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

被引:29
作者
Hu, Zhen
Song, Chuan-Gui
Lu, Jing-Song
Luo, Jian-Min
Shen, Zhen-Zhou
Huang, Wei
Shao, Zhi-Ming
机构
[1] Fudan Univ, Breast Canc Inst, Canc Hosp Canc Inst, Dept Breast Surg, Shanghai 200032, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai Med Coll,Dept Oncol, Canc Hosp,Breast Canc Inst, Shanghai 200032, Peoples R China
[3] Fujian Med Univ, Union Hosp, Dept Oncol, Fujian 350001, Peoples R China
[4] Chinese Natl Human Genome Ctr, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
breast cancer; BRCA1 and BRCA2 gene; ER alpha; CYP19; COMT; genetic polymorphism;
D O I
10.1007/s00432-007-0244-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (ER alpha), 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 ER alpha PvuII, ER alpha 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 ER alpha 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 ER alpha 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.
引用
收藏
页码:969 / 978
页数:10
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