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Sökning: WFRF:(Kast K) > (2015-2019) > Lunds universitet

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  • Ferreira, MA, et al. (författare)
  • Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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  • Schrijver, L, et al. (författare)
  • Oral contraceptive use and breast cancer risk: A cohort study of BRCA1 and BRCA2 mutation carriers
  • 2017
  • Ingår i: Cancer Research. - 1538-7445. ; 77:13 Suppl 1
  • Konferensbidrag (refereegranskat)abstract
    • Background: BRCA1 and BRCA2 mutation carriers are at high risk of breast and ovarian cancer. Oral contraceptive preparations (OCPs) may reduce ovarian cancer risk, but its effect on breast cancer risk remains unclear. Methods: Combined data from three cohorts of 5705 BRCA1 and 3521 BRCA2 mutation carriers (IBCCS, BCFR and kConFab) were analyzed using age-dependent Cox regression models stratified for study and birth cohort. We conducted the first prospective analyses on this topic. Our additional main retrospective analyses were leftcensored 5 years preceding date of baseline questionnaire to control for survival bias. The full-cohort retrospective analyses, without left-censoring, was performed to compare results with the literature. Prospective analyses were considered most valid, while retrospective analyses were most powerful. Results: For BRCA1 mutation carriers we found no association between ever OCP use and risk of breast cancer in the prospective analyses (HR=1.08, 95% CI 0.75-1.56), but 23% and 27% increased risks for ever OCP use in the left-censored and full retrospective analyses, respectively. Retrospectively, an increasing trend for longer duration of use, especially before first full-term pregnancy (FFTP) was found (left-censored analyses: 10 years HR 1.41 (95%CI 1.10-1.813), p-trend=0.001 for duration of use before FFTP). For BRCA2 mutation carriers we found a positive association between ever OCP use and risk of breast cancer prospectively (HR=1.75, 95% CI 1.03-2.97), but retrospectively findings were inconsistent (HR=1.06, 95% CI 0.85-1.33 and HR=1.52, 95% CI 1.28-1.81 for the left-censored and full analyses, respectively). Conclusion: For BRCA1 mutation carriers the discrepancy between results of prospective and retrospective analyses may be explained by time since last OCP use before FFTP. Thus, a temporal increased risk of breast cancer following longer duration of OCP use before FFTP cannot be ruled out. The discordant findings between prospective and retrospective analyses for BRCA2 carriers could not be explained. Because of the lack of scientific clarity it is too early to give an unequivocal advice on OCP use with respect to breast cancer risk to BRCA1 and BRCA2 mutation carriers.
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