umu.sePublications
Change search
Refine search result
1 - 37 of 37
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)
  • 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)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1. Belitskaya-Lévy, Ilana
    et al.
    Zeleniuch-Jacquotte, Anne
    Russo, Jose
    Russo, Irma H
    Bordás, Pal
    Ahman, Janet
    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.
    Li, Xiaochun
    de Cicco, Ricardo López
    Peri, Suraj
    Ross, Eric
    Russo, Patricia A
    Santucci-Pereira, Julia
    Sheriff, Fathima S
    Slifker, Michael
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Arslan, Alan A
    Characterization of a genomic signature of pregnancy identified in the breast2011In: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 4, no 9, 1457-1464 p.Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.

  • 2. Brendle, Annika
    et al.
    Brandt, Andreas
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist, Kerstin
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer: a Swedish prospective case-control study.2009In: European journal of cancer (Oxford, England : 1990), ISSN 1879-0852, Vol. 45, no 3, 435-442 p.Article in journal (Refereed)
    Abstract [en]

    Chromosomal instability (CIN) is a major characteristic of many cancers. We investigated whether putatively functional single nucleotide polymorphisms (SNPs) in genes related to CIN (CENPF, ESPL1, NEK2, PTTG1, ZWILCH, ZWINT) affect breast cancer (BC) risk and clinical outcome in a Swedish cohort of 749 incident BC cases with detailed clinical data and up to 15 years of follow-up and 1493 matched controls. As a main observation, carriers of the A allele of the CENPF SNP rs438034 had a worse BC-specific survival compared to the wild type genotype GG carriers (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.19-5.90), although they were less likely to have regional lymph node metastases (odds ratio (OR) 0.71, 95% CI 0.51-1.01) and tumours of stage II-IV (OR 0.73, 95% CI 0.54-0.99). As there is increasing evidence that CENPF is associated with poor prognosis in patients with primary BC, further independent studies are needed to clarify the importance of genetic variation in the CENPF gene in the clinic.

  • 3. Brendle, Annika
    et al.
    Lei, Haixin
    Brandt, Andreas
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist, Kerstin
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer ITGB4 as prognostic marker.2008In: Carcinogenesis, ISSN 1460-2180, Vol. 29, no 7, 1394-1399 p.Article in journal (Refereed)
    Abstract [en]

    Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19-3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21-3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.

  • 4. Chen, Tianhui
    et al.
    Lukanova, Annekatrin
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Zeleniuch-Jacquotte, Anne
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    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.
    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.
    IGF-I during primiparous pregnancy and maternal risk of breast cancer2010In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 121, no 1, 169-175 p.Article in journal (Refereed)
    Abstract [en]

    Previously, we reported that insulin-like growth factor (IGF)-I during early pregnancy is positively associated with maternal risk of breast cancer. To further explore this association, we designed a new study limited to women who donated a blood sample during their first pregnancy ending with childbirth. A case-control study was nested within the Northern Sweden Maternity Cohort in which repository since 1975, serum specimens remaining after early pregnancy screening for infectious diseases had been preserved. Study subjects were selected among women who donated a blood sample during the full-term pregnancy that led to the birth of their first child. Two hundred and forty-four women with invasive breast cancer were eligible. Two controls, matching the index case for age and date at blood donation were selected (n = 453). IGF-I was measured in serum samples on an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. A significant positive association of breast cancer with IGF-I was observed, with OR of 1.73 (95% CI: 1.14-2.63) for the top tertile, P < 0.009. Subgroup analyses did not indicate statistical heterogeneity of the association by ages at sampling and diagnosis or by lag time to cancer diagnosis, although somewhat stronger associations with risk were observed in women < or = age 25 at index pregnancy and for cases diagnosed within 15 years of blood donation. The results of the study add further evidence for an adverse effect of elevated IGF-I concentrations during early reproductive life on risk of breast cancer.

  • 5. Chen, Tianhui
    et al.
    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.
    Zeleniuch-Jacquotte, Anne
    Wulff, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Afanasyeva, Yelena
    Schock, Helena
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    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.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Toniolo, Paolo
    Lukanova, Annekatrin
    Maternal hormones during early pregnancy: a cross-sectional study2010In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 21, no 5, 719-727 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about correlates of first-trimester pregnancy hormones as in most studies maternal hormones have been measured later in gestation. We examined the associations of maternal characteristics and child sex with first-trimester maternal concentrations of four hormones implicated in breast cancer: human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), insulin-like growth factor (IGF)-I, and IGF-II. METHODS: About 338 serum samples donated to the Northern Sweden Maternity Cohort (NSMC), 1975-2001, during the first trimester of uncomplicated pregnancies, were analyzed for the hormones of interest as a part of a case-control study. The associations of maternal characteristics and child sex with hormone concentrations were investigated by correlation, general linear regression, and multivariate regression models. RESULTS: In the first trimester, greater maternal age was inversely correlated with IGF-I and IGF-II. In comparison with women carrying their first child, already parous women had higher IGF-I but lower hCG. Greater maternal weight and smoking were inversely correlated with hCG. No differences in hormone levels by child sex were observed. CONCLUSIONS: Our analyses indicated that potentially modifiable maternal characteristics (maternal weight and smoking) influence first-trimester pregnancy maternal hormone concentrations.

  • 6.
    Duchek, Milos
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jahnson, Staffan
    Mestad, Oddvar
    Hellström, Pekka
    Hellsten, Sverker
    Malmström, Per-Uno
    Bacillus Calmette-Guérin is superior to a combination of epirubicin and interferon-alpha2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study.2010In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, no 1, 25-31 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bacillus Calmette-Guérin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed.

    OBJECTIVE: To compare BCG to the combination of epirubicin and interferon-alpha2b as adjuvant therapy of T1 tumours.

    DESIGN, SETTING, AND PARTICIPANTS: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr.

    MEASUREMENTS: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented.

    RESULTS AND LIMITATIONS: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p=0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p=0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination.

    CONCLUSIONS: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

  • 7.
    Folkesson, Joakim
    et al.
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Påhlman, Lars
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Gunnarsson, Ulf
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Population-based study of local surgery for rectal cancer2007In: The British journal of surgery, ISSN 1365-2168, Vol. 94, no 11, 1421-1426 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim was to determine long-term survival and recurrence rates after local excision of rectal cancer from a prospectively registered population-based database. METHODS: Swedish Rectal Cancer Registry data from 1995 to 2001, including 10 181 patients of whom 643 (6.3 per cent) had a local excision, were analysed. Complete 5-year follow-up data from 1995 to 1998 were available. Cumulative relative and cancer-specific survival rates, and rates of local recurrence and distant metastases, were calculated by actuarial methods. RESULTS: The 5-year cancer-specific survival rate for 256 patients with stage I disease who had local excision was 95.3 (95 per cent confidence interval 91.5 to 99.1) per cent. The 5-year local recurrence rate was 7.2 per cent. After adjustment for age, sex, tumour stage and preoperative radiotherapy, the relative risk of death from cancer was the same as that after major resection. CONCLUSION: Population-based results after local excision of rectal cancer are the same as those reported in controlled series for early-stage tumours after abdominal resection. A low relative survival and a high median age indicate the use of local excision in patients with a high level of co-morbidity. To achieve acceptable long-term results, optimal preoperative and postoperative staging is needed.

  • 8. Gontero, Paolo
    et al.
    Sylvester, Richard
    Pisano, Francesca
    Joniau, Steven
    Eeckt, Kathy Vander
    Serretta, Vincenzo
    Larre, Stephane
    Di Stasi, Savino
    Van Rhijn, Bas
    Witjes, Alfred J.
    Grotenhuis, Anne J.
    Kiemeney, Lambertus A.
    Colombo, Renzo
    Briganti, Alberto
    Babjuk, Marek
    Malmström, Per-Uno
    Oderda, Marco
    Irani, Jacques
    Malats, Nuria
    Baniel, Jack
    Mano, Roy
    Cai, Tommaso
    Cha, Eugene K.
    Ardelt, Peter
    Varkarakis, John
    Bartoletti, Riccardo
    Spahn, Martin
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Frea, Bruno
    Soukup, Viktor
    Xylinas, Evanguelos
    Dalbagni, Guido
    Karnes, R. Jeffrey
    Shariat, Shahrokh F.
    Palou, Joan
    Prognostic Factors and Risk Groups in T1G3 Non-Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guerin: Results of a Retrospective Multicenter Study of 2451 Patients2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, no 1, 74-82 p.Article in journal (Refereed)
    Abstract [en]

    Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

  • 9. Göhler, Stella
    et al.
    Da Silva Filho, Miguel Inacio
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist-Olsson, Kerstin
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Cancer Center Stockholm Gotland, Stockholm, Sweden .
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population2016In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 142, no 1, 273-276 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: The C -> T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a similar to 29. 5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk. Methods: We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC. Results: No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model). Conclusion: The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.

  • 10. Hassler, Sven
    et al.
    Sjölander, Per
    Grönberg, Henrik
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cancer in the Sami population of Sweden in relation to lifestyle and genetic factors.2008In: Eur J Epidemiol, ISSN 0393-2990, Vol. 23, no 4, 273-280 p.Article in journal (Refereed)
    Abstract [en]

    The reindeer herding Sami of Sweden have low incidences of cancer. The aim of the present study was to investigate the cancer risk in a large cohort of Swedish Sami, containing Sami with different lifestyle and genetic Sami heritage. A cohort of 41,721 Sami identified in official national registers between 1960 and 1997, was divided into two sub-populations -- reindeer herding Sami (RS) and non-reindeer herding Sami (NRS). A demographically matched non-Sami reference population (NS) was used as standard when incidence and mortality ratios were calculated. Incidence and mortality data were obtained from the Swedish Cancer and Cause of Death Registers for the period 1961-2003. For Sami men, lower risks were found for cancers of the colon and prostate, and for malignant melanoma and non-Hodkins lymphoma, but higher for stomach cancer. The Sami women showed higher risks for cancers of the stomach and the ovaries, but lower risk for cancer of the bladder. The RS demonstrated lower relative cancer risks compared with the NRS. The lowest relative risk was found among the RS men, while the highest were observed among the NRS women. The RS men who had adopted a more westernized lifestyle showed a similar relative risk for prostate cancer as that of the NS living in the same region. Most of these differences in cancer risks could probably be ascribed to differences in lifestyle. It is concluded that the traditional Sami lifestyle contains elements, e.g. dietary contents and physical activity that may protect them from developing cancer.

  • 11. Hedlund, Per Olov
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Jan Erik
    Hagerman, Inger
    Henriksson, Peter
    Iversen, Peter
    Klarskov, Peter
    Mogensen, Peter
    Rasmussen, Finn
    Varenhorst, Eberhard
    Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer: Evaluation of cardiovascular events in a randomized trial2011In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 45, no 5, 346-353 p.Article in journal (Refereed)
    Abstract [en]

    Objective. This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin (R)) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease. Material and methods. Nine-hundred and fifteen patients with T0-4, Nx, M1, G1-3, hormone- naive prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin (R)) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl (R)) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression. Results. There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p < 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036). Conclusions. Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e. g. avoidance of osteopenia and hot flushes and the low price, are given priority.

  • 12. Hemdan, Tammer
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jahnson, Staffan
    Hellstrom, Pekka
    Tasdemir, Ilker
    Malmstrom, Per-Uno
    Five-year results of nordic T1G2-3, a randomized trial comparing bcg with epirubicin and interferon alpha 2b2013In: Scandinavian journal of urology, ISSN 2168-1805, Vol. 47, no Suppl. 219, 19-20 p.Article in journal (Other academic)
  • 13. Jorgren, F.
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindmark, G.
    Anastomotic leakage after surgery for rectal cancer: a risk factor for local recurrence, distant metastasis and reduced cancer-specific survival?2011In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 13, no 3, 272-283 p.Article in journal (Refereed)
    Abstract [en]

    Aim The impact of anastomic leakage (AL) on the oncological outcome after anterior resection (AR) for rectal cancer is still controversial. We explored the impact of AL regarding local recurrence (LR), distant metastasis and overall recurrence (OAR). Overall and cancer-specific survival was analysed. Method Patients undergoing AR for rectal cancer with a registered AL between 1995 and 1997 and a control group were identified in the Swedish Rectal Cancer Registry. The medical records were retrieved for additional data and validation. Differences in the oncological outcome at 5-year follow-up were analysed with multivariate methods. Results After validation, 114 patients with AL and 136 control patients with locally radical surgery for tumours in tumour-node-metastasis stages I-III were analysed. There was no difference detected between patients with AL and control patients regarding rates of LR [8% (9 of 114) vs 9% (12 of 136); P = 0.97], distant metastasis [18% (20 of 114) vs 23% (31 of 136); P = 0.37] and OAR [19% (22 of 114) vs 28% (38 of 136); P = 0.15]. The 5-year cancer-specific survival was almost 80% in both groups. In multivariate analysis, AL was not a risk factor of LR, distant metastasis or OAR and had no impact on 5-year overall or 5-year cancer-specific survival. Irrespective of the occurrence of AL, preoperative radiotherapy (P = 0.055) and rectal washout (P = 0.046) reduced the LR rate, but did not influence survival. Conclusion Anastomotic leakage was not proved to be a risk factor of worse oncological outcome. Hence, additional adjuvant treatment or extended follow-up on the basis of the occurrence of AL after AR might not be justified.

  • 14. Jörgren, Fredrik
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindmark, Gudrun
    Oncological outcome after incidental perforation in radical rectal cancer surgery2010In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 25, no 6, 731-740 p.Article in journal (Refereed)
    Abstract [en]

    Identification of risk factors of poor oncological outcome in rectal cancer surgery is of utmost importance. This study examines the impact of incidental perforation on the oncological outcome. Using the Swedish Rectal Cancer Registry, patients were selected who received major abdominal surgery for rectal cancer between 1995 and 1997 with registered incidental perforation. A control group was also selected for analysis of the oncological outcome after 5-year follow-up. Multivariate analysis was performed. Registry data were validated, and additional data were supplemented from medical records. After validation and exclusion of non-radically operated patients, 118 patients with incidental perforation and 155 controls in TNM stages I-III were included in the analysis. The rate of local recurrence (LR) [20% (23/118) vs. 8% (12/155) (p = 0.007)] was significantly higher among patients with perforation, whereas the rates of distant metastasis [27% (32/118) vs. 21% (33/155) (p = 0.33)] and overall recurrence (OAR) [35% (41/118) vs. 25% (38/155) (p = 0.087)] were not significantly different between the groups. Overall as well as cancer-specific 5-year survival rates were significantly reduced for the patients with perforation [44 vs. 64% (p = 0.002) and 66 vs. 80% (p = 0.026), respectively]. In the multivariate analysis, perforation was a significant risk factor of increased rates of LR and OAR as well as reduced 5-year overall and cancer-specific survival. Incidental perforation in rectal cancer surgery is an important risk factor of poor oncological outcome and should be considered in the discussion concerning postoperative adjuvant treatment as well as the follow-up regime.

  • 15. Jörgren, Fredrik
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindmark, Gudrun
    Risk factors of rectal cancer local recurrence: population-based survey and validation of the Swedish rectal cancer registry2010In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 12, no 10, 977-986 p.Article in journal (Refereed)
    Abstract [en]

    Aim: Despite advances in rectal cancer treatment, local recurrence (LR) remains a significant problem. To select high-risk patients for different treatment options aimed at reducing LR, it is essential to identify LR risk factors. Method: Local recurrence and survival rates of 4153 patients registered 1995-1997 in the Swedish Rectal Cancer Registry were analysed. LR risk factors were analysed by multivariate methods. For LR patients the registry was validated and additional data retrieved. Results: The 5-year overall and cancer-specific survival rates were 45% and 62% respectively. LR was registered in 326 (8%) patients. After R0-resections for tumours in TNM stages I-III, LR developed in 10% of tumours at 0-5 cm, 8% at 6-10 cm and 6% at 11-15 cm above the anal verge. Preoperative radiotherapy (RT) reduced the LR rate irrespective of height [0-5 cm: OR 0.50 (0.30-0.83), 6-10 cm: OR 0.42 (0.25-0.71), and 11-15 cm: OR 0.29 (0.13-0.64)]. Patients without preoperative RT had significantly higher LR risk after rectal perforation [OR 2.50 (1.48-4.24)], and almost significantly decreased LR risk when rectal washout was performed [OR 0.65 (0.43-1.00)]. Preoperative RT prolonged time to LR but did not significantly influence the survival among LR patients. LR was an isolated tumour manifestation in 103 (39%) patients with validated LR. Conclusion: Preoperative RT should be considered for rectal cancer also in the upper third of the rectum. Intraoperative perforation should be avoided, and rectal washout is indicated as valuable. Follow-up for the detection of isolated LR is important. Extended follow up should be considered for patients treated with RT.

  • 16. Jörgren, Fredrik
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre North, Umeå University.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre North, Umeå University.
    Lindmark, Gudrun
    Validity of the Swedish Rectal Cancer Registry for patients treated with major abdominal surgery between 1995 and 19972013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 8, 1707-1714 p.Article in journal (Refereed)
    Abstract [en]

    Background. Founded in 1995, the Swedish Rectal Cancer Registry (SRCR) is frequently used for rectal cancer research. However, the validity of the registry has not been extensively studied. This study aims to validate a large amount of registry data to assess SRCR quality.

    Material and methods. The study comprises 906 patients treated with major abdominal surgery registered in the SRCR between 1995 and 1997. SRCR data for 14 variables were scrutinized for validity against the medical records. Kappa's and Kendall's correlation coefficients for agreement between SRCR data and medical records data were calculated for 13 variables.

    Results. For 11 variables, concerning the tumor, neoadjuvant therapy, the surgical procedure, local radicality and TNM stage, data were missing in 5% or less of the registrations; for the remaining three variables, anastomotic leakage, local and distant recurrence, data were missing in 13-38%. For the variables surgery performed or not and type of surgical procedure, no data were missing. Erroneous registrations were found in less than 10% of all variables; for the variables preoperative chemotherapy and surgery performed or not, all registrations were correct. For the variables concerning neoadjuvant therapy, local radicality according to the surgeon as well as the pathologist and distant metastasis, the false-positive or- negative registrations were equally distributed, and for the variables rectal washout, rectal perforation, anastomotic leakage and local recurrence there was a discrepancy in distribution. The correlation coefficient for 12 variables ranged from 0.82 to 1.00, and was 0.78 for the remaining variable.

    Conclusion. The validity of the SRCR was good for the initial three registry years. Thus, research based on SRCR data is reliable from the beginning of the registry's use.

  • 17. Kodeda, K.
    et al.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zar, N.
    Birgisson, H.
    Dahlberg, M.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Skullman, S.
    Lindmark, G.
    Glimelius, B.
    Pahlman, L.
    Martling, A.
    Time trends, improvements and national auditing of rectal cancer management over an 18-year period2015In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 17, no 9, O168-O179 p.Article in journal (Refereed)
    Abstract [en]

    AimThe main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. MethodData from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. ResultsDuring the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. ConclusionThere have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

  • 18. Lei, Haixin
    et al.
    Hemminki, Kari
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Altieri, Andrea
    Enquist, Kerstin
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    PAI-1 -675 4G/5G polymorphism as a prognostic biomarker in breast cancer.2008In: Breast Cancer Res Treat, ISSN 0167-6806, Vol. 109, no 1, 165-175 p.Article in journal (Refereed)
    Abstract [en]

    Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor prognosis in breast cancer. We examined whether genetic variation in the genes of the uPA system affect breast cancer susceptibility and prognosis. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in six genes of the uPA system in 959 Swedish breast cancer patients with detailed clinical data and up to 15 years of follow-up together with 952 matched controls. We used the unconditional logistic regression models to evaluate the associations between genotypes and breast cancer risk and tumor characteristics. The Kaplan-Meier method was used to estimate the survival probabilities; the log-rank test was used to test differences between subgroups. None of the SNPs conferred an increased breast cancer risk, but correlation with some traditional prognostic factors was observed for several SNPs. Most importantly, we identified the -675 4G/5G SNP in the PAI-1 gene as a promising prognostic biomarker for breast cancer. Compared to the 4G/4G and 4G/5G genotypes 5G/5G homozygosity correlated significantly with worse survival (RR 2.04, 95% CI 1.45-2.86, P<0.001), especially in patients with more aggressive tumors. 5G/5G homozygotes were also the group with worse survival among lymph node negative cases. Our finding suggests that genotyping PAI-1 -675 4G/5G may help in clinical prognosis of breast cancer.

  • 19. Lei, Haixin
    et al.
    Hemminki, Kari
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Altieri, Andrea
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Single nucleotide polymorphisms in the DMBT1 promoter and the progression of breast cancer2006In: Int J Cancer, ISSN 0020-7136, Vol. 120, no 2, 447-449 p.Article in journal (Refereed)
  • 20. 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, 1284-1291 p.Article 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.

  • 21. Martling, A
    et al.
    Granath, F
    Cedermark, B
    Johansson, Robert
    Holm, T
    Gender differences in the treatment of rectal cancer: a population based study2009In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 35, no 4, 427-433 p.Article in journal (Refereed)
    Abstract [en]

    Aims: Colorectal cancer is the second most common type of cancer in both women and men in Sweden. A National Quality Register for rectal adenocarcinoma in Sweden has included 97% of all rectal cancer patients since 1995. A previous study, based on data from the treatment program register in the Stockholm-Gotland region. found that women in Stockholm received preoperative radiotherapy (RT) less often than men [Martling A. Rectal cancer: staging, radiotherapy and surgery, ISBN: 91-7349-461-5. Stockholm: Karolinska Institute: 2003].(1) The aim of this study was to assess if women and men with rectal cancer receive equal treatment oil a national level, and whether any potential dissimilarity causes measurable consequences in Outcome. regarding postoperative morbidity and mortality, turnout, recurrence and Survival.

    Methods: All patients with rectal cancer included in the National Quality Register between 1995 and 2002 (11 774 patients) were analysed. Gender was correlated to treatment, postoperative morbidity and mortality, local recurrence and death.

    Results: The proportion of women selected for preoperative RT was significantly lower than that of men (42.5% vs. 50.1%, p < 0.001). After adjustment for other prognostic factors, the significant difference in the treatment strategy among women and men persisted. Postoperative mortality was significantly higher in men than in women and the gender difference was most pronounced in irradiated patients. RT improved local control significantly in both women and men but it had no effect oil cancer specific survival.

    Conclusions: For unknown reasons women less often received adjuvant RT than men. The opposite appeared to be a more adequate alternative. There is a need of improved selection criteria for RT in both men and women with rectal cancer.

  • 22.
    Norberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Intracranial tumours after external fractionated radiotherapy for pituitary adenomas in northern Sweden2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 8, 1276-1282 p.Article in journal (Refereed)
    Abstract [en]

    The results indicate an increased risk of second primary intracranial tumours in patients treated with radiotherapy for pituitary adenomas, compared to patients not exposed to irradiation and to the general population. Meningiomas were more frequent than gliomas and the median time interval between radiotherapy and second intracranial tumour was 17 years.

  • 23.
    Norberg, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Pituitary adenomas in northern Sweden. A study on therapy choices and the risk of second primary tumours.2008In: Clin Endocrinol (Oxf), ISSN 1365-2265, Vol. 68, no 5, 780-785 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    To present the incidence of pituitary adenomas in northern Sweden and to determine whether the incidence of second primary tumours differs from the incidence in the general population or might be related to radiotherapy.

    DESIGN:

    A retrospective register study.

    PATIENTS:

    A total of 546 patients with pituitary adenomas were identified in the Cancer Registry of northern Sweden between 1958 and 2004. Only patients with histopathological verification and/or endocrine activity of the adenoma and more than 12 months of follow-up were included, resulting in 376 patients in the study.

    MEASUREMENTS:

    The number of patients receiving surgery and/or radiotherapy and presenting second primary tumours were registered. Standard incidence ratios (SIRs) between the observed and the expected incidence of second primary tumours were calculated.

    RESULTS:

    The total number of person-years at risk for a second primary tumour was 4730. Fifty-four out of 376 (14%) patients had 63 second primary tumours. Forty patients had second primary tumours diagnosed more than 12 months after diagnosis of the pituitary adenoma (expected 42.6, SIR 0.94, 95% CI 0.67-1.28). A significantly increased incidence of second primary tumours was seen in 42 men with GH-secreting adenomas. Ten second tumours were found (expected 4.55, SIR 2.20, 95% CI 1.05-4.04). A total of 261 patients received radiotherapy and 31 second primary tumours occurred after radiotherapy (expected 32.9, SIR 0.94, 95% CI 0.64-1.34). Three second primary intracranial tumours appeared within the irradiation volume (expected 0.85, SIR 3.51, 95% CI 0.71-10.36).

    CONCLUSIONS:

    No significant increase was found in the incidence of second primary tumours in general in patients with pituitary adenomas. An increased incidence of second primary tumours was seen in men with GH-secreting adenomas.

  • 24. Peri, Suraj
    et al.
    de Cicco, Ricardo Lopez
    Santucci-Pereira, Julia
    Slifker, Michael
    Ross, Eric A
    Russo, Irma H
    Russo, Patricia A
    Arslan, Alan A
    Belitskaya-Levy, Ilana
    Zeleniuch-Jacquotte, Anne
    Bordas, Pal
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Åhman, Janet
    Afanasyeva, Yelena
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sheriff, Fathima
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Russo, Jose
    Defining the genomic signature of the parous breast2012In: BMC Medical Genomics, ISSN 1755-8794, E-ISSN 1755-8794, Vol. 5, 46- p.Article in journal (Refereed)
    Abstract [en]

    Background: It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy.

    Methods: In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry.

    Results: We identified 305 differentially expressed probesets (208 distinct genes). Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis.

    Conclusions: This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process.

  • 25. Shi, Hong
    et al.
    Bevier, Melanie
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist-Olsson, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Foersti, Asta
    Prognostic impact of polymorphisms in the MYBL2 interacting genes in breast cancer2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 131, no 3, 1039-1047 p.Article in journal (Refereed)
    Abstract [en]

    MYBL2 is a transcription factor, which regulates the expression of genes involved in cancer progression. In this study, we investigated whether putative functional variants in genes regulating MYBL2 (E2F1, E2F3 and E2F4) or in genes, which are regulated by MYBL2 (BCL2, BIRC5, COL1A1, COL1A2, COL5A2, ERBB2, CLU, LIN9 and TOP2A) affect breast cancer (BC) susceptibility and clinical outcome. Twenty-eight SNPs were genotyped in a population-based series of 782 Swedish BC cases and 1,559 matched controls. BC-specific survival analysis of BIRC5 suggested that carriers of the minor allele of rs8073069 and rs1042489 have a worse survival compared with the major homozygotes (HR 2.46, 95% CI 1.39-4.36 and HR 1.81, 95% CI 1.01-3.25, respectively). The poor survival was observed especially in women with aggressive tumours. Multivariate analysis supported the role of rs8073069 as an independent prognostic marker. For BCL2, minor allele carriers of rs1564483 were more likely to have hormone receptor-positive tumours than the major homozygotes. Another SNP in BCL2, rs4987852, was associated with tumour stages II-IV and histologic grade 3. In CLU, the minor allele carriers of rs9331888 were more likely to have tumours with regional lymph node metastasis and stages II-IV than the major homozygotes. In conclusion, our study suggests a role of genetic variation in BIRC5, BCL2 and CLU as progression and prognostic markers for BC, supporting previous studies based on the expression of the genes.

  • 26. Stacey, Simon N
    et al.
    Sulem, Patrick
    Zanon, Carlo
    Gudjonsson, Sigurjon A
    Thorleifsson, Gudmar
    Helgason, Agnar
    Jonasdottir, Aslaug
    Besenbacher, Soren
    Kostic, Jelena P
    Fackenthal, James D
    Huo, Dezheng
    Adebamowo, Clement
    Ogundiran, Temidayo
    Olson, Janet E
    Fredericksen, Zachary S
    Wang, Xianshu
    Look, Maxime P
    Sieuwerts, Anieta M
    Martens, John W M
    Pajares, Isabel
    Garcia-Prats, Maria D
    Ramon-Cajal, Jose M
    de Juan, Ana
    Panadero, Angeles
    Ortega, Eugenia
    Aben, Katja K H
    Vermeulen, Sita H
    Asadzadeh, Fatemeh
    van Engelenburg, K C Anton
    Margolin, Sara
    Shen, Chen-Yang
    Wu, Pei-Ei
    Försti, Asta
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jonsson, Thorvaldur
    Sigurdsson, Helgi
    Alexiusdottir, Kristin
    Gudmundsson, Julius
    Sigurdsson, Asgeir
    Frigge, Michael L
    Gudmundsson, Larus
    Kristjansson, Kristleifur
    Halldorsson, Bjarni V
    Styrkarsdottir, Unnur
    Gulcher, Jeffrey R
    Hemminki, Kari
    Lindblom, Annika
    Kiemeney, Lambertus A
    Mayordomo, Jose I
    Foekens, John A
    Couch, Fergus J
    Olopade, Olufunmilayo I
    Gudbjartsson, Daniel F
    Thorsteinsdottir, Unnur
    Rafnar, Thorunn
    Johannsson, Oskar T
    Stefansson, Kari
    Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.2010In: PLoS genetics, ISSN 1553-7404, Vol. 6, no 7, e1001029- p.Article in journal (Refereed)
    Abstract [en]

    We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.

  • 27.
    Stattin, Pär
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Vickers, Andrew J.
    New York, NY, USA.
    Sjoberg, Daniel D.
    New York, NY, USA.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Granfors, Torvald
    Stockholm, Sweden.
    Johansson, Mattias
    Section of Genetics, The International Agency for Research on Cancer, Lyon, France.
    Pettersson, Kim
    Turku, Finland.
    Scardino, Peter T.
    New York, NY, USA.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Lilja, Hans
    New York, NY, USA; Headington, Oxford, UK; Malmö, Sweden.
    Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: a Nested Case-Control Study2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, no 2, 207-213 p.Article in journal (Refereed)
    Abstract [en]

    Background: A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. Objective: To increase the specificity of screening for lethal PCa at an early stage. Design, setting, and participants: We conducted a case-control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Vasterbotten, Sweden. Of 40 379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12 542 men were followed for > 15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Outcome measurements and statistical analysis: Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Results and limitations: Mostmetastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (<= 0.6%). Among men with PSA > 2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA > 2 ng/ml were defined as low risk by this model and had a <= 1% 15-yr risk of metastasis. Conclusions: Screening at ages 50-60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. Patient summary: For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.

  • 28. Thomsen, Hauke
    et al.
    da Silva Filho, Miguel Inacio
    Woltmann, Andrea
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Eyfjord, Jorunn E.
    Hamann, Ute
    Manjer, Jonas
    Enquist-Olsson, Kerstin
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Cancer Center Stockholm Gotland, Stockholm, Sweden.
    Herms, Stefan
    Hoffmann, Per
    Chen, Bowang
    Huhn, Stefanie
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Foersti, Asta
    Inbreeding and homozygosity in breast cancer survival2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 16467Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.) The association of individual SNPs indicated no differences in the proportions of homozygous individuals among short-time survivors (STSs) and long-time survivors (LTSs). (II.) The analysis revealed differences among the populations for the number of ROHs per person and the total and average length of ROHs per person and among LTSs and STSs for the number of ROHs per person. (III.) Common ROHs at particular genomic positions were nominally more frequent among LTSs than in STSs. Common ROHs showed significant evidence for natural selection (iHS, Tajima's D, Fay-Wu's H). Most regions could be linked to genes related to BC progression or treatment. (IV.) Results were supported by a higher level of inbreeding among LTSs. Our results showed that an increased level of homozygosity may result in a preference of individuals during BC treatment. Although common ROHs were short, variants within ROHs might favor survival of BC and may function in a recessive manner.

  • 29. 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, 6779-6786 p.Article 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.

  • 30. Van den Broek, C. B. M.
    et al.
    van Gijn, W.
    Bastiaannet, E.
    Møller, B.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Elferink, M. A. G.
    Wibe, A.
    Påhlman, L.
    Iversen, L. H.
    Penninckx, F.
    Valentini, V.
    van de Velde, C. J. H.
    Differences in pre-operative treatment for rectal cancer between Norway, Sweden, Denmark, Belgium and the Netherlands2014In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, no 12, 1789-1796 p.Article in journal (Refereed)
    Abstract [en]

    Several studies have shown remarkable differences in colorectal cancer survival across Europe. Most of these studies lacked information about stage and treatment. In this study we compared short-term survival as well as differences in tumour stage and treatment strategies between five European countries: Norway, Sweden, Denmark, Belgium, and the Netherlands. For this retrospective cohort study all patients aged 18 years or older and operated on adenocarcinoma of the rectum without distant metastases and diagnosed in 2008 and 2009 were selected in national audit registries from Norway, Sweden, Denmark, Belgium, and the Netherlands. Differences in pre-operative treatment between the countries were compared using univariable and multivariable logistic regression. One year relative survival and one year relative excess risk of death (RER) were compared between the five countries. Large variation in the use of preoperative radiotherapy and chemoradiation was found between the countries. Even though, there was little variation in relative survival between the countries, except Sweden, which had a significant better one year RER of death among the elderly patients after adjustment. The differences in survival are expected to be caused by differences in pen-operative care, selection of patients, and especially management of elderly patients. The effects of preoperative treatment are expected to be seen on long term follow-up. 

  • 31. Varadi, Verena
    et al.
    Bevier, Melanie
    Grzybowska, Ewa
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Butkiewicz, Dorota
    Pamula-Pilat, Jolanta
    Tecza, Karolina
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Foersti, Asta
    Genetic variation in genes encoding for polymerase zeta subunits associates with breast cancer risk, tumour characteristics and survival2011In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 129, no 1, 235-245 p.Article in journal (Refereed)
    Abstract [en]

    Chromosomal instability is a known hallmark of many cancers. DNA polymerases represent a group of enzymes that are involved in the mechanism of chromosomal instability as they have a central function in DNA metabolism. We hypothesized that genetic variation in the polymerase genes may affect gene expression or protein configuration and by that cancer risk and clinical outcome. We selected four genes encoding for the catalytic subunits of the polymerases beta, delta, theta and zeta (POLB, POLD1, POLQ and REV3L, respectively) and two associated proteins (MAD2L2 and REV1) because of their previously reported association with chromosomal instability and/or tumorigenesis. We selected potentially functional and most informative tagging single nucleotide polymorphisms (SNPs) for genotyping in a population-based series of 783 Swedish breast cancer (BC) cases and 1562 controls. SNPs that showed a significant association in the Swedish population were additionally genotyped in a Polish population consisting of 506 familial/early onset BC cases and 568 controls. SNPs in all three polymerase zeta subunit genes associated either with BC risk or prognosis. Two SNPs in REV3L and one SNP in MAD2L2 associated with BC risk: rs462779 (multiplicative model: OR 0.79, 95% CI 0.68-0.92), rs3204953 (dominant model: OR 1.28, 95% CI 1.05-1.56) and rs2233004 (recessive model: OR 0.49, 95% CI 0.28-0.86). Homozygous carriers of the minor allele C of the third SNP in REV3L, rs11153292, had significantly worse survival compared to the TT genotype carriers (HR 2.93, 95% CI 1.34-6.44). Minor allele carriers of two REV1 SNPs (rs6761391 and rs3792142) had significantly more often large tumours and tumours with high histological grade and stage. No association was observed for SNPs in POLB, POLQ and POLD1. Altogether, our data suggest a significant role of genetic variation in the polymerase zeta subunit genes regarding the development and progression of BC.

  • 32. Varadi, Verena
    et al.
    Bevier, Melanie
    Grzybowska, Ewa
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist-Olsson, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Butkiewicz, Dorota
    Pamula-Pilat, Jolanta
    Tecza, Karolina
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Genetic variation in ALCAM and other chromosomal instability genes in breast cancer survival2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 131, no 1, 311-319 p.Article in journal (Refereed)
    Abstract [en]

    Chromosomal instability is a hallmark of many cancers and it has a potential to predict clinical outcome of a cancer patient. We hypothesized that genes whose expression status differs between chromosomal stable and unstable breast tumors represent target genes for the identification of genetic variants predicting breast cancer (BC) risk, disease progression, and survival. We used a published list of 38 genes associated with chromosomal instability as a basis for searching potentially functional and informative tagging single nucleotide polymorphisms (SNPs). As a result, 33 SNPs in 16 genes were genotyped in a population-based series of 783 Swedish BC cases. Two SNPs in the ALCAM gene associated with BC-specific survival. For rs1044243, the HR was 4.35 (95% CI 1.34-14.18), and for rs1157, the HR was 3.42 (95% CI 1.32-8.83) for the homozygous carriers of the minor alleles. For the minor allele carriers of CCL18 SNP rs14304, we observed a significant association with aggressive tumor characteristics: large tumor size (OR 1.53, 95% CI 1.10-2.14), positive lymph node metastasis (OR 1.75, 95% CI 1.02-3.00), and high stage (OR 1.37, 95% CI 1.02-1.85). In a Polish population consisting of 506 familial/early onset BC cases, no association with event-free survival for the ALCAM SNPs nor any association with tumor characteristics for the CCL18 SNP were observed, suggesting either a chance finding in the Swedish population or population-based or etiological differences between sporadic and familial/early onset BC.

  • 33. Varadi, Verena
    et al.
    Brendle, Annika
    Brandt, Andreas
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Svenson, Ulrika
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Polymorphisms in telomere-associated genes, breast cancer susceptibility and prognosis2009In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 45, no 17, 3008-3016 p.Article in journal (Refereed)
    Abstract [en]

    Telomeres are essential structures for maintaining chromosomal stability and their length has been reported to correlate with cancer risk and clinical outcome. Single nucleotide polymorphisms (SNPs) in genes encoding telomere-associated proteins could affect telomere length and chromosomal stability by influencing gene expression or protein configuration in the telomeres. Here, we report the results of the first association study on genetic variation in telomere-associated genes and their effect on telomere length, breast cancer (BC) susceptibility and prognosis. We genotyped 14 potentially functional and most informative SNPs in nine telomere-associated genes (TERT, TEP1, TERF1, TERF2, TERF2IP, ACD, POT1, TNKS and TNKS2) in 782 incident BC cases and 1559 matched controls. Relative telomere length (RTL) varied statistically significantly between the genotypes of the SNPs rs446977 (TEP1, p=0.04), rs938886 (TEP1, p=0.04) and rs6990097 (TNKS, p=0.04). However, none of them was associated with BC susceptibility and only rs6990097 correlated with regional lymph node metastasis (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.08-1.77). The strongest association with BC susceptibility was observed for rs3785074 (TERF2, OR 0.51, 95% CI 0.31-0.83) and rs10509637 (TNKS2, OR 1.33, 95% CI 1.08-1.62). Haplotype and diplotype analysis confirmed the association of the TNKS2 gene with BC susceptibility. rs3785074 (TERF2) was additionally associated with histologic grade (OR 1.44, 95% CI 1.08-1.92) and negative oestrogen receptor status (OR 2.93, 95% CI 1.13-7.58). None of the SNPs showed a significant correlation with survival of the breast cancer patients. With these results, none of the SNPs represents any valuable prognostic marker for BC.

  • 34.
    Varadi, Verena
    et al.
    Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld ,Heidelberg, Germany.
    Brendle, Annika
    Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.
    Grzybowska, Ewa
    Department of Molecular Biology, Center of Oncology, Maria Sklodowska-Curie Institute, Gliwice, Poland.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Butkiewicz, Dorota
    Department of Tumor Biology, Center of Oncology, Maria Sklodowska-Curie Institute, Gliwice, Poland.
    Pamula-Pilat, Jolanta
    Department of Molecular Biology, Center of Oncology, Maria Sklodowska-Curie Institute, Gliwice, Poland.
    Pekala, Wioletta
    Department of Molecular Biology, Center of Oncology, Maria Sklodowska-Curie Institute, Gliwice, Poland.
    Hemminki, Kari
    Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany.
    A functional promoter polymorphism in the TERT gene does not affect inherited susceptibility to breast cancer2009In: Cancer Genetics and Cytogenetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 190, no 2, 71-74 p.Article in journal (Refereed)
    Abstract [en]

    Telomere dysfunction is a key mechanism in cancer development. The human telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of the telomerase enzyme, which is necessary for the maintenance of telomere DNA length, chromosomal stability, and cellular immortality. In our attempt to identify functional polymorphisms in the TERT gene and their effect on breast cancer risk, we sequenced the promoter of the gene and identified three single nucleotide polymorphisms (SNPs) with a frequency of at least 10%. One of these SNPs, rs2853669 (-244 T > C), has been shown to affect telomerase activity and telomere length. Recently, this SNP has been suggested to affect familial breast cancer risk. In our case-control study using two large breast cancer sample series, including one with 841 cases with inherited susceptibility to breast cancer, we did not find any association with familial or sporadic breast cancer risk. This well-powered study excludes an effect of the functional -244 T > C SNP and two other correlated SNPs on breast cancer risk.

  • 35. Veiga, Lene H. S.
    et al.
    Holmberg, Erik
    Anderson, Harald
    Pottern, Linda
    Sadetzki, Siegal
    Adams, M. Jacob
    Sakata, Ritsu
    Schneider, Arthur B.
    Inskip, Peter
    Bhatti, Parveen
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Neta, Gila
    Shore, Roy
    de Vathaire, Florent
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kleinerman, Ruth
    Hawkins, Michael M.
    Tucker, Margaret
    Lundell, Marie
    Lubin, Jay H.
    Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies2016In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 185, no 5, 473-484 p.Article in journal (Refereed)
    Abstract [en]

    Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.

  • 36. Veiga, Lene H. S.
    et al.
    Lubin, Jay H.
    Anderson, Harald
    de Vathaire, Florent
    Tucker, Margaret
    Bhatti, Parveen
    Schneider, Arthur
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Inskip, Peter
    Kleinerman, Ruth
    Shore, Roy
    Pottern, Linda
    Holmberg, Erik
    Hawkins, Michael M.
    Adams, M. Jacob
    Sadetzki, Siegal
    Lundell, Marie
    Sakata, Ritsu
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Neta, Gila
    Ron, Elaine
    A Pooled Analysis of Thyroid Cancer Incidence Following Radiotherapy for Childhood Cancer2012In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 178, no 4, 365-376 p.Article in journal (Refereed)
    Abstract [en]

    Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors. (C) 2012 by Radiation Research Society

  • 37. Woltmann, Andrea
    et al.
    Chen, Bowang
    Lascorz, Jesus
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Eyfjord, Jorunn E.
    Hamann, Ute
    Manjer, Jonas
    Enquist-Olsson, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herms, Stefan
    Hoffmann, Per
    Hemminki, Kari
    Lenner, Per
    Forsti, Asta
    Systematic Pathway Enrichment Analysis of a Genome-Wide Association Study on Breast Cancer Survival Reveals an Influence of Genes Involved in Cell Adhesion and Calcium Signaling on the Patients' Clinical Outcome2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, e98229- p.Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWASs) may help to understand the effects of genetic polymorphisms on breast cancer (BC) progression and survival. However, they give only a focused view, which cannot capture the tremendous complexity of this disease. Therefore, we investigated data from a previously conducted GWAS on BC survival for enriched pathways by different enrichment analysis tools using the two main annotation databases Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The goal was to identify the functional categories (GO terms and KEGG pathways) that are consistently overrepresented in a statistically significant way in the list of genes generated from the single nucleotide polymorphism (SNP) data. The SNPs with allelic p-value cut-offs 0.005 and 0.01 were annotated to the genes by excluding or including a 20 kb up-and down-stream sequence of the genes and analyzed by six different tools. We identified eleven consistently enriched categories, the most significant ones relating to cell adhesion and calcium ion binding. Moreover, we investigated the similarity between our GWAS and the enrichment analyses of twelve published gene expression signatures for breast cancer prognosis. Five of them were commonly used and commercially available, five were based on different aspects of metastasis formation and two were developed from meta-analyses of published prognostic signatures. This comparison revealed similarities between our GWAS data and the general and the specific brain metastasis gene signatures as well as the Oncotype DX signature. As metastasis formation is a strong indicator of a patient's prognosis, this result reflects the survival aspect of the conducted GWAS and supports cell adhesion and calcium signaling as important pathways in cancer progression.

1 - 37 of 37
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