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  • 101. Toriola, Adetunji T.
    et al.
    Surcel, Helja-Marja
    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
    Toniolo, Paolo
    Lehtinen, Matti
    Zeleniuch-Jacquotte, Anne
    Lukanova, Annekatrin
    Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case-control study2011In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 22, no 11, p. 1607-1611Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor-I (IGF-I) and C-reactive protein (CRP) may be positively associated with the risk of epithelial ovarian cancer (EOC) but no previous studies have investigated their associations with non-epithelial ovarian cancers (NEOC). A case-control study was nested within the Finnish Maternity Cohort. Case subjects were 58 women diagnosed with sex cord-stromal tumors (SCST) and 30 with germ cell tumors (GCT) after recruitment. Control subjects (144 for SCST and 74 for GCT) were matched for age, parity, and date of blood donation of the index case. Doubling of IGF-I concentration was not related to maternal risk of either SCST (OR 0.97, 95% CI 0.58-1.62) or GCT (OR 1.13, 95% CI 0.51-2.51). Similarly, doubling of CRP concentrations was not related to maternal risk of either SCST (OR 1.10, 95% CI 0.85-1.43) or GCT (OR 0.93, 95% CI 0.68-1.28). Pre-diagnostic IGF-I and CRP concentrations during the first trimester of pregnancy were not associated with increased risk of NEOC in the mother. Risk factors for NEOC may differ from those of EOC.

  • 102. Toriola, Adetunji T.
    et al.
    Tolockiene, Egle
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schock, Helena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Surcel, Helja-Marja
    Zeleniuch-Jacquotte, Anne
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Toniolo, Paolo
    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.
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Free beta- human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer2014In: Future Oncology, ISSN 1479-6694, E-ISSN 1744-8301, Vol. 10, no 3, p. 377-384Article in journal (Refereed)
    Abstract [en]

    Background: We investigated whether the free -human chorionic gonadotropin (free -hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Materials & methods: Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. Results: The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free -hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. Conclusion: In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free -hCG does not appear to provide any additional information.

  • 103. Toriola, Adetunji T
    et al.
    Vääräsmäki, Marja
    Lehtinen, Matti
    Zeleniuch-Jacquotte, Anne
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rodgers, Kenneth-Gary
    Lakso, Hans-Ake
    Chen, Tianhui
    Schock, Helena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Goran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Pukkala, Eero
    Toniolo, Paolo
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Surcel, Helja-Marja
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Determinants of maternal sex steroids during the first half of pregnancy2011In: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 118, no 5, p. 1029-1036Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:: To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone, and estradiol (E2).

    METHODS:: We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression.

    RESULTS:: Women older than age 30 years had lower androgen and E2 but higher progesterone concentrations than women younger than that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower E2 concentrations compared with nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared with nonsmoking women (all P<.05). E2 concentrations were 9% higher (P<.05) among women with a female fetus compared with those with a male fetus.

    CONCLUSION:: Parity, smoking, and, to a lesser extent, maternal age and child sex are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation.

    LEVEL OF EVIDENCE:: II.

  • 104. Trudel-Fitzgerald, Claudia
    et al.
    Poole, Elizabeth M.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sood, Anil K.
    Kawachi, Ichiro
    Kubzansky, Laura D.
    Tworoger, Shelley S.
    The Association of Work Characteristics With Ovarian Cancer Risk and Mortality2017In: Psychosomatic Medicine, ISSN 0033-3174, E-ISSN 1534-7796, Vol. 79, no 9, p. 1059-1067Article in journal (Refereed)
    Abstract [en]

    Objective: Ovarian cancer (OvCA) is a leading cause of cancer death for women. Depression and social isolation have been associated with a higher OvCA risk and poorer survival, but other forms of chronic psychosocial stress, including work-related characteristics, remain understudied. Methods: Women from three prospective cohorts (Nurses' Health Study: n = 31,754; Nurses' Health Study II: n = 74,260; Northern Sweden Health and Disease Study: n(nested case-control study) = 196) completed a job questionnaire, assessing demand and control at work, social support provided by coworkers and supervisor, and job security. Multivariate Cox and conditional logistic regression models estimated hazard ratios (Nurses' Health Study/Nurses' Health Study II) and odd ratios (Northern Sweden Health and Disease Study) of OvCA risk and mortality among cases. Random coefficient models were used for meta-analyses. Results: There were 396 OvCA cases and 186 deaths during follow-up. Overall, job strain, strain chronicity, social support, and job security were not significantly associated with OvCA risk (e.g., pooled relative risk [RR](high demand/low control) = 1.06, confidence interval [CI] = 0.72-1.55) or mortality (e.g., pooled RRhigh demand/low control = 1.08, CI = 0.64-1.82). When considered individually, compared with low levels, only moderate levels of demand were associated with a reduced OvCA risk (pooled RR = 0.66, CI = 0.49-0.90). Social support provided by the coworker or the supervisor did not moderate the association of job strain with either OvCA risk or overall mortality. Conclusions: We did not observe clear associations between work characteristics and OvCA incidence or mortality, but further research with diverse populations is warranted.

  • 105. Wentzensen, Nicolas A.
    et al.
    Poole, Elizabeth
    Arslan, Alan A.
    Patel, Alpa V.
    Setiawan, V. Wendy
    Visvanathan, Kala
    Weiderpass, Elisabete
    White, Emily
    Adami, Hans-Olov
    Brinton, Louise A.
    Bernstein, Leslie
    Buring, Julie
    Butler, Lesley M.
    Chamosa, Saioa
    Clendenen, Tess V.
    Dossus, Laure
    Fortner, Renee
    Gapstur, Susan M.
    Gaudet, Mia M.
    Gram, Inger Torhild
    Hartge, Patricia
    Hoffman-Bolton, Judith
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Jones, Michael
    Kaaks, Rudolf
    Kirsh, Vivki
    Koh, Woon-Puay
    Lacey, James V.
    Lee, I-Min
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Merritt, Melissa
    Peters, Ulrike
    Poynter, Jenny
    Rinaldi, Sabina
    Robien, Kim
    Rohan, Thomas
    Sandler, Dale P.
    Schouten, Leo J.
    Sjöholm, Louise
    Sieri, Sabina
    Swerdlow, Anthony
    Tjønneland, Anne
    Trabert, Britton
    Wilkens, Lynne
    Wolk, Alicja
    Yang, Hannah P.
    Zeleniuch-Jacquotte, Anne
    Tworoger, Shelley S.
    Ovarian cancer risk factors by histologic subtypes: evidence for etiologic heterogeneity2015In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75Article in journal (Other academic)
  • 106. Wentzensen, Nicolas
    et al.
    Poole, Elizabeth M.
    Trabert, Britton
    White, Emily
    Arslan, Alan A.
    Patel, Alpa V.
    Setiawan, V. Wendy
    Visvanathan, Kala
    Weiderpass, Elisabete
    Adami, Hans-Olov
    Black, Amanda
    Bernstein, Leslie
    Brinton, Louise A.
    Buring, Julie
    Butler, Lesley M.
    Chamosa, Saioa
    Clendenen, Tess V.
    Dossus, Laure
    Fortner, Renee
    Gapstur, Susan M.
    Gaudet, Mia M.
    Gram, Inger T.
    Hartge, Patricia
    Hoffman-Bolton, Judith
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Jones, Michael
    Kaaks, Rudolf
    Kirsh, Victoria
    Koh, Woon-Puay
    Lacey, James V., Jr.
    Lee, I-Min
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Merritt, Melissa A.
    Onland-Moret, N. Charlotte
    Peters, Ulrike
    Poynter, Jenny N.
    Rinaldi, Sabina
    Robien, Kim
    Rohan, Thomas
    Sandler, Dale P.
    Schairer, Catherine
    Schouten, Leo J.
    Sjoholm, Louise K.
    Sieri, Sabina
    Swerdlow, Anthony
    Tjonneland, Anna
    Travis, Ruth
    Trichopoulou, Antonia
    van den Brandt, Piet A.
    Wilkens, Lynne
    Wolk, Alicja
    Yang, Hannah P.
    Zeleniuch-Jacquotte, Anne
    Tworoger, Shelley S.
    Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 24, p. 2888-2898Article in journal (Refereed)
    Abstract [en]

    Purpose: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).

    Patients and Methods: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.

    Results: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.

    Conclusion: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.

  • 107. Witthöft, Cornelia M
    et al.
    Arkbåge, Karin
    Johansson, Madelene
    Lundin, Eva
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology. Patologi.
    Berglund, Gerd
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research. Näringsforskning.
    Zhang, Jie-Xian
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Lennernäs, Hans
    Dainty, Jack R
    Folate absorption from folate-fortified and processed foods using a human ileostomy model.2006In: British Journal of Nutrition, ISSN 0007-1145, Vol. 95, no 1, p. 181-7Article in journal (Refereed)
  • 108. Yang, Meng
    et al.
    Prescott, Jennifer
    Poole, Elizabeth M.
    Rice, Megan S.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    De Vivo, Immaculata
    Tworoger, Shelley S.
    Prediagnosis leukocyte telomere length and risk of ovarian cancer2016In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, article id B40Article in journal (Other academic)
    Abstract [en]

    Introduction: Ovarian cancer is characterized by substantial genomic instability. Telomeres, which protect the physical integrity of chromosomes, are shortened by each cell division, and evidence supports that longer telomeres may reduce genomic instability. While retrospective studies generally support an inverse association of telomere length and ovarian cancer risk, the measures of telomere length after diagnosis may be influenced by treatment. Therefore, we examined the relationship between leukocyte telomere length (LTL) assessed prior to diagnosis and risk of ovarian cancer in three prospective studies. Methods: We used buffy coat samples collected from healthy participants in the Nurses' Health Study (NHS), NHSII, and the Northern Sweden Health and Disease Study (NSHDS). Women who later developed ovarian cancer were matched to one or two controls on age, menopausal status, and date of blood collection. LTL was assessed using quantitative PCR-based assays in 5 batches with coefficients of variation of 10-15%. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression, based on study-specific quartiles in controls, for each study separately. We used fixed-effects models for meta-analysis. Multivariate models adjusted for oral contraceptive use, tubal ligation, family history of ovarian cancer, parity, smoking status, and body mass index. Results: In total, there were 487 cases and 810 controls across the three studies. The mean age at blood collection ranged from 45 (NHSII) to 57 (NHS) years. In unadjusted and multivariate models, we observed a suggestion of an inverse association between LTL and ovarian cancer risk in each study, although none of the trend tests were statistically significant. In a meta-analysis of the multivariate adjusted models, women in the longest versus shortest quartile of LTL had a non-significant 26% lower risk of ovarian cancer (OR=0.74; 95%CI=0.49-1.12; p-trend=0.33). Conclusion: In this first prospective study of telomere length and ovarian cancer risk, we observed that longer leukocyte telomere length was suggestively associated with lower ovarian cancer risk. Given that serous tumors are more likely to exhibit genomic instability, we are currently evaluating the association for this subtype as well as conducting pooled analyses with common quartile cut points across studies.

  • 109. Yang, Meng
    et al.
    Prescott, Jennifer
    Poole, Elizabeth M.
    Rice, Megan S.
    Kubzansky, Laura D.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    De Vivo, Immaculata
    Tworoger, Shelley S.
    Prediagnosis Leukocyte Telomere Length and Risk of Ovarian Cancer2017In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 3, p. 339-345Article in journal (Refereed)
    Abstract [en]

    Background: The associations between telomere length and cancer risk are equivocal, and none have examined the association between prediagnosis leukocyte telomere length (LTL) and the risk of developing ovarian cancer. Methods: We prospectively measured LTL collected from 442 ovarian cancer cases and 727 controls in the Nurses' Health Studies and the Northern Sweden Health and Disease Study. Cases were matched to one or two controls on age, menopausal status, and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: LTL was measured a median of 9.5 years before ovarian cancer diagnosis among cases. We observed a decreased risk of ovarian cancer with longer LTL. In multivariable models, women in the top quartile of LTL had an OR for ovarian cancer of 0.67 (95% CI, 0.46-0.97) compared with those in the bottom quartile. Inverse associations were stronger for nonserous cases (ORquartile (4 vs. quartile 1 of LTL) = 0.55, 95% CI, 0.33-0.94) and rapidly fatal cases (i.e., cases who died within 3 years of diagnosis; ORquartile 4 vs. quartile 1 of LTL = 0.55, 95% CI, 0.32-0.95). Conclusions: Our prospective findings suggest that longer circulating LTL may be associated with a lower ovarian cancer risk, especially for nonserous and rapidly fatal cases. The evaluation of LTL in relation to ovarian cancer risk by tumor subtypes is warranted in larger prospective studies. Impact: Prediagnosis LTL may reflect an early event in the ovarian cancer development and could serve as a biomarker to predict future risk.

  • 110. Zeleniuch-Jacquotte, A
    et al.
    Shore, R E
    Afanasyeva, Y
    Lukanova, A
    Sieri, S
    Koenig, K L
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Krogh, V
    Liu, M
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Muti, P
    Arslan, A A
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Berrino, F
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, P
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer2011In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, no 9, p. 1458-1464Article in journal (Refereed)
    Abstract [en]

    Background: It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.

    Methods: We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.

    Results: Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.

    Conclusion: Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

  • 111. Zeleniuch-Jacquotte, Anne
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Micheli, Andrea
    Koenig, Karen L
    Lenner, Per
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Muti, Paola
    Shore, Roy E
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Krogh, Vittorio
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Afanasyeva, Yelena
    Rinaldi, Sabina
    Arslan, Alan A
    Kaaks, Rudolf
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Adlercreutz, Herman
    Circulating enterolactone and risk of endometrial cancer2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 119, no 10, p. 2376-2381Article in journal (Refereed)
    Abstract [en]

    It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.

  • 112.
    Zheng, Wenjing
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gorre, Nagaraju
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Shen, Yue
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Noda, Tetsuo
    Ogawa, Wataru
    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.
    Maternal phosphatidylinositol 3-kinase signalling is crucial for embryonic genome activation and preimplantation embryogenesis2010In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 11, no 11, p. 890-895Article in journal (Refereed)
    Abstract [en]

    Maternal effect factors derived from oocytes are important for sustaining early embryonic development before the major wave of embryonic genome activation (EGA). In this study, we report a two-cell-stage arrest of embryos lacking maternal 3-phosphoinositide-dependent protein kinase 1 as a result of suppressed EGA. Concurrent deletion of maternal Pten completely rescued the suppressed EGA and embryonic progression through restored AKT signalling, which fully restored the fertility of double-mutant females. Our study identifies maternal phosphatidylinositol 3-kinase signalling as a new maternal effect factor that regulates EGA and preimplantation embryogenesis in mice.

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