Abstract
Exposure to sex hormones is a major risk factor for breast cancer and current treatments include hormone modifying drugs, among them aromatase inhibitors. We studied the association of CYP19 (Val(80) and [TTTA](n)) polymorphisms, the gene translated to aromatase, and the risk of breast cancer in BRCA carriers and noncarriers. The study consisted of 958 cancer cases and 931 healthy controls, including 474 carriers and 1,415 noncarriers. Cases and controls came from a population-based study of breast cancer in Israel, enriched with BRCA carriers from a clinical familial cancer service. Val(80) G/G genotype was associated with significantly increased risk of breast cancer compared with the Val(80) A/A genotype in BRCA1 carriers ages <50 years (odds ratio, 2.81; 95% confidence interval, 1.09-7.22; P = 0.032) but not in BRCA2 carriers or noncarriers of any age. A similar magnitude suggestive association, although nonstatistically significant, was found between Val(80) polymorphism and estrogen receptor-negative status of the breast tumors. A common haplotype composed of the Val(80) G allele and three haplotype-tagging single nucleotide polymorphisms (rs727479, rs10046, and rs4646) in the CYP19 coding region showed a trend to association with breast cancer risk in BRCA1 carriers ages <50 years. Published expression data show higher estrogen levels with higher repeats in [TTTA](n) found in linkage disequilibrium with Val(80). The present study suggests that the CYP19 Val(80) polymorphism and a haplotype that includes this polymorphism are associated with increased breast cancer risk in young women with BRCA1 mutations.
Highlights
Breast cancer is one of the leading causes of cancer morbidity and mortality worldwide [1]
The present study suggests that the CYP19 Val80 polymorphism and a haplotype that includes this polymorphism are associated with increased breast cancer risk in young women with BRCA1 mutations. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1617 – 23)
In all BRCA1 mutation carriers, CYP19 Val80 was not associated with breast cancer risk (OR per G allele increase, 1.17; 95% confidence intervals (95% CI), 0.83-1.63; P = 0.370)
Summary
Breast cancer is one of the leading causes of cancer morbidity and mortality worldwide [1]. Estimates of penetrance vary greatly across different studies, ranging from 37% to 90% [6,7,8,9,10,11,12] This heterogeneity in risk among women who carry BRCA1/2 mutations suggests the existence of modifying genetic and/or environmental factors. Polymorphisms in several genes have been suggested to modify breast and ovarian cancer risk in BRCA1 and BRCA2 carriers, most have not been replicated [13,14,15,16,17,18,19,20,21]. As yet, evaluated the association between polymorphisms in the genes involved in estrogen metabolism and breast cancer risk in BRCA mutation carriers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
