Polymorphisms in Steroid Hormone Biosynthesis Genes and Risk of Breast Cancer and Fibrocystic Breast Conditions in Chinese Women

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2008-05, Vol.17 (5), p.1066-1073
• Main Authors: Sakoda, Lori C, Blackston, Christie, Doherty, Jennifer A, Ray, Roberta M, Lin, Ming Gang, Stalsberg, Helge, Gao, Dao Li, Feng, Ziding, Thomas, David B, Chen, Chu
• Format: Article
• Language: English
• Subjects: Adult; Aged; Asian Continental Ancestry Group - genetics; breast cancer; Breast Neoplasms - ethnology; Breast Neoplasms - genetics; Case-Control Studies; China; Cholesterol Side-Chain Cleavage Enzyme - genetics; CYP11A1; CYP17A1; Estradiol Dehydrogenases - genetics; Female; fibrocystic breast conditions; Fibrocystic Breast Disease - genetics; Gene Frequency; Genetic Predisposition to Disease; genetic susceptibility; Genotype; HSD17B1; Humans; Logistic Models; Middle Aged; polymorphism; Polymorphism, Genetic; Risk Factors; sex steroid hormones; Steroid 17-alpha-Hydroxylase - genetics
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-07-2680

Common variants in genes encoding for key enzymes involved in steroidogenesis may alter sex steroid hormone levels, thereby influencing susceptibility to breast carcinoma and related conditions. In a case-control study of Chinese women, we examined genotypes of the CYP11A1 pentanucleotide [(TAAAA) n ] repeat (D15S520), CYP17A1 rs743572, and HSD17B1 rs605059 polymorphisms in relation to the risk of breast cancer and fibrocystic breast conditions, comparing 615 women with breast cancer and 467 women with fibrocystic breast conditions separately with 879 women without clinical breast disease. We also evaluated whether these relationships differed by the presence of proliferation in the extratumoral epithelium or fibrocystic lesions, menopausal status, or body mass index. Only CYP11A1 genotype was related to breast cancer risk, with women homozygous for the 4-repeat allele, relative to those homozygous for the 6-repeat allele, at reduced risk (age-adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.91). There was some suggestion of a stronger inverse association for breast cancer with evidence of proliferation in the extratumoral epithelium than for breast cancer without extratumoral proliferation. Breast cancer risk associated with CYP11A1 genotype did not differ by menopausal status or body mass index level. No associations between CYP11A1, CYP17A1 , and HSD17B1 genotypes and risk of fibrocystic breast conditions were observed. Our findings support the possibility that common allelic variation at the CYP11A1 D15S520 locus alters breast cancer risk in Chinese women. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1066–73)