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A multigenic study on breast cancer risk associated with genetic polymorphisms of ER Alpha, COMT and CYP19 gene in BRCA1/BRCA2 negative Shanghai women with early onset breast cancer or affected relatives

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Abstract

High penetrance genes such as BRCA1 or BRCA2 account for only a small proportion of familial breast cancer in Chinese population. Estrogen has been proposed to participate in the proliferation and carcinogenesis of breast cancer. To investigate the association between genetic polymorphisms in genes encoding estrogen metabolizing, estrogen biosynthesizing enzyme and estrogen receptor and the breast cancer risk in BRCA1/BRCA2 negative Shanghai women, we conducted a case-control study including 114 cases with early-onset breast cancer or affected relatives and 121 healthy controls. The genotypes of estrogen receptor alpha (ERα), aromatase (CYP19), and catechol-O-methyltransferase (COMT) genes were analyzed by direct DNA-sequencing. Compared with H/H genotype of COMT Val158Met, COMT Val158Met L/L genotype was associated with a nonsignificantly elevated risk of breast cancer (OR: 3.72; 95% CI: 0.99–13.96, P = 0.051). There was no statistically significant difference in genotype frequency of the ERα PvuII, ERα XbaI and CYP19 Arg264Cys polymorphism between controls and cases. When stratified by menopausal status, COMT Val158Met L/L (OR: 11.94; 95% CI: 1.48–96.03, P = 0.02) and ERα PvuII P/p genotypes (OR: 2.67; 95% CI: 1.01–7.05, P = 0.048) were associated with a significantly elevated risk of breast cancer in premenopausal women, and there was a association between ERα XbaI x/x genotype and the nonsignificantly increased risk of breast cancer in premenopausal women (OR: 6.88; 95% CI: 0.80–59.15, P = 0.079). The multigenic analysis showed maybe these high risk genotypes had combined effect on breast cancer risk. Our findings suggest that polymorphism of genes involving estrogen-metabolizing pathway, estrogen- biosynthesizing pathway and estrogen receptor pathway may play an important role in the etiology of BRCA1/2 negative breast cancer with hereditary predisposing factors.

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Acknowledgment

This research was supported in part by the Outstanding Young Investigator Award of National Natural Science Foundation of China (30025015), National Key Project of China (2001BA703BO5), National Natural Science Foundation of China (30371580, 30572109, 30570695), the Grant from Shanghai Science and Technology Committee (03J14019, 32R14021) and the Young Investigator Award of Fudan University (JKF159002).

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Authors and Affiliations

  1. Breast Cancer Institute, Cancer Hospital, Department of Oncology, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Zhen Hu, Chuan-Gui Song, Jing-Song Lu, Jian-Min Luo, Zhen-Zhou Shen & Zhi-Ming Shao

  2. Department of Oncology, Affiliated Union Hospital, Fujian Medical University, Fuzhou, Fujian, 350001, China

    Chuan-Gui Song

  3. Chinese National Human Genome Center at Shanghai, Shanghai, 201203, China

    Wei Huang

  4. Department of Breast Surgery, Cancer Hospital/Cancer Institute, Breast Cancer Institute, Fudan University, 399 Ling-Ling Road, Shanghai, 200032, People’s Republic of China

    Zhi-Ming Shao

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  1. Zhen Hu
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  2. Chuan-Gui Song
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Correspondence to Zhi-Ming Shao.

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Zhen Hu and Chuan-Gui Song contributed equally to the work.

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Hu, Z., Song, CG., Lu, JS. et al. A multigenic study on breast cancer risk associated with genetic polymorphisms of ER Alpha, COMT and CYP19 gene in BRCA1/BRCA2 negative Shanghai women with early onset breast cancer or affected relatives. J Cancer Res Clin Oncol 133, 969–978 (2007). https://doi.org/10.1007/s00432-007-0244-7

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  • DOI: https://doi.org/10.1007/s00432-007-0244-7

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