Cytochrome P450 1B1 (CYP1B1) and catechol-$O$-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of COMT. The present study was performed to evaluate the associations of CYP1B1 Leu⁴³²Val and/or COMT Val¹⁵⁸Met polymorphisms with total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit statistically significant association with breast cancer risks when analyzed individually, COMT wild type (Val¹⁵⁸Val) in combination with CYP1B1 heterozygous variant (Leu⁴³²Val) [OR: 0.21; 95% CI (0.05–0.82), p value; 0.021] and COMT heterozygous variant (Val¹⁵⁸Met) in combination with CYP1B1 wild type (Leu⁴³²Leu) [OR: 0.29; 95% CI (0.08–0.96), p value; 0.042] showed significant protective association with premenopausal breast cancer risk. The results demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their inverse combination offer protection against breast cancer in premenopausal Indian women.

中文翻译：

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CYP1B1 和 COMT 基因单核苷酸多态性与印度女性乳腺癌易感性的关联。

细胞色素 P450 1B1 (CYP1B1) 和儿茶酚-$O$-甲基转移酶 (COMT) 酶在雌激素代谢中起关键作用。已发现 CYP1B1 和 COMT 酶催化活性的改变与许多人群中绝经后妇女的乳腺癌风险改变有关。密码子 432 处亮氨酸 (Leu) 替换为缬氨酸 (Val) 会增加 CYP1B1 的催化活性，但是，密码子 158 处 Val 替换为甲硫氨酸 (Met) 会降低 COMT 的催化活性。本研究旨在评估 CYP1B1 Leu ⁴³² Val 和/或 COMT Val ¹⁵⁸的关联Met 多态性与印度女性的总体、绝经前和绝经后乳腺癌风险。使用聚合酶链反应限制性片段长度多态性 (PCR-RFLP) 和凝胶电泳分析对照和乳腺癌患者的 COMT 和 CYP1B1 多态性。尽管单独分析时 CYP1B1 和 COMT 基因型与乳腺癌风险没有统计学显着相关性，但 COMT 野生型 (Val ¹⁵⁸ Val) 与 CYP1B1 杂合变异体 (Leu ⁴³² Val) [OR: 0.21; 95% CI (0.05–0.82)，p 值；0.021] 和 COMT 杂合变体（Val ¹⁵⁸ Met）与 CYP1B1 野生型（Leu ⁴³²Leu) [OR: 0.29; 95% CI (0.08–0.96)，p 值；0.042] 显示出与绝经前乳腺癌风险显着的保护性关联。结果表明，CYP1B1 野生型与 COMT 杂合子或其反向组合的组合可为绝经前印度妇女提供预防乳腺癌的保护。