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
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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DOI：
10.1007/s00432-007-0244-7
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发表时间：
2007-12-01
影响因子：
3.6
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Hu, Zhen;Song, Chuan-Gui;Shao, Zhi-Ming
BRCA 1、BRCA 2等高表达基因在中国家族性乳腺癌中仅占很小比例。雌激素被认为参与了乳腺癌的增殖和癌变过程。为探讨雌激素代谢、雌激素生物合成酶和雌激素受体基因多态性与BRCA 1/BRCA 2阴性上海女性乳腺癌发病风险的关系，采用病例对照研究方法，对114例早发性乳腺癌患者及其亲属和121名健康对照进行研究。通过直接DNA测序分析雌激素受体α（ER α）、芳香化酶（CYP 19）和儿茶酚-O-甲基转移酶（COMT）基因的基因型。与COMT Val 158 Met的H/H基因型相比，COMT Val 158 Met L/L基因型与乳腺癌的发生风险无显著性差异（OR：3.72，95%CI：0.99-13.96，P = 0.051）。ER α PvuII、ER α XbaI和CYP 19 Arg 264 Cys多态性基因型频率在对照组和病例组之间无统计学差异。按绝经状态分层时，COMT Val 158 Met L/L（OR：11.94; 95%CI：1.48-96.03，P = 0.02）和ER α PvuII P/p基因型（OR：2.67; 95% CI：1.01-7.05，P = 0.048）与绝经前妇女患乳腺癌的风险显著升高相关，ER α XbaI x/x基因型与绝经前妇女患乳腺癌的风险无显著性相关（OR：6.88，95% CI：0.80-59.15，P = 0.079）。多基因分析表明，这些高危基因型可能对乳腺癌的发生有联合作用。提示雌激素代谢途径、雌激素生物合成途径和雌激素受体途径基因多态性在BRCA 1/2阴性乳腺癌的遗传易感因素中可能起重要作用。
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.