摘要
目的探讨ER-α基因PvuⅡ和XbaⅠ多态性在上海地区无BRCA1／BRCA2基因突变的有遗传倾向的乳腺癌人群中的分布及其与乳腺癌发病风险的相关性。方法对113例无BRCA1／2突变的家族性／早发性乳腺癌患者和113例正常对照者进行ER-α基因2号内含子的聚合酶链反应扩增,随后进行DNA直接测序鉴定PvuⅡ和XbaⅠ多态性的基因型,比较基因型分布和发病风险的关系;危险度OR及95％CI,应用非条件Logistic回归分析计算。结果113例病例和113例对照均成功进行测序,ER-α基因PvuⅡ多态性的CC、CT、TT基因型在病例组中的分布频率分别为16例(14．2％),58例(51．3％),39例(34．5％);XbaⅠ多态性AA、AG、GG基因型在病例组中的分布频率分别为76例(67．2％),34例(30．1％),3例(2．7％)。分别以CC基因型和AA基因型为参照,PvuⅡ和XbaⅠ多态性与乳腺癌无明显关联;但在绝经前妇女中,PvuⅡ多态性的C／T基因型提高乳腺癌发病风险达2．1倍(P=0．044);XbaⅠ多态的GG基因型携带者患乳腺癌发病危险降低达9倍(OR= 0．11,P=0．058)。基因型的联合分析表明,与CC+GG基因型相比,同时携带PvuⅡCT和XbaⅠAA的绝经前妇女患乳腺癌的发病危险增加达11倍(OR=11．4;95％CI 1．12-116．7),P=0．03。结论ER-α基因PvuⅡ和XbaⅠ多态性可能与有遗传倾向乳腺癌的遗传易感性有关,尤其是绝经前发病者(含早发性)。
Objective The present study was to explore association of Pvu Ⅱ and Xba Ⅰ polymorphism in ER-α gene with genetic susceptibility for breast cancer without BRCA1/2 gene mutation. Methods 113 BRCA1/2 negative hereditary breast cancer patients from independent families and 113 agematched healthy control subjects were analyzed. Genotype analysis was conducted by polymerase chain reaction （PCR） and then DNA direct sequencing. The odd-ratios （OR） and 95% confidence intervals （CI） was calculated by unconditional logistic regression model. Results The frequency of Pvu Ⅱ polymorphism CC（PP） ,CT（Pp） ,TT（pp） genotype in patients was found in 16 cases（ 14. 2% ） , 58 cases（51.3% ） , and 39 cases （ 34. 5 % ）. The distribution of AA （xx） , AG （Xx） , GG （ XX ） genotype of Xba Ⅰ polymorphism were found in 76 cases （67.2%）, 34 eases （30.1%）, and 3 cases （2.7%） among patients. Among premenopausal women, CT genotype of Pvu Ⅱ confered a significantly increased risk for breast cancer compared with CC genotype （ adjusted OR = 2.07 ; 95 % CI, 0. 68 ～ 6. 30） ; Carriers of GG of Xba Ⅰ had a decreased risk for breast cancer （ adjusted OR = O. 11 ; 95% CI, 0. 01 ～ 1.27 ） compared with AA genotype. Furthermore, combined analysis of two polymorphisms indicated individuals carrying Pvu Ⅱ CT and Xba Ⅰ AA genotype were at increased risk for breast cancer as compared with those with Pvu Ⅱ CC and Xba Ⅰ GG genotype（ OR = 11.43, 95% CI, 1.12 - 116. 7 ） among premenopausal women. Conclusions Pvu Ⅱ and Xba Ⅰ polymorphisms in ER-α gene could be a candidate locus for low penetrance breast cancer susceptibility in Chinese population, especially among premenopausal women.
出处
《中华普通外科杂志》
CSCD
北大核心
2006年第9期637-640,共4页
Chinese Journal of General Surgery
基金
国家自然科学基金资助项目(30371580)
国家"十五"攻关项目(2002AA711A08)
上海市科委重点项目(03JC14019)
复旦大学研究生创新基金(CQF000812)
关键词
乳腺肿瘤
雌激素受体Α
疾病遗传易感性
多态现象
遗传
Breast neoplasms
Estrogen receptor alpha
Genetic susceptibility to disease
Polymorphism, genetic
