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目的探讨 Catechol-O-methyltransferase(COMT)基因 Vall58Met(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 Vall58Met 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(odd ratio,OR)及95%可信区间(confidenceinterval,CI)应用非条件 Logistic回归分析计算。结果 COMT 基因 Vall58Met 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)≤23 kg/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 Vall58Met 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。
Objective To investigate the distribution of Vall58Met (G → A) polymorphism of Catechol-O-methyltransferase (COMT) gene in breast cancer patients with genetic predisposition without mutation of BRCA1 / BRCA2 gene and its association with the risk of breast cancer. METHODS: One hundred and forty-four patients with familial or early-onset breast cancer without BRCA1 / BRCA2 mutation and 121 normal controls were enrolled in the polymerase chain reaction amplification of exon 4 of COMT gene. DNA sequence was subsequently used to identify Vall58Met polymorphism The genotype distribution of genotypes was compared with the risk of morbidity. Odds ratio (OR) and 95% confidence interval (CI) were compared using unconditional logistic regression analysis. Results The distribution frequencies of COMT gene Vall58Met polymorphism in GG, GA and AA genotypes were 0.58 (65 cases), 0.32 (36 cases) and 0.10 (11 cases) in the case group, respectively (66 cases), 0.37 (41 cases) and 0.03 (3 cases). In early-onset breast cancer, the frequency of genotype A was 0.57 (n = 21), significantly higher than that of familial breast cancer (n = 26) (p = 0.026). The genotype AA (158 Met) significantly increased the risk of breast cancer (OR = 3.15; 95% CI: 0.70-14.19) (P = 0.039), especially in premenopausal women (OR = 9.98 ; 95% CI: 1.00 to 99.64) (P = 0.004). In women with body mass index (BMI) ≤23 kg / m ~ 2, the AA homozygous genotype (158 Met) (OR = 7.57; 95% CI: 0.57 to 101.28) (P = 0.056). Conclusion The COMT gene Vall58Met may be associated with the genetic predisposition of breast cancer, especially pre-menopausal or early-onset breast cancer, and may be used as low-penetrance breast cancer susceptibility loci.