ovarian pathology. Ovarian tissue and corresponding blood samples were collected at the time of diagnosis. In ovarian tumor tissue, p53, p16, Ki67 and chsp60 were analyzed immunohistochemically, and PCR was used to detect C. trachomatis DNA. Plasma C. trachomatis IgG and cHSP60 IgG were analyzed with a commercial MIF-test and ELISA, respectively. RESULTS: Eight out of 69 women had C. trachomatis DNA in their ovarian tissue, all were invasive ovarian cancer cases (16.7% of invasive EOC). The prevalence of the chsp60 protein, C. trachomatis IgG and cHSP60 IgG in HGSC, compared to other ovarian tumors, was 56.0% vs. 37.2% P = .13, 15.4% vs. 9.3% P = .46 and 63.6% vs. 45.5% P = .33 respectively. None of the markers of C. trachomatis infection were associated with p53, p16 or Ki67. CONCLUSIONS: C. trachomatis was detected in invasive ovarian cancer, supporting a possible role in carcinogenesis of EOC. However, there were no statistically significant associations of chsp60 in ovarian tissue, or plasma anti-chlamydial IgG antibodies, with any of the subtypes of ovarian tumors.

  • 53. Jung, Seungyoun
    et al.
    Allen, Naomi
    Arslan, Alan A.
    Baglietto, Laura
    Barricarte, Aurelio
    Brinton, Louise A.
    Egleston, Brian L.
    Falk, Roni T.
    Fortner, Renée T.
    Helzlsouer, Kathy J.
    Gao, Yutang
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Kaaks, Rudolph
    Krogh, Vittorio
    Merritt, Melissa A.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Onland-Moret, N. Charlotte
    Rinaldi, Sabina
    Schock, Helena
    Shu, Xiao-Ou
    Sluss, Patrick M.
    Staats, Paul N.
    Sacerdote, Carlotta
    Travis, Ruth C.
    Tjønneland, Anne
    Trichopoulou, Antonia
    Tworoger, Shelley S.
    Visvanathan, Kala
    Weiderpass, Elisabete
    Zeleniuch-Jacquotte, Anne
    Dorgan, Joanne F.
    Anti‐Müllerian hormone and risk of ovarian cancer in nine cohorts2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 2, p. 262-270Article in journal (Refereed)
    Abstract [en]

    Animal and experimental data suggest that anti‐Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case‐control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme‐linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable‐adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable‐adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59–1.67) (Ptrend: 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity: ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity: ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.

  • 54. Jung, Seungyoun
    et al.
    Allen, Naomi
    Arslan, Alan A.
    Baglietto, Laura
    Brinton, Louise A.
    Egleston, Brian L.
    Falk, Roni
    Fortner, Renee T.
    Helzlsouer, Kathy J.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Kaaks, Rudolph
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Merritt, Melissa
    Onland-Moret, Charlotte
    Rinaldi, Sabina
    Sanchez, Maria-Jose
    Sieri, Sabina
    Schock, Helena
    Shu, Xiao-Ou
    Sluss, Patrick M.
    Staats, Paul N.
    Travis, Ruth C.
    Tjonneland, Anne
    Trichopoulou, Antonia
    Tworoger, Shelley
    Visvanathan, Kala
    Krogh, Vittorio
    Weiderpass, Elisabete
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Dorgan, Joanne F.
    Demographic, lifestyle, and other factors in relation to antimullerian hormone levels in mostly late premenopausal women2017In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 107, no 4Article in journal (Refereed)
    Abstract [en]

    Objective: To identify reproductive, lifestyle, hormonal, and other correlates of circulating antimullerian hormone (AMH) concentrations in mostly late premenopausal women. Design: Cross-sectional study. Setting: Not applicable. Patient(s): A total of 671 premenopausal women not known to have cancer. Intervention(s): None. Main Outcome Measure(s): Concentrations of AMH were measured in a single laboratory using the picoAMH ELISA. Multivariable-adjusted median (and interquartile range) AMH concentrations were calculated using quantile regression for several potential correlates. Result(s): Older women had significantly lower AMH concentrations (>= 40 [n = 444] vs. < 35 years [n = 64], multivariable-adjusted median 0.73 ng/mL vs. 2.52 ng/mL). Concentrations of AMH were also significantly lower among women with earlier age at menarche (< 12 [n = 96] vs. >= 14 years [n = 200]: 0.90 ng/mL vs. 1.12 ng/mL) and among current users of oral contraceptives (n = 27) compared with never or former users (n = 468) (0.36 ng/mL vs. 1.15 ng/mL). Race, body mass index, education, height, smoking status, parity, and menstrual cycle phase were not significantly associated with AMH concentrations. There were no significant associations between AMH concentrations and androgen or sex hormone-binding globulin concentrations or with factors related to blood collection (e.g., sample type, time, season, and year of blood collection). Conclusion(s): Among premenopausal women, lower AMH concentrations are associated with older age, a younger age at menarche, and currently using oral contraceptives, suggesting these factors are related to a lower number or decreased secretory activity of ovarian follicles.

  • 55. Kaaks, Rudolf
    et al.
    Fortner, Renée Turzanski
    Hüsing, Anika
    Barrdahl, Myrto
    Hopper, Marika
    Johnson, Theron
    Tjønneland, Anne
    Hansen, Louise
    Overvad, Kim
    Fournier, Agnès
    Boutron-Ruault, Marie-Christine
    Kvaskoff, Marina
    Dossus, Laure
    Johansson, Mattias
    Boeing, Heiner
    Trichopoulou, Antonia
    Benetou, Vassiliki
    La Vecchia, Carlo
    Sieri, Sabina
    Mattiello, Amalia
    Palli, Domenico
    Tumino, Rosario
    Matullo, Giuseppe
    Onland-Moret, N. Charlotte
    Gram, Inger T.
    Weiderpass, Elisabete
    Sánchez, Maria-Jose
    Navarro Sanchez, Carmen
    Duell, Eric J.
    Ardanaz, Eva
    Larranaga, Nerea
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Jirström, Karin
    Nodin, Björn
    Travis, Ruth C.
    Riboli, Elio
    Merritt, Melissa
    Aune, Dagfinn
    Terry, Kathryn
    Cramer, Daniel W.
    Anderson, Karen S.
    Tumor-associated autoantibodies as early detection markers for ovarian cancer?: A prospective evaluation2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 3, p. 515-526Article in journal (Refereed)
    Abstract [en]

    Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times 6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited. What's new? Could autoantibodies against tumor antigens provide an early warning system for ovarian cancer? These authors tested how well certain antibodies detected ovarian cancer. They selected four candidate antibodies, to p53, CTAG1A, CTAG2 and NUDT11 proteins, which appear in elevated levels in cancer patients. None of them performed well as a herald of burgeoning cancer. They did not perform any better than the best currently available biomarker, CA125, and as lead times increased past 6 months prediagnosis, the effectiveness diminished. Surprisingly, elevated antibodies appeared in quite a few of the control samples, suggesting they might not be as cancer-specific as expected.

  • 56.
    Labani-Motlagh, Alireza
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Israelsson, Pernilla
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nagaev, Ivan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Nagaeva, Olga
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Dehlin, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Baranov, Vladimir
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Mincheva-Nilsson, Lucia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity2016In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 37, no 4, p. 5455-5466Article in journal (Refereed)
    Abstract [en]

    Cancers constitutively produce and secrete into the blood and other biofluids 30-150 nm-sized endosomal vehicles called exosomes. Cancer-derived exosomes exhibit powerful influence on a variety of biological mechanisms to the benefit of the tumors that produce them. We studied the immunosuppressive ability of epithelial ovarian cancer (EOC) exosomes on two cytotoxic pathways of importance for anticancer immunity-the NKG2D receptor-ligand pathway and the DNAM-1-PVR/nectin-2 pathway. Using exosomes, isolated from EOC tumor explant and EOC cell-line culture supernatants, and ascitic fluid from EOC patients, we studied the expression of NKG2D and DNAM-1 ligands on EOC exosomes and their ability to downregulate the cognate receptors. Our results show that EOC exosomes differentially and constitutively express NKG2D ligands from both MICA/B and ULBP families on their surface, while DNAM-1 ligands are more seldom expressed and not associated with the exosomal membrane surface. Consequently, the NKG2D ligand-bearing EOC exosomes significantly downregulated the NKG2D receptor expression on peripheral blood mononuclear cells (PBMC) while the DNAM-1 receptor was unaffected. The downregulation of NKG2D receptor expression was coupled to inhibition of NKG2D receptor-ligand-mediated degranulation and cytotoxicity measured in vitro with OVCAR-3 and K562 cells as targets. The EOC exosomes acted as a decoy impairing the NKG2D mediated cytotoxicity while the DNAM-1 receptor-ligand system remained unchanged. Taken together, our results support and explain the mechanism behind the recently reported finding that in EOC, NK-cell recognition and killing of tumor cells was mainly dependent on DNAM-1 signaling while the contribution of the NKG2D receptor-ligand pathway was complementary and uncertain.

  • 57. Lahmann, Petra H
    et al.
    Cust, Anne E
    Friedenreich, Christine M
    Schulz, Mandy
    Lukanova, Annekatrin
    Kaaks, Rudolf
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tjønneland, Anne
    Halkjaer, Jytte
    Severinsen, Marianne Tang
    Overvad, Kim
    Fournier, Agnès
    Chabbert-Buffet, Nathalie
    Clavel-Chapelon, Françoise
    Dossus, Laure
    Pischon, Tobias
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Naska, Androniki
    Palli, Domenico
    Grioni, Sara
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Redondo, María-Luisa
    Jakszyn, Paula
    Sánchez, María-José
    Tormo, María-José
    Ardanaz, Eva
    Arriola, Larraitz
    Manjer, Jonas
    Jirström, Karin
    Bueno-de-Mesquita, H Bas
    May, Anne M
    Peeters, Petra HM
    Onland-Moret, N Charlotte
    Bingham, Sheila
    Khaw, Kay-Tee
    Allen, Naomi E
    Spencer, Elizabeth
    Rinaldi, Sabina
    Slimani, Nadia
    Chajes, Véronique
    Michaud, Dominique
    Norat, Teresa
    Riboli, Elio
    Anthropometric measures and epithelial ovarian cancer risk in the European prospective investigation into cancer and nutrition2010In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 126, no 10, p. 2404-2415Article in journal (Refereed)
    Abstract [en]

    We examined the associations of measured anthropometric factors, including general and central adiposity and height, with ovarian cancer risk. We also investigated these associations by menopausal status and for specific histological subtypes. Among 226,798 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, there were 611 incident cases of primary, malignant, epithelial ovarian cancer diagnosed during a mean 8.9 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. Compared to women with body mass index (BMI) < 25 kg/m2, obesity (BMI > or = 30 kg/m2) was associated with excess ovarian cancer risk for all women combined (HR = 1.33, 95% CI = 1.05-1.68; p(trend) = 0.02) and postmenopausal women (HR = 1.59, 95% CI = 1.20-2.10; p(trend) = 0.001), but the association was weaker for premenopausal women (HR = 1.16, 95% CI = 0.65-2.06; p(trend) = 0.65). Neither height or weight gain, nor BMI-adjusted measures of fat distribution assessed by waist circumference, waist-hip ratio (WHR) or hip circumference were associated with overall risk. WHR was related to increased risk of mucinous tumors (BMI-adjusted HR per 0.05 unit increment = 1.17, 95% CI = 1.00-1.38). For all women combined, no other significant associations with risk were observed for specific histological subtypes. This large, prospective study provides evidence that obesity is an important modifiable risk factor for epithelial ovarian cancer, particularly among postmenopausal women.

  • 58. Liu, Lian
    et al.
    Rajareddy, Singareddy
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Reddy, Pradeep
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Jagarlamudi, Krishna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Du, Chun
    Shen, Yan
    Guo, Yongzhi
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Boman, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lundin, Eva
    Patologi.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Selstam, Gunnar
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Liu, Kui
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Phosphorylation and inactivation of glycogen synthase kinase-3 by soluble kit ligand in mouse oocytes during early follicular development.2007In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 38, no 1-2, p. 137-146Article in journal (Refereed)
    Abstract [en]

    Communication between mammalian oocytes and their surrounding granulosa cells through the Kit-Kit ligand (KL, or stem cell factor, SCF) system has been shown to be crucial for follicular development. Our previous studies (Reddy et al. 2005, Liu et al. 2006) have indicated that the intra-oocyte KL-Kit-PI3 kinase (PI3K)-Akt-Foxo3a cascade may play an important role in follicular activation and early development. In the present study, using in situ hybridization and in vitro culture of growing oocytes from 8-day-old postnatal mice, we have demonstrated that another Akt substrate, glycogen synthase kinase-3 (GSK-3), is expressed in growing oocytes. Also, treatment of cultured mouse oocytes with soluble KL not only leads to increased Akt kinase activity in the oocytes, which can phosphorylate recombinant GSK-3 in vitro, but also leads to phosphorylation of oocyte GSK-3alpha and GSK-3beta, which can result in the inactivation of GSK-3 function in oocytes. In addition, we have shown that the regulation of GSK-3alpha and GSK-3beta in cultured oocytes by soluble KL is accomplished through PI3K, since the PI3K-specific inhibitor LY294002 completely abolished the KL-induced phosphorylation of GSK-3alpha and GSK-3beta. Moreover, blockage of the Kit signaling pathway by a Kit function-blocking antibody, ACK2, resulted in reduced phosphorylation of GSK-3. Taken together, our data suggest that the cascade from granulosa cell-derived KL to Kit-PI3K-Akt-GSK-3 in oocytes may take part in regulation of oocyte growth and early ovarian follicular development.

  • 59. Lukanova, Annekatrin
    et al.
    Andersson, Ritu
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wulff, Marianne
    Zeleniuch-Jacquotte, Anne
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Dossus, Laure
    Afanasyeva, Yelena
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Arslan, Alan A
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Human chorionic gonadotropin and alpha-fetoprotein concentrations in pregnancy and maternal risk of breast cancer: a nested case-control study.2008In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 168, no 11, p. 1284-1291Article in journal (Refereed)
    Abstract [en]

    Pregnancy hormones are believed to be involved in the protection against breast cancer conferred by pregnancy. The authors explored the association of maternal breast cancer with human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP). In 2001, a case-control study was nested within the Northern Sweden Maternity Cohort, an ongoing study in which blood samples have been collected from first-trimester pregnant women since 1975. Cases (n = 210) and controls (n = 357) were matched for age, parity, and date of blood donation. Concentrations of hCG and AFP were measured by immunoassay. No overall significant association of breast cancer with either hCG or AFP was observed. However, women with hCG levels in the top tertile tended to be at lower risk of breast cancer than women with hCG levels in the lowest tertile in the whole study population and in subgroups of age at sampling, parity, and age at cancer diagnosis. A borderline-significant decrease in risk with high hCG levels was observed in women who developed breast cancer after the median lag time to cancer diagnosis (> or =14 years; odds ratio = 0.53, 95% confidence interval: 0.27, 1.03; P = 0.06). These findings, though very preliminary, are consistent with a possible long-term protective association of breast cancer risk with elevated levels of circulating hCG in the early stages of pregnancy.

  • 60.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Akhmedkhanov, Arslan
    Micheli, Andrea
    Rinaldi, Sabina
    Zeleniuch-Jacquotte, Anne
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Muti, Paola
    Biessy, Carine
    Krogh, Vittorio
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Riboli, Elio
    Kaaks, Rudolf
    Toniolo, Paolo
    Circulating levels of sex steroid hormones and risk of ovarian cancer.2003In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 104, no 5, p. 636-642Article in journal (Refereed)
    Abstract [en]

    Experimental and epidemiological evidence supports a role for sex steroid hormones in the pathogenesis of ovarian cancer. We investigated the association between ovarian cancer risk and pre-diagnostic blood concentrations of testosterone, androstenedione, DHEAS, estrone and SHBG. A case-control study nested within 3 cohorts, in New York (USA), Umeå (Sweden) and Milan (Italy), included 132 subjects with primary invasive epithelial ovarian cancer. For each case subject, 2 controls were selected who matched a case on cohort, menopausal status, age and date of recruitment and, if premenopausal, day of the menstrual cycle at blood donation. Only women who did not use exogenous hormones at blood donation were included in the study. Conditional logistic regression was used to relate cancer risk to sex steroid hormone concentrations with adjustment for potential confounders. No clear association was observed between ovarian cancer risk and any of the 5 hormones under study. In the premenopausal group, the risk appeared to increase with increasing blood concentrations of androstenedione (upper vs. lower tertile OR = 2.35; 95% CI = 0.81-6.82.), but the small number of subjects in the sub-group precluded reaching unambiguous conclusions about such association. Our study does not support previous observations relating elevations in blood levels of the major sex steroid hormones to an increased risk of ovarian cancer, but offers some evidence that elevated circulating androstenedione before menopause may be associated with increased ovarian cancer risk.

  • 61.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Micheli, Andrea
    Akhmedkhanov, Arslan
    Rinaldi, Sabina
    Muti, Paola
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Biessy, Carine
    Krogh, Vittorio
    Riboli, Elio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Berrino, Franco
    Zeleniuch-Jacquotte, Anne
    Toniolo, Paolo
    Kaaks, Rudolf
    Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy).2003In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 14, no 3, p. 285-292Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the association of prediagnostic circulating levels of C-peptide, as a marker of pancreatic insulin secretion, and IGF binding proteins -1 and -2, as indicators of the biologically active IGF-I concentration, with risk of developing ovarian cancer. METHODS: The study was nested within three prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Case subjects were 132 women with primary invasive epithelial ovarian cancer diagnosed at least one year after blood donation. For each case, two control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. RESULTS: Odds ratios and their 95% confidence intervals for risk of developing ovarian cancer over quartiles of peptides concentrations after adjustment for BMI and fasting were: 1.00, 0.66 (0.35-1.23), 0.96 (0.51-1.82) and 0.89 (0.44-1.81) for C-peptide; 1.00, 1.10 (0.58-2.09), 1.07 (0.55-2.04) and 0.79 (0.38-1.62) for IGFBP-1; and 1.00, 1.01 (0.54-1.89), 0.98 (0.51-1.88) and 0.87 (0.45-1.68) for IGFBP-2. In women who had ovarian cancer diagnosis before age 55 the ORs for the top tertiles of IGFBP-1 and IGFBP-2 were 0.51 (0.18-1.49) and 0.53 (0.18-1.54), respectively. CONCLUSIONS: This study does not support an independent direct etiological role of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before age 55.

  • 62.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Micheli, Andrea
    Arslan, Alan
    Ferrari, Pietro
    Rinaldi, Sabina
    Krogh, Vittorio
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shore, Roy E
    Biessy, Carine
    Muti, Paola
    Riboli, Elio
    Koenig, Karen L
    Levitz, Mortimer
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Kaaks, Rudolf
    Toniolo, Paolo
    Zeleniuch-Jacquotte, Anne
    Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women.2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 108, no 3, p. 425-432Article in journal (Refereed)
    Abstract [en]

    Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis.

  • 63.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Toniolo, Paolo
    Micheli, Andrea
    Akhmedkhanov, Arslan
    Rinaldi, Sabina
    Muti, Paola
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Biessy, Carine
    Krogh, Vittorio
    Zeleniuch-Jacquotte, Anne
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Riboli, Elio
    Kaaks, Rudolf
    Circulating levels of insulin-like growth factor-I and risk of ovarian cancer.2002In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 101, no 6, p. 549-554Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor (IGF)-I, a mitogenic and anti-apoptotic peptide, has been implicated in the development of several cancers. We hypothesized that high circulating IGF-I concentrations may be associated with an increased risk of ovarian cancer. A case-control study was nested within 3 prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). One hundred thirty-two women with primary invasive epithelial ovarian cancer diagnosed at least 1 year after blood donation were case subjects. For each case, 2 control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. There was no association between IGF-I concentrations and ovarian cancer risk in the study group as a whole. In analyses restricted to subjects who had developed ovarian cancer at a young age (<55), circulating IGF-I was directly and strongly associated with ovarian cancer risk (OR = 4.97; 95% CI = 1.22-20.2 for the top vs. the bottom IGF-I tertile after adjustment for parity, BMI categories and smoking). There was no significant association of IGF binding protein-3 with ovarian cancer risk. We found a strong direct relationship between circulating IGF-I levels and risk of developing ovarian cancer before age 55. Additional, larger studies of this association are needed to provide more precise estimates of effect.

  • 64.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zeleniuch-Jacquotte, A
    Muti, P
    Mure, A
    Rinaldi, S
    Dossus, L
    Micheli, A
    Arslan, A
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shore, R E
    Krogh, V
    Koenig, K L
    Riboli, E
    Berrino, F
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Toniolo, P
    Kaaks, R
    Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.2004In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 150, no 2, p. 161-171Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

  • 65. Lukanova, Annekatrin
    et al.
    Surcel, Helja-Marja
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Kaasila, Marjo
    Lakso, Hans-Ake
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Schock, Helena
    Husing, Anika
    Kaaks, Rudolf
    Koskela, Pentti
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Pukkala, Eero
    Zeleniuch-Jacquotte, Anne
    Lehtinen, Matti
    Toniolo, Paolo
    Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 4, p. 910-920Article in journal (Refereed)
    Abstract [en]

    Pregnancy reduces maternal risk of breast cancer in the long term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case-control study (536 cases and 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (+/- 6 months) and date of sampling (+/- 3 months) were selected. Estradiol, estrone and progesterone in first-trimester serum were measured by high-performance liquid chromatography tandem mass spectrometry and sex-hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.083.06), but inversely associated with risk in women who were diagnosed =age 40 (upper quartile OR, 0.64; CI, 0.401.04), pinteraction 0.004. Risk estimates for estrone mirrored those for estradiol but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40.

  • 66.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Zeleniuch-Jacquotte, Anne
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Arslan, Alan A
    Afanasyeva, Yelena
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. null.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. null.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. null.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. null.
    Insulin-like growth factor I in pregnancy and maternal risk of breast cancer2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 12, p. 2489-2493Article in journal (Refereed)
    Abstract [en]

    Background: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy.

    Methods: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI).

    Results: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II.

    Conclusions: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy.

  • 67.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zeleniuch-Jacquotte, Anne
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Micheli, Andrea
    Arslan, Alan A
    Rinaldi, Sabina
    Muti, Paola
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Koenig, Karen L
    Biessy, Carine
    Krogh, Vittorio
    Riboli, Elio
    Shore, Roy E
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Kaaks, Rudolf
    Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 108, no 2, p. 262-268Article in journal (Refereed)
    Abstract [en]

    Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.

  • 68.
    Lundin, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dossus, Laure
    Clendenen, Tess
    Krogh, Vittorio
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sieri, Sabina
    Arslan, Alan
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Zeleniuch-Jacquotte, Anne
    Toniolo, Paolo
    Lukanova, Annekatrin
    C-reactive protein and ovarian cancer: a prospective study nested in three cohorts (Sweden, USA, Italy).2009In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 20, no 7, p. 1151-1159Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Inflammatory processes may influence the risk of epithelial ovarian cancer, but available epidemiological evidence is limited and indirect. Circulating C-reactive protein (CRP), a sensitive marker of inflammation, may serve as a direct biological marker of an underlying association. METHODS: The association between ovarian cancer risk and pre-diagnostic circulating CRP was tested in a case-control study nested within three prospective cohorts from Sweden, USA, and Italy. The study included 237 cases and 427 individually matched controls. CRP was measured in stored blood samples by high-sensitivity immunoturbidimetric assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. RESULTS: Overall, CRP was not related to risk of ovarian cancer. However, a marked increase in risk was observed for CRP concentrations >10 mg/l: OR (95% CI) 4.4 (1.8-10.9), which remained significant after limiting analyses to cases diagnosed more than two or five years after blood donation (OR 3.0 (1.2-8.0) and 3.6 (1.0-13.2), respectively). Risk of mucinous tumors increased with high CRP, but the number of cases in this analysis was small. CONCLUSION: Study results offer additional support to the concept that chronic inflammation plays a role in epithelial ovarian cancer.

  • 69.
    Lundin, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wirgin, Isaac
    Lukanova, Annekatrin
    Afanasyeva, Yelena
    Krogh, Vittorio
    Axelsson, Tomas
    Hemminki, Kari
    Clendenen, Tess V
    Arslan, Alan A
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sieri, Sabina
    Roy, Nirmal
    Koenig, Karen L
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Berrino, Franco
    Toniolo, Paolo
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Försti, Asta
    Muti, Paola
    Lenner, Per
    Shore, Roy E
    Zeleniuch-Jacquotte, Anne
    Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer2012In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 36, no 5, p. 445-452Article in journal (Refereed)
    Abstract [en]

    Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.

  • 70.
    Lundin, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lairon, D
    Tidehag, P
    Aman, P
    Adlercreutz, H
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Effects of meal frequency and high-fibre rye-bread diet on glucose and lipid metabolism and ileal excretion of energy and sterols in ileostomy subjects.2004In: European Journal of Clinical Nutrition, ISSN 0954-3007, Vol. 58, no 10, p. 1410-9Article in journal (Refereed)
  • 71. Merritt, Melissa A
    et al.
    Riboli, Elio
    Murphy, Neil
    Kadi, Mai
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Dossus, Laure
    Dartois, Laureen
    Clavel-Chapelon, Françoise
    Fortner, Renée T
    Katzke, Verena A
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H
    Lund, Eiliv
    Nakamura, Aurelie
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Molina-Montes, Esther
    Larrañaga, Nerea
    Dorronsoro, Miren
    Cirera, Lluís
    Barricarte, Aurelio
    Olsson, Åsa
    Butt, Salma
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wareham, Nicholas J
    Key, Timothy J
    Brennan, Paul
    Ferrari, Pietro
    Wark, Petra A
    Norat, Teresa
    Cross, Amanda J
    Gunter, Marc J
    Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition: a cohort study2015In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 13, article id 252Article in journal (Refereed)
    Abstract [en]

    Background: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. Methods: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled > 500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. Results: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (>= 15 years versus < 12; 0.90; 0.85-0.96; P for trend = 0.038). Conclusions: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.

  • 72. Merritt, Melissa A.
    et al.
    Riboli, Elio
    Weiderpass, Elisabete
    Tsilidis, Konstantinos K.
    Overvad, Kim
    Tjønneland, Anne
    Hansen, Louise
    Dossus, Laure
    Fagherazzi, Guy
    Baglietto, Laura
    Fortner, Renee T.
    Ose, Jennifer
    Steffen, Annika
    Boeing, Heiner
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Lagiou, Pagona
    Masala, Giovanna
    Sieri, Sabina
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, H. B(as)
    Onland-Moret, N. Charlotte
    Peeters, Petra H.
    Hjartåker, Anette
    Gram, Inger Torhild
    Ramon Quiros, J.
    Obon-Santacana, Mireia
    Molina-Montes, Esther
    Huerta Castano, Jose Maria
    Ardanaz, Eva
    Chamosa, Saioa
    Sonestedt, Emily
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C.
    Rinaldi, Sabina
    Romieu, Isabelle
    Chajes, Veronique
    Gunter, Marc J.
    Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition2014In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 38, no 5, p. 528-537Article in journal (Refereed)
    Abstract [en]

    There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n = 1095) and borderline (n = 96) EOC. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariate models, we observed no association with consumption of total fat, animal or plant fat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was, however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) of polyunsaturated fat (HR = 1.22, 95% CI = 1.02-1.48, P-trend = 0.02). We did not observe heterogeneity in the risk associations in comparisons of serous and endometrioid histologic subtypes. This study does not support an etiological role for total fat intake in relation to EOC risk; however, based on observations of a positive association between intake of polyunsaturated fat and invasive EOC risk in the current and previous studies, this fat subtype warrants further investigation to determine its potential role in EOC development. 

  • 73. Merritt, Melissa A.
    et al.
    Tzoulaki, Joanna
    van den Brandt, Piet A.
    Schouten, Leo J.
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Patel, Chirag J.
    Tjonneland, Anne
    Hansen, Louise
    Overvad, Kim
    His, Mathilde
    Dartois, Laureen
    Boutron-Ruault, Marie-Christine
    Fortner, Renee T.
    Kaaks, Rudolf
    Aleksandrova, Krasimira
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Bamia, Christina
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Ricceri, Fulvio
    Mattiello, Amalia
    Bueno-de-Mesquita, H. Bas
    Onland-Moret, N. Charlotte
    Peeters, Petra H.
    Skeie, Guri
    Jareid, Mie
    Quiros, J. Ramon
    Obon-Santacana, Mireia
    Sanchez, Maria-Jose
    Chamosa, Saioa
    Huerta, Jose M.
    Barricarte, Aurelio
    Dias, Joana A.
    Sonestedt, Emily
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wareham, Nicholas J.
    Khaw, Kay-Tee
    Travis, Ruth C.
    Ferrari, Pietro
    Riboli, Elio
    Gunter, Marc J.
    Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study2016In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 103, no 1, p. 161-167Article in journal (Refereed)
    Abstract [en]

    Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk.

    Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort.

    Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs.

    Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41).

    Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.

  • 74. Obon-Santacana, Mireia
    et al.
    Lujan-Barroso, Leila
    Travis, Ruth C.
    Freisling, Heinz
    Ferrari, Pietro
    Severi, Gianluca
    Baglietto, Laura
    Boutron-Ruault, Marie-Christine
    Fortner, Renee T.
    Ose, Jennifer
    Boeing, Heiner
    Menendez, Virginia
    Sanchez-Cantalejo, Emilio
    Chamosa, Saioa
    Huerta Castano, Jose Maria
    Ardanaz, Eva
    Khaw, Kay-Tee
    Wareham, Nick
    Merritt, Melissa A.
    Gunter, Marc J.
    Trichopoulou, Antonia
    Papatesta, Eleni-Maria
    Klinaki, Eleni
    Saieva, Calogero
    Tagliabue, Giovanna
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Bueno-de-Mesquita, H. B.
    Peeters, Petra H.
    Onland-Moret, N. Charlotte
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Weiderpass, Elisabete
    Vesper, Hubert W.
    Riboli, Elio
    Duell, Eric J.
    Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer: A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort2016In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 25, no 1, p. 127-134Article in journal (Refereed)
    Abstract [en]

    Background: Acrylamide was classified as “probably carcinogenic to humans (group 2A)” by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case–control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent.

    Methods: A nested case–control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk.

    Results: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96–3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94–3.83, respectively); however, no linear dose–response trends were observed.

    Conclusion: This EPIC nested case–control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC.

    Impact: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk.

  • 75. Obon-Santacana, Mireia
    et al.
    Peeters, Petra H. M.
    Freisling, Heinz
    Dossus, Laure
    Clavel-Chapelon, Francoise
    Baglietto, Laura
    Schock, Helena
    Fortner, Renee T.
    Boeing, Heiner
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Menendez, Virginia
    Sanchez, Maria-Jose
    Larranaga, Nerea
    Huerta Castano, Jose Mara
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C.
    Merritt, Melissa A.
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Orfanos, Philippos
    Masala, Giovanna
    Sieri, Sabina
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Bueno-de-Mesquita, H. B.
    Onland-Moret, N. Charlotte
    Wirfalt, Elisabeth
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Clinical Sciences, Nutrition Epidemiology, Lund University, Malmö, Sweden.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Skeie, Guri
    Gram, Inger T.
    Weiderpass, Elisabete
    Riboli, Elio
    Duell, Eric J.
    Dietary Intake of Acrylamide and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort2015In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 24, no 1, p. 291-297Article in journal (Refereed)
    Abstract [en]

    Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 mu g/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 mu g/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10 mu(g/d), 1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.

  • 76. Obón-Santacana, Mireia
    et al.
    Freisling, Heinz
    Peeters, Petra H
    Lujan-Barroso, Leila
    Ferrari, Pietro
    Boutron-Ruault, Marie-Christine
    Mesrine, Sylvie
    Baglietto, Laura
    Turzanski-Fortner, Renee
    Katzke, Verena A
    Boeing, Heiner
    Quirós, J Ramón
    Molina-Portillo, Elena
    Larrañaga, Nerea
    Chirlaque, María-Dolores
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C
    Merritt, Melissa A
    Gunter, Marc J
    Trichopoulou, Antonia
    Lagiou, Pagona
    Naska, Androniki
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Fiano, Valentina
    Galassom, Rocco
    Bueno-de-Mesquita, H B As
    Onland-Moret, N Charlotte
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Weiderpass, Elisabete
    Vesper, Hubert
    Riboli, Elio
    Duell, Eric J
    Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: a nested case-control study in nonsmoking postmenopausal women from the EPIC cohort2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 5, p. 1129-1138Article in journal (Refereed)
    Abstract [en]

    Acrylamide, classified in 1994 by IARC as "probably carcinogenic to humans," was discovered in 2002 in some heat-treated, carbohydrate-rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case-control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non-smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type-I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HRHbAA;Q5vsQ1 : 0.84, 95%CI: 0.49-1.48; HRHbGA;Q5vsQ1 : 0.94, 95%CI: 0.54-1.63) or type-I EC risk. Additionally, none of the subgroups investigated (BMI < 25 vs. ≥25 kg m(-2) , alcohol drinkers vs. never drinkers, oral contraceptive users vs. non-users) demonstrated effect measure modification. Hemoglobin adducts of acrylamide or glycidamide were not associated with EC or type-I EC risk in 768 nonsmoking postmenopausal women from the EPIC cohort.

  • 77. Ohrvik, Veronica E
    et al.
    Büttner, Barbara E
    Rychlik, Michael
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Witthöft, Cornelia M
    Folate bioavailability from breads and a meal assessed with a human stable-isotope area under the curve and ileostomy model2010In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, no 3, p. 532-538Article in journal (Refereed)
    Abstract [en]

    Our data confirm differences in plasma absorption kinetics for reduced folates and synthetic folic acid administered with the test foods. Stomal folate contents indicated almost complete bioavailability of labeled folate from the breads or breakfast meal.

  • 78. Ose, J.
    et al.
    Fortner, R. T.
    Schock, H.
    Peeters, P. H.
    Onland-Moret, N. C.
    Bueno-de-Mesquita, H. B.
    Weiderpass, E.
    Gram, I. T.
    Overvad, K.
    Tjonneland, A.
    Dossus, L.
    Fournier, A.
    Baglietto, L.
    Trichopoulou, A.
    Benetou, V.
    Trichopoulos, D.
    Boeing, H.
    Masala, G.
    Krogh, V.
    Matiello, A.
    Tumino, R.
    Popovic, M.
    Obon-Santacana, M.
    Larranaga, N.
    Ardanaz, E.
    Sanchez, M-J
    Menendez, V.
    Chirlaque, M-D
    Travis, R. C.
    Khaw, K-T
    Braendstedt, J.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rinaldi, S.
    Kuhn, E.
    Romieu, I.
    Gunter, M. J.
    Merritt, M. A.
    Riboli, E.
    Kaaks, R.
    Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort2015In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, no 1, p. 162-166Article in journal (Refereed)
    Abstract [en]

    Background: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n = 565 cases). Multivariable conditional logistic regression models were used to estimate associations. Results: We observed no association between IGF-I and EOC overall or by tumour characteristics. Conclusions: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.

  • 79. Ose, Jennifer
    et al.
    Fortner, Renée T.
    Rinaldi, Sabina
    Schock, Helena
    Overvad, Kim
    Tjonneland, Anne
    Hansen, Louise
    Dossus, Laure
    Fournier, Agnes
    Baglietto, Laura
    Romieu, Isabelle
    Kuhn, Elisabetta
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Masala, Giovanna
    Sieri, Sabina
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Ramon Quiros, Jose
    Obón-Santacana, Mireia
    Larrañaga, Nerea
    Chirlaque, María-Dolores
    Sánchez, María-José
    Barricarte, Aurelio
    Peeters, Petra H.
    Bueno-de-Mesquita, H. B(as)
    Onland-Moret, N. Charlotte
    Brändstedt, Jenny
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Weiderpass, Elisabete
    Gram, Inger T.
    Lund, Eiliv
    Kaw, Kay-Tee
    Travis, Ruth C.
    Merritt, Melissa A.
    Gunther, Marc J.
    Riboli, Elio
    Kaaks, Rudolf
    Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 2, p. 399-410Article in journal (Refereed)
    Abstract [en]

    The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2=0.79, 95% confidence interval [CI]=[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2=1.99 [0.98-4.06]; high grade: ORlog2=0.75 [0.61-0.93], p(het)0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. What's new? There appear to be several types of epithelial invasive ovarian cancer (EOC), and hormone-related risk factors are poorly understood. In this study, the authors found that the impact of endogenous androgens on the risk of developing EOC differed depending upon tumor characteristics. Androgen concentrations were positively associated with the risk of low-grade and type-I carcinomas, but the study found an inverse association for high-grade tumors. These findings support a possible role for androgens in ovarian carcinogenesis, and emphasize the need for additional research.

  • 80. Ose, Jennifer
    et al.
    Schock, Helena
    Tjonneland, Anne
    Hansen, Louise
    Overvad, Kim
    Dossus, Laure
    Clavel-Chapelon, Francoise
    Baglietto, Laura
    Boeing, Heiner
    Trichopolou, Antonia
    Benetou, Vassiliki
    Lagiou, Pagona
    Masala, Giovanna
    Tagliabue, Giovanna
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Bueno-de-Mesquita, H. B(As)
    Peeters, Petra H. M.
    Onland-Moret, N. Charlotte
    Weiderpass, Elisabete
    Gram, Inger T.
    Sanchez, Soledad
    Obon-Santacana, Mireia
    Sanchez-Perez, Maria-Jose
    Larranaga, Nerea
    Huerta Castano, Jose Mara
    Ardanaz, Eva
    Brandstedt, Jenny
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Travis, Ruth C.
    Khaw, Kay-Tee
    Rinaldi, Sabina
    Romieu, Isabelle
    Merritt, Melissa A.
    Gunter, Marc J.
    Riboli, Elio
    Kaaks, Rudolf
    Fortner, Renee T.
    Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort2015In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 24, no 6, p. 951-961Article in journal (Refereed)
    Abstract [en]

    Background: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP <= 1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist <= 80: ORlog2, 0.97 (0.81-1.16); waist >88: ORlog2, 1.78 (1.28-2.48), P-heterogeneity <= 0.01]. Conclusions: Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity. Impact: Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.

  • 81. Peeters, Petra H M
    et al.
    Lukanova, Annekatrin
    Allen, Naomi
    Berrino, Franco
    Key, Tim
    Dossus, Laure
    Rinaldi, Sabina
    van Gils, Carla H
    Bueno-de-Mesquita, H Bas
    Boeing, Heiner
    Schulz, Mandy
    Chang-Claude, Jenny
    Linseisen, Jakob
    Panico, Salvatore
    Sacerdote, Carlotta
    Palli, Domenico
    Tumino, Rosario
    Trichopoulou, Antonia
    Trichopolos, Dimitrios
    Bamia, Christina
    Larranaga, Nerea
    Ardanaz, Eva
    Pera, Guillem
    Quirós, J Ramón
    Martínez-García, Carmen
    Navarro, Carmen
    Bingham, Sheila A
    Khaw, Kay-Tee
    Clavel, Françoise
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Tetsche, Mette S
    Lund, Eiliv
    Lundin, Eva
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Berglund, Göran
    Riboli, Elio
    Kaaks, R
    Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC).2007In: Endocr Relat Cancer, ISSN 1351-0088, Vol. 14, no 1, p. 81-90Article in journal (Refereed)
  • 82.
    Reddy, Pradeep
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Liu, Lian
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ren, Chong
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Lindgren, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Boman, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shen, Yan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Rytinki, Miia
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Liu, Kui
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Formation of E-cadherin-mediated cell-cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells2005In: Mol Endocrinol, ISSN 0888-8809, Vol. 19, no 10, p. 2564-2578Article in journal (Refereed)
  • 83.
    Reddy, Pradeep
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Shen, Lijun
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ren, Chong
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Boman, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lindgren, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Liu, Yi-Xun
    Sun, Qing-Yuan
    Liu, Kui
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development2005In: Dev Biol, ISSN 0012-1606, Vol. 281, no 2, p. 160-170Article in journal (Refereed)
  • 84. Rinaldi, Sabina
    et al.
    Dossus, Laure
    Lukanova, Annekatrin
    Peeters, Petra H M
    Allen, Naomi E
    Key, Timothy
    Bingham, Sheila
    Khaw, Kay-Tee
    Trichopoulos, Dimitrios
    Trichopoulou, Antonia
    Oikonomou, Eleni
    Pera, Guillem
    Larrañaga, Nerea
    Martinez-Garcia, Carmen
    Ardanaz, Eva
    Quirós, J Ramón
    Tormo, María-José
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Chang-Claude, Jenny
    Linseisen, Jakob
    Schulz, Mandy
    Boeing, Heiner
    van Gils, Carla H
    Bueno-de-Mesquita, Bas H
    Pala, Valeria
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Clavel-Chapelon, Françoise
    Mesrine, Sylvie
    Boutron-Ruault, Marie-Christine
    Lundin, Eva
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology. Patologi.
    Ågren, Åsa
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Berglund, Göran
    Manjer, Jonas
    Kumle, Merethe
    Lund, Eiliv
    Slimani, Nadia
    Saracci, Rodolfo
    Riboli, Elio
    Kaaks, Rudolf
    Endogenous androgens and risk of epithelial ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).2007In: Cancer Epidemiol Biomarkers Prev, ISSN 1055-9965, Vol. 16, no 1, p. 23-9Article in journal (Refereed)
  • 85. Rinaldi, Sabina
    et al.
    Toniolo, Paolo
    Muti, Paola
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Zeleniuch-Jacquotte, Anne
    Arslan, Alan
    Micheli, Andrea
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Onkologi.
    Dossus, Laure
    Krogh, Vittorio
    Shore, Roy E
    Koenig, Karen L
    Riboli, Elio
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lukanova, Annekatrin
    Kaaks, Rudolf
    IGF-I, IGFBP-3 and breast cancer in young women: a pooled re-analysis of three prospective studies2005In: European Journal of Cancer Prevention, ISSN 0959-8278, Vol. 14, no 6, p. 493-496Article in journal (Refereed)
  • 86. Sasamoto, Naoko
    et al.
    Babic, Ana
    Rosner, Bernard A.
    Fortner, Renee T.
    Vitonis, Allison F.
    Yamamoto, Hidemi
    Fichorova, Raina N.
    Tjonneland, Anne
    Hansen, Louise
    Overvad, Kim
    Kvaskoff, Marina
    Fournier, Agnes
    Mancini, Francesca Romana
    Boeing, Heiner
    Trichopoulou, Antonia
    Peppa, Eleni
    Karakatsani, Anna
    Palli, Domenico
    Pala, Valeria
    Mattiello, Amalia
    Tumino, Rosario
    Grasso, Chiara C.
    Onland-Moret, N. Charlotte
    Weiderpass, Elisabete
    Ramon Quiros, J.
    Lujan-Barroso, Leila
    Rodriguez-Barranco, Miguel
    Colorado-Yohar, Sandra
    Barricarte, Aurelio
    Dorronsoro, Miren
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sartor, Hanna
    Khaw, Kay-Tee
    Key, Timothy J.
    Muller, David
    Riboli, Elio
    Gunter, Marc J.
    Dossus, Laure
    Kaaks, Rudolf
    Cramer, Daniel W.
    Tworoger, Shelley S.
    Terry, Kathryn L.
    Predicting Circulating CA125 Levels among Healthy Premenopausal Women2019In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 6, p. 1076-1085Article in journal (Refereed)
    Abstract [en]

    Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (>= 35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.

  • 87.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. German Cancer Research Center, Heidelberg.
    Fortner, Renée T
    German Cancer Research Center, Heidelberg.
    Surcel, Heljä-Marja
    National Institute for Health and Welfare, Oulu, Finland.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Pukkala, Eero
    School of Public Health, University of Tampere, Finland.
    Lehtinen, Matti
    School of Public Health, University of Tampere, Finland.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 2, p. 439-447Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a nonsignificant decrease in risk for invasive [ORT3 vs. T1 : 0.79 (0.62-1.02); ptrend  = 0.07] and endometrioid tumors [ORT3 vs. T1 : 0.55 (0.28-1.07); ptrend  = 0.07]. The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis [ORT3 vs. T1 : 0.74 (0.57-0.96); ptrend  = 0.03]. Our study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC.

  • 88.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Vääräsmäki, M.
    Oulu, Finland.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Fry, A.
    London, UK.
    Dorgan, J. F.
    Baltimore, MD, USA.
    Pukkala, E.
    Helsinki, Finland; Tampere, Finland.
    Lehtinen, M.
    Tampere, Finland.
    Surcel, H. M.
    Oulu, Finland.
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer.
    Anti-Mullerian hormone and risk of invasive serous ovarian cancer2014In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, no 5, p. 583-589Article in journal (Refereed)
    Abstract [en]

    Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer. A case-control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986-2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations. Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49-1.77 for top vs. bottom tertile, P (trend) = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06-2.54) was observed in younger women, P (homogeneity) = 0.002. In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.

  • 89.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
    Surcel, Helja-Marja
    Oulu, Finland.
    Zeleniuch-Jacquotte, Anne
    Umeå University, Faculty of Medicine, Department of Biobank Research. New York, USA.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Fortner, Renee Turzanski
    Heidelberg, Germany.
    Kaaks, Rudolf
    Heidelberg, Germany.
    Pukkala, Eero
    Helsinki, Finland; Tampere, Finland.
    Lehtinen, Matti
    Tampere, Finland.
    Toniolo, Paolo
    New York, USA; Lausanne, Switzerland.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer2014In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 6, p. 831-844Article in journal (Refereed)
    Abstract [en]

    Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E-2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E-2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.

  • 90.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. German Cancer Research Center, Heidelberg, Germany.
    Zeleniuch-Jacquotte, A
    New York University school of medicine, New York, USA.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Surcel, HM
    National Institute for Health and Welfare, Oulu, Finland.
    Fortner, RT
    German Cancer Research Center, Heidelberg, Germany.
    Longitudinal Assessment of Pregnancy HormonesManuscript (preprint) (Other academic)
    Abstract [en]

    Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood. We used serial serum samples from 71 pregnant women (25 primiparous, 25 biparous, and 21 with 2 consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester. Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g. estradiol, 1st vs. 2nd and 2nd vs. 3rd trimester r=0.51 and r=0.60, p<0.01; 1st vs. 3rd trimester r=0.32, p<0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R²T1=16% and R²T2=42%). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones. In conclusion, one hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations.

  • 91.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
    Zeleniuch-Jacquotte, Anne
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Lehtinen, Matti
    Surcel, Heljä-Marja
    Fortner, Renee T.
    Hormone concentrations throughout uncomplicated pregnancies: a longitudinal study2016In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 16, article id 146Article in journal (Refereed)
    Abstract [en]

    Background: Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. Many of the existing maternity and birth cohorts include specimens drawn only once during pregnancy. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood.

    Methods: We used serial serum samples from 71 pregnant women (25 primiparous, 25 multiparous, and 21 with two consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester.

    Results: Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g., estradiol, r(T1 vs. T2) = 0.51 and r(T2 vs. T3) = 0.60, p < 0.01; r(T1 vs. T3) = 0.32, p < 0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R-T1(2) = 16 % and R-T2(2) = 42 %). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones.

    Conclusions: One hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations. Therefore, single hormone measurements available from maternity cohorts are suitable to quantify hormone exposure during pregnancy. To our knowledge, we provide the first data on correlations between hormone concentrations both across trimesters of a single pregnancy, as well as between two subsequent pregnancies.

  • 92. Schulz, Mandy
    et al.
    Lahmann, Petra H
    Boeing, Heiner
    Hoffmann, Kurt
    Allen, Naomi
    Key, Timothy J A
    Bingham, Sheila
    Wirfält, Elisabet
    Berglund, Göran
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lukanova, Annekatrin
    Martínez Garcia, Carmen
    González, Carlos A
    Tormo, Maria J
    Quirós, José R
    Ardanaz, Eva
    Larrañaga, Nerea
    Lund, Eiliv
    Gram, Inger T
    Skeie, Guri
    Peeters, Petra H M
    van Gils, Carla H
    Bueno-de-Mesquita, H Bas
    Büchner, Frederike L
    Pasanisi, Patrizia
    Galasso, Rocco
    Palli, Domenico
    Tumino, Rosario
    Vineis, Paolo
    Trichopoulou, Antonia
    Kalapothaki, Victoria
    Trichopoulos, Dimitrios
    Chang-Claude, Jenny
    Linseisen, Jakob
    Boutron-Ruault, Marie Christine
    Touillaud, Marina
    Clavel-Chapelon, Françoise
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Tetsche, Mette
    Jenab, Mazda
    Norat, Teresa
    Kaaks, Rudolph
    Riboli, Elio
    Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition.2005In: Cancer Epidemiology Biomarkers & Prevention, ISSN 1055-9965, Vol. 14, no 11 Pt 1, p. 2531-5Article in journal (Refereed)
  • 93. Schulz, Mandy
    et al.
    Nöthlings, Ute
    Allen, Naomi
    Onland-Moret, N Charlotte
    Agnoli, Claudia
    Engeset, Dagrun
    Galasso, Rocco
    Wirfält, Elisabet
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Chajes, Veronique
    Clavel-Chapelon, Francoise
    Ray, Jennifer
    Hoffmann, Kurt
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Trichopoulos, Dimitrios
    Georgila, Christina
    Zourna, Pantelina
    Palli, Domenico
    Berrino, Franco
    Tumino, Rosario
    Vineis, Paolo
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Ocké, Marga C
    Peeters, Petra H M
    Lund, Eiliv
    Gram, Inger T
    Skeie, Guri
    Berglund, Göran
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    González, Carlos A
    Quirós, José Ramón
    Dorronsoro, Miren
    Martínez, Carmen
    Tormo, Marie-Jose
    Barricarte, Aurelio
    Bingham, Sheila
    Khaw, Kay-Tee
    Key, Timothy J A
    Jenab, Mazda
    Rinaldi, Sabina
    Slimani, Nadia
    Riboli, Elio
    No association of consumption of animal foods with risk of ovarian cancer.2007In: Cancer Epidemiol Biomarkers Prev, ISSN 1055-9965, Vol. 16, no 4, p. 852-5Article in journal (Refereed)
  • 94.
    Stefansson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Oda, Husam
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öfverman, Charlotte
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    LRIG protein expression and HPV prevalence in vulvar cancer patients in northern Sweden2015In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 25, no 9, p. 684-684Article in journal (Other academic)
  • 95.
    Stefansson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Oda, Husam
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öfverman, Charlotte
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    LRIG1‑2 and LMO7 immunoreactivity in vulvar squamous cell carcinoma: association with prognosis in relation to HPV‑DNA and p16INK4a status2019In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 42, no 1, p. 142-150Article in journal (Refereed)
    Abstract [en]

    The present study was conducted to investigate the possible prognostic value of molecular markers LRIG1‑2 and LIM domain 7 protein (LMO7) in vulvar squamous cell carcinoma (VSCC) and their possible correlation to human papilloma virus (HPV)‑ and p16INK4a‑status of the tumors. Patients diagnosed with VSCC at the University Hospital of Umeå, Sweden, during the years 1990‑2013 were selected. Tumor blocks were retrieved from tissue archives and clinical data were collected from the records of patients. HPV‑PCR analysis, HPV genotyping and immunohistochemistry were performed. In total, 112 patients were included. Forty percent of the tumors were HPV‑positive, 27% were p16INK4a‑positive and 23% were positive for both HPV and p16INK4a (considered HPV‑driven). HPV‑positivity and p16INK4a‑positivity were associated with prolonged disease‑free survival (DFS) in Kaplan‑Meier survival analysis. Leucine‑rich repeats and immunoglobulin‑like domains 1 (LRIG1) immunoreactivity was not significantly associated with survival. High leucine‑rich repeats and immunoglobulin‑like domains 2 (LRIG2) immunoreactivity was associated with a prolonged overall survival (OS) (P=0.001). By analyzing HPV‑negative cases only, it was determined that high LRIG2 immunoreactivity was associated with both favorable OS (P=0.008) and DFS (P=0.031). LRIG2 immunoreactivity was also an independent prognostic factor in multivariate analysis of OS (P=0.002, HR=0.41; 95% CI, 0.24‑0.71). High immunoreactivity with LMO7‑1250 antibody was associated with survival benefits in the whole cohort (OS; P=0.011) although DFS was only prolonged in HPV‑negative and not HPV‑driven tumors (P=0.038 and 0.042, respectively). The present study indicated that LRIG2 and LMO7 may be useful prognostic markers in VSCC, particularly for patients without HPV‑driven tumors or with advanced tumors at diagnosis. In contrast to earlier observations regarding other types of squamous cell carcinoma, LRIG1 was not a significant prognostic factor in VSCC.

  • 96. Terry, Kathryn L.
    et al.
    Schock, Helena
    Fortner, Renée T.
    Hüsing, Anika
    Fichorova, Raina N.
    Yamamoto, Hidemi S.
    Vitonis, Allison F.
    Johnson, Theron
    Overvad, Kim
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Mesrine, Sylvie
    Severi, Gianluca
    Dossus, Laure
    Rinaldi, Sabina
    Boeing, Heiner
    Benetou, Vassiliki
    Lagiou, Pagona
    Trichopoulou, Antonia
    Krogh, Vittorio
    Kuhn, Elisabetta
    Panico, Salvatore
    Bueno-de-Mesquita, H. Bas
    Onland-Moret, N. Charlotte
    Peeters, Petra H.
    Gram, Inger Torhild
    Weiderpass, Elisabete
    Duell, Eric J.
    Sanchez, Maria-Jose
    Ardanaz, Eva
    Etxezarreta, Nerea
    Navarro, Carmen
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jirström, Karin
    Manjer, Jonas
    Wareham, Nicholas J.
    Khaw, Kay-Tee
    Byrne, Karl Smith
    Travis, Ruth C.
    Gunter, Marc J.
    Merritt, Melissa A.
    Riboli, Elio
    Cramer, Daniel W.
    Kaaks, Rudolf
    A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort2016In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 18, p. 4664-4675Article in journal (Refereed)
    Abstract [en]

    Purpose: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate earlydetection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design: We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results: We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases.

  • 97. Tikk, Kaja
    et al.
    Sookthai, Disorn
    Johnson, Theron
    Dossus, Laure
    Clavel-Chapelon, Francoise
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Baglietto, Laura
    Rinaldi, Sabina
    Romieu, Isabelle
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Masala, Giovanna
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Buckland, Genevieve
    Sanchez, Soledad
    Molina-Montes, Esther
    Amiano, Pilar
    Huerta Castano, Jose Maria
    Barricarte, Aurelio
    Bueno-de-Mesquita, H. Bas
    Monninkhof, Evelyn M.
    Onland-Moret, N. Charlotte
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Weider-pass, Elisabete
    Lund, Eiliv
    Waaseth, Marit
    Khaw, Kay-Tee
    Key, Timothy J.
    Travis, Ruth C.
    Gunter, Marc J.
    Riboli, Elio
    Kaaks, Rudolf
    Prolactin Determinants in Healthy Women: A Large Cross-Sectional Study within the EPIC Cohort2014In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, no 11, p. 2532-2542Article in journal (Refereed)
    Abstract [en]

    Background: Experimental and epidemiologic data suggest that higher circulating prolactin is associated with breast cancer risk; however, how various risk factors for breast cancer influence prolactin levels in healthy women is not clear. Methods: We analyzed cross-sectional associations between several suggested reproductive and lifestyle risk factors for breast cancer and circulating prolactin among pre- and postmenopausal women, taking into account the use of current postmenopausal hormone therapy, among 2,560 controls from a breast cancer nested case-control study within the EPIC cohort. Results: Adjusted geometric mean prolactin levels were significantly higher among premenopausal women, and among postmenopausal women using hormone therapy compared with nonusers (8.2, 7.0, and 6.3 ng/mL, respectively; P-cat = <0.0001). Furthermore, prolactin levels were significantly higher among users of combined estrogen-progestin hormone therapy compared with users of estrogen-alone hormone therapy (6.66 vs. 5.90 ng/mL; P-cat = 0.001). Prolactin levels were lower among parous women compared with nulliparous women (8.61 vs. 10.95 ng/mL; P-cat = 0.0002, premenopausal women); the magnitude of this difference depended on the number of full-term pregnancies (22.1% lower, >= 3 vs. 1 pregnancy, P-trend = 0.01). Results for parity were similar but lower in magnitude among postmenopausal women. Prolactin did not vary by other studied factors, with the exception of lower levels among postmenopausal smokers compared with never smokers. Conclusions: Our study shows that current hormone therapy use, especially the use of combined hormone therapy, is associated with higher circulating prolactin levels in postmenopausal women, and confirms prior findings of lower circulating prolactin in parous women. Impact: Our study extends the knowledge linking various breast cancer risk factors with circulating prolactin.

  • 98. Toniolo, Paolo
    et al.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Chen, Tianhui
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schock, Helena
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lehtinen, Matti
    Kaaks, Rudolf
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Zeleniuch-Jacquotte, Anne
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lukanova, Annekatrin
    Human chorionic gonadotropin in pregnancy and maternal risk of breast cancer2010In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 70, no 17, p. 6779-6786Article in journal (Refereed)
    Abstract [en]

    Full-term pregnancies are associated with long-term reductions in maternal risk of breast cancer, but the biological determinants of the protection are unknown. Experimental observations suggest that human chorionic gonadotropin (hCG), a major hormone of pregnancy, could play a role in this association. A case-control study (242 cases and 450 controls) nested within the Northern Sweden Maternity Cohort included women who had donated a blood sample during the first trimester of a first full-term pregnancy. Total hCG was determined on Immulite 2000 analyzer. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. Maternal breast cancer risk decreased with increasing hCG (upper tertile OR, 0.67; CI, 0.46-0.99), especially for pregnancies before age 25 (upper tertile OR, 0.41; CI, 0.21-0.80). The association diverged according to age at diagnosis: risk was reduced after age 40 (upper tertile OR, 0.60; CI, 0.39-0.91) and seemed to increase before age 40 (upper tertile OR, 1.78; CI, 0.72-4.38). Risk was reduced among those diagnosed 10 years or longer after blood draw (upper tertile OR, 0.60; CI, 0.40-0.90), but not so among those diagnosed within 10 years (upper tertile OR, 4.33; CI, 0.86-21.7). These observations suggest that the association between pregnancy hCG and subsequent maternal risk of breast cancer is modified by age at diagnosis. Although the hormone seems to be a determinant of the reduced risk around or after age 50, it might not confer protection against, or it could even increase the risk of, cancers diagnosed in the years immediately following pregnancy.

  • 99. Toriola, Adetunji T
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schock, Helena
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Pukkala, Eero
    Chen, Tianhui
    Zeleniuch-Jacquotte, Anne
    Toniolo, Paolo
    Lehtinen, Matti
    Surcel, Helja-Marja
    Lukanova, Annekatrin
    Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 8, p. 1798-1801Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-I have been associated with increased risk of developing breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. This study was conducted to further characterize the association of IGF-I during pregnancy with maternal breast cancer risk.

    METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women younger than 40 years, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched with each case on age and date at blood donation. Serum IGF-I concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate ORs and 95% CIs.

    RESULTS: No significant associations were observed between serum IGF-I concentrations and breast cancer risk in both the overall analysis (OR, 1.08; 95% CI, 0.80-1.47) and in analyses stratified by histologic subtype, lag time to cancer diagnosis, age at pregnancy, or age at diagnosis.

    CONCLUSION: There was no association between IGF-I and maternal breast cancer risk during early pregnancy in this large nested case-control study.

    IMPACT: Serum IGF-I concentrations during early pregnancy may not be related to maternal risk of developing breast cancer.

  • 100. Toriola, Adetunji T
    et al.
    Surcel, Helja-Marja
    Husing, Anika
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Schock, Helena
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lehtinen, Matti
    Lukanova, Annekatrin
    Association of serum 25-hydroxyvitamin D (25-OHD) concentrations with maternal sex steroids and IGF-1 hormones during pregnancy2011In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 22, no 6, p. 925-928Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Vitamin D may influence circulating levels of sex steroid hormones in women during reproductive life, but associations in pregnant women have not been explored.

    METHODS: Correlation and linear regression models were used to assess the association between sex steroids, (estradiol, progesterone, 17-hydroxyprogesterone, testosterone, and androstenedione), IGF-1, and serum 25-hydroxyvitamin D (25-OHD) concentrations during the first trimester of pregnancy in 106 cancer-free women from the Finnish Maternity Cohort.

    RESULTS: There was no significant association of serum 25-OHD with any of the hormones measured. One-unit increase in serum 25-OHD concentration was associated with a non-significant 6% increase in estradiol concentrations. Multiparous women had higher levels of vitamin D (40.4 vs. 32.9 nmol/L, p-value = 0.01) than primiparous women.

    CONCLUSION: Our study does not support an association between maternal serum 25-OHD levels and sex steroids or IGF-I concentrations during the first trimester of pregnancy.

123 51 - 100 of 112
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf