Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India.
Department of Medical and Paediatric Oncology, Dr.G.V.N Cancer Institute, Singarathope, Trichy, 620 008, India.
Breast Cancer Res Treat. 2021 Apr;186(3):823-837. doi: 10.1007/s10549-020-06028-z. Epub 2021 Jan 4.
Functional variants of the xenobiotic-metabolizing genes (XMG) might modulate breast cancer (BC) risk by altering the rate of metabolism and clearance of myriad types of potent carcinogens from the breast tissue. Despite mounting evidence on the role of XMG variants on BC risk, the current knowledge regarding their influence on BC development is still fragmentary.
The present study examined the candidate genetic variants in CYP1A1, NQO1, GST-T1, GST-M1, and GST-P1 in 1002 subjects (502 BC patients and 500 disease-free women). PCR-RFLP was employed to genotype the mono-nucleotide variation in CYP1A1, NQO1, and GST-P1, and allele-specific PCR was used to detect the deletion polymorphism in GST-T1 and GST-M1 genes.
Regarding CYP1A1-M1 polymorphism, the heterozygous TC and mutant CC genotype conferred 1.47-fold (95% CI 1.13-1.91, p = 0.004) and 1.84-fold (95% CI 1.17-2.91, p = 0.009) elevated risk of BC. GST-T1 null genotype was associated with increased BC risk (OR 1.47; 95% CI 1.02-2.11, p = 0.037). For the NQO1 C609T variant, the mutant T allele was associated with BC risk with an odds ratio of 1.22 (95% CI 1.02-1.48, p = 0.034). Combinatorial analysis indicated that the presence of NQO1*2 (CT), CYP1A1-M1 (CC), and GST-P1 rs1695 (AG) genotypes conferred 16.7-fold elevated risk of BC (95% CI 3.65-76.85; p < 0.001). Moreover, GST-M1 null genotype was associated with the development of larger primary breast tumors.
Xenobiotic-metabolizing gene polymorphisms may play a crucial role in mammary carcinogenesis in South Indian women.
外源性代谢基因（XMG）的功能变体可能通过改变乳腺组织中多种强效致癌物的代谢和清除率来调节乳腺癌（BC）的风险。尽管越来越多的证据表明 XMG 变体对 BC 风险的作用，但关于它们对 BC 发展的影响的现有知识仍然很零碎。
本研究在 1002 名受试者（502 名 BC 患者和 500 名无病女性）中检测了 CYP1A1、NQO1、GST-T1、GST-M1 和 GST-P1 中的候选遗传变异。PCR-RFLP 用于检测 CYP1A1、NQO1 和 GST-P1 中的单核苷酸变异，等位基因特异性 PCR 用于检测 GST-T1 和 GST-M1 基因中的缺失多态性。
关于 CYP1A1-M1 多态性，杂合 TC 和突变 CC 基因型赋予 BC 风险 1.47 倍（95%CI 1.13-1.91，p=0.004）和 1.84 倍（95%CI 1.17-2.91，p=0.009）。GST-T1 无效基因型与 BC 风险增加相关（OR 1.47；95%CI 1.02-2.11，p=0.037）。对于 NQO1 C609T 变体，突变 T 等位基因与 BC 风险相关，比值比为 1.22（95%CI 1.02-1.48，p=0.034）。组合分析表明，NQO1*2（CT）、CYP1A1-M1（CC）和 GST-P1 rs1695（AG）基因型的存在赋予 BC 风险 16.7 倍的升高（95%CI 3.65-76.85；p<0.001）。此外，GST-M1 无效基因型与原发性乳腺癌的发生相关，并且与较大的原发性乳腺癌肿瘤的发生相关。
外源性代谢基因多态性可能在南印度妇女的乳腺癌发生中起关键作用。
