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    Keywords: CANCER ; COHORT ; RISK ; GENE ; ASSOCIATION ; FREQUENCY ; LINKAGE ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; FREQUENCIES ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; PATTERNS ; HEALTH ; WOMEN ; SNP ; PROSPECTIVE COHORT ; prostate cancer ; PROSTATE-CANCER ; cancer risk ; HUMAN GENOME ; REGION ; LINKAGE DISEQUILIBRIUM ; nutrition ; POSTMENOPAUSAL WOMEN ; ONCOLOGY ; ASSOCIATIONS ; RE ; INCREASE ; SNPs ; ESTROGEN ; LEVEL ; ENZYME ; analysis ; HAPLOTYPE ; HAPLOTYPES ; LOCUS ; single-nucleotide ; single-nucleotide polymorphism ; HORMONES ; prospective ; cancer research ; CANCER-RISK ; MULTIETHNIC COHORT ; BASE-LINE CHARACTERISTICS ; PREDICT ; NONCARRIERS ; AROMATASE
    Abstract: The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the final step in the biosynthesis of estrogens. In this study, we used a systematic two-step approach that included gene resequencing and a haplotype-based analysis to comprehensively survey common genetic variation across the CYP19A1 locus in relation to circulating postmenopausal steroid hormone levels and breast cancer risk. This study was conducted among 5,356 invasive breast cancer cases and 7,129 controls comprised primarily of White women of European descent drawn from five large prospective cohorts within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A high-density single-nucleotide polymorphism (SNP) map of 103 common SNPs (〉= 5% frequency) was used to identify the linkage disequilibrium and haplotype patterns across the CYP19A1 locus, and 19 haplotype-tagging SNPs were selected to provide high predictability of the common haplotype patterns. We found haplotype-tagging SNPs and common haplotypes spanning the coding and proximal 5' region of CYP-19A1 to be significantly associated with a 10% to 20% increase in endogenous estrogen levels in postmenopausal women [effect per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 4.4 X 10(-15)]. No significant associations were observed, however, with these SNPs or common haplotypes and breast cancer risk. Thus, although genetic variation in CM19A1 produces measurable differences in estrogen levels among postmenopausal women, the magnitude of the change was insufficient to contribute detectably to breast cancer
    Type of Publication: Journal article published
    PubMed ID: 17325027
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