中文摘要：

目的探讨Catechol-O-methyhransferase（COMT）基因Val158Met（G→A）多态性在BRCA1／BRCA2基因无突变的具有遗传倾向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114例无BRCA1／BRCA2突变的家族性或早发性乳腺癌患者和121例正常对照者进行COMT基因第4外显子的聚合酶链反应扩增，随后进行DNA直接测序鉴定Val158Met多态的基因型，比较基因型分布和发病风险的关系；相对危险比值比（oddratio，OR）及95％可信区间（confidence interval，CI）应用非条件Logistic回归分析计算。结果COMT基因Val158Met多态的GG，GA和AA基因型在病例组中的分布频率分别为0．58（65例），0．32（36例）和0．10（11例）；在对照组的分布频率分别为0．60（66例），0．37（41例）和0．03（3例）。在早发性乳腺癌人群中，含A基因型的频率为0．57（21例），显著高于家族性乳腺癌的0．35（26例）（P=0．026）。以GG基因型为参照，AA基因型（158Met）显著提高了乳腺癌的发病危险（OR=3．15；95％CI：0．70～14．19）（P=0．039），在绝经前妇女尤为明显（OR=9．98；95％CI：1．00～99．64）（P=0．004）；在体质指数（body mass index，BMI）≤23kg／m^2的妇女中，AA纯合基因型（158Met）临界显著提高了乳腺癌的发病危险（OR=7．57；95％CI：0．57～101．28）（P=0．056）。结论COMT基因Val158Met可能与乳腺癌、特别是绝经前或早发性乳腺癌的遗传易感性有关，可作为低外显率的乳腺癌易感基因位点。

英文摘要：

Objective To explore the prevalence of Val158Met polymorphism in Catechol-O- methyhransferase（COMT） gene and its effect on genetic susceptibility for breast cancer in Shanghai population. Methods A total of 114 patients with BRCA1/BRCA 2 negative hereditary breast cancer from independent families and 121 age-matched healthy controls 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） were calculated by unconditional logistic regression model. Results The frequency of Val158Met polymorphism GG, GA and AA genotype in case group and control was 0. 58 （65） , 0. 32 （36）, 0. 10 （ 11 ） and 0. 60 （ 66 ）, 0. 35 （41）, 0. 03 （ 3 ） , respectively. The frequency of allelecontaining genotypes is significantly higher in early-onset breast cancer patients （0. 57 ） than in familial ones （0. 35 ）. Compared with GG（Val/Val） genotype, AA （Met/Met） genotype confers a significantly increased risk for breast cancer （ adjusted OR = 3.15 ; 95% CI, 0. 70 - 14. 19 ） , especially among premenopausal women （ adjusted OR = 9. 98 ; 95% CI, 1.00 - 99. 64 ）. Borderline significantly association was found between AA genotype （ adjusted OR = 7.57 ; 95% CI, 0. 57 - 101.28 ） and susceptibility for breast cancer in BMI ≤23 kg/m^2 group. Conclusions Val158Met polymorphism in COMT gene could be a candidate for low penetrance breast cancer susceptibility in Shanghai population, especially among premenopausal women and early-onset breast cancer patients.