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Joint Effects of the CYP1A1 MspI, ER PvuII, and ER XbaI Polymorphisms on the Risk of Breast Cancer: Results from a Population-Based Case-Control Study in Shanghai, China

¹ School of Radiation Medicine and Public Health, Soochow University, Suzhou, P.R. China; ² Department of Epidemiology and Social Science on Reproductive Health, Shanghai Institute of Planned Parenthood Research, Shanghai, P.R. China; and ³ Division of Research, Kaiser Permanente, Oakland, California

Requests for reprints: Ersheng Gao, Department of Epidemiology and Social Science on Reproductive Health, Shanghai Institute of Planned Parenthood Research, 2140 Xie Tu Road, Shanghai, P.R. China 200032. Phone: 86-21-640-46106; Fax: 86-21-640-46128. E-mail: ersheng_gao{at}yahoo.com.cn

Estrogen-metabolizing gene and estrogen receptor (ER) genes are the possible risk factors implicated in the initiation and development of breast through estrogen tumorigenesis pathway. We examined whether CYP1A1 MspI, ER PvuII, and ER XbaI genetic polymorphisms could increase the risk of breast cancer among Chinese women and gene-gene joint effect on the breast cancer risk in a subset from a population-based case-control study conducted in urban Shanghai from January 1, 1998 and November 31, 2001. PCR-RFLP method based on buccal cells was used to examine the three candidate polymorphisms in 282 breast cancer cases and 298 controls. Compared with CYP1A1 MspI m1/m1, the risk of breast cancer was doubled for genotypes CYP1A1 MspI m1/m2 [odds ratio (OR), 1.83; 95% confidence interval (95% CI), 1.24-2.69] and CYP1A1 MspI m2/m2 (OR, 2.22; 95% CI, 1.26-3.85). The association seemed to be stronger among cases diagnosed older than 45 years and women without a family history of breast cancer. ER PvuII pp and ER XbaI xx polymorphisms, which are in possible linkage disequilibrium, were both associated with a nonsignificantly elevated risk in all subjects; the associations seemed to be stronger among women with a family history of breast cancer. There seems to be a joint effect on the breast cancer risk between CYP1A1 MspI and ER XbaI genotypes (m2/m2 and xx; OR, 5.87; 95% CI, 1.38-24.98), between CYP1A1 MspI and ER PvuII genotypes (m2/m2 and pp; OR, 2.39; 95% CI, 0.81-7.07), and among all three genotypes (m2/m2, pp, and xx; OR, 8.07; 95% CI, 1.45-44.77). Results of this study indicate that estrogen-metabolizing genes and estrogen receptor may jointly play a role in the etiology of breast cancer. (Cencer Epidemiol Biomarkers Prev2006;15(2):342–7)

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