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Sökning: WFRF:(Kast K)

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  • Föregående 123[4]5Nästa
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31.
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37.
  • 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. - : American Association for Cancer Research Inc.. - 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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38.
  • Hemminki, Kari, et al. (författare)
  • Low-risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer patients
  • 2010
  • Ingår i: International Journal of Cancer. - : John Wiley and Sons. - 0020-7136. ; 126:12, s. 2858-2862
  • Tidskriftsartikel (refereegranskat)abstract
    • To validate common low-risk variants predisposing for breast cancer (BC) in a large set of BRCA1/2 negative familial or genetically enriched cases from Germany, we genotyped 1,415 cases and 1,830 healthy women by MALDI-TOF in 105 candidate SNPs. Significantly higher ORs than previously reported for heterozygous unselected cases were found for the minor allele in FGFR2 (OR = 1.43, 95% Cl 1.30-1.59, p-value = 1.24 x 10(-12)) and for TNRC9 (OR = 1.33, 95% Cl 1.19-1.46, p-value = 1.54 x 10(-7)). Most intriguing, however, were the ORs for homozygous carriers from high-risk families for FGFR2 (OR = 2.05, 95% Cl 1.68-2.51, LSP1 (OR = 0.49, 95% Cl 0.28-0.86) and TNRC9 (OR = 1.62, 95% Cl 1.27-2.07). Moreover, the additional validation of 99 CGEMS-SNPs identified putative novel susceptibility alleles within the LSP1 gene (OR = 0.73, 95% Cl 0.61-0.87, p-value = 5.23 x 10(-4)). Finally, we provide evidence for the first time that a low-risk variant located at 6q22.33 (rs6569479) is associated with estrogen receptor negative BC in familial cases (OR = 1.33, 95% Cl 1.06-1.66; p-value = 0.012). Our data confirm the impact of the previously identified susceptibility loci and provide preliminary evidence for novel susceptibility loci in familial BC cases and correlate them to specific histopathological subtypes defined by estrogen receptor status.
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40.
  • Mulligan, Anna Marie, et al. (författare)
  • Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2.
  • 2011
  • Ingår i: Breast cancer research : BCR. - 1465-542X. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumor. METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumor, to assess the associations of twelve loci with breast cancer tumor characteristics. Associations were evaluated using a retrospective cohort approach. RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for eleven loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, SNP rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele HR for ER-positive=1.35, 95%CI:1.17-1.56 vs HR=0.91, 95%CI:0.85-0.98 for ER-negative, P-heterogeneity=6.5e-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. CONCLUSIONS: The associations of the twelve SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumor subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.
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