Thota Kanakaiah, Prasad K, Basaveswara Rao Mandava V
Department of Pharmacology, Krishna University, Rajupeta, Machilipatnam, India. Email:
Asian Pac J Cancer Prev. 2018 Feb 26;19(2):343-350. doi: 10.22034/APJCP.2018.19.2.343.
Background: Breast cancer is the most common cancer among women worldwide. Tamoxifen (TAM), a selective estrogen receptor modulator, is widely used in its treatment. TAM is metabolized by cytochrome P450 (CYP450) enzymes, including CYP2D6, CYP3A5 and CYP2C19, whose genetic variations may have clinicopathological importance. However, reports on the association of various P450 polymorphisms with certain cancers are contradictory. Methods: We here investigated whether the prevalence of the four most common polymorphism in the CYP2D64 (G1934A), CYP2D610 (C188T), CYP3A53 and CYP2C192 alleles has any link with breast cancer using genomic DNA and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Prevalences of CYP2D64, CYP2D610 and CYP2C192 genotypes were differed significantly (P = 0.01 and P = 0.004) between breast cancer patients and controls. The CYP3A53 genotype did not demonstrate statistically significant variation. Conclusion: Polymorphisms in CYP2 appear to be associated with breast cancer risk. Our data taken together with other reports indicates that drug resistance gene polymorphisms might be indicators of response to tamoxifen therapy in breast cancer cases.
乳腺癌是全球女性中最常见的癌症。他莫昔芬(TAM),一种选择性雌激素受体调节剂,被广泛用于其治疗。TAM由细胞色素P450(CYP450)酶代谢,包括CYP2D6、CYP3A5和CYP2C19,其基因变异可能具有临床病理意义。然而,关于各种P450多态性与某些癌症关联的报道相互矛盾。方法:我们在此使用基因组DNA和聚合酶链反应限制性片段长度多态性(PCR-RFLP)分析,研究CYP2D64(G1934A)、CYP2D610(C188T)、CYP3A53和CYP2C192等位基因中四种最常见多态性的患病率是否与乳腺癌有任何关联。结果:乳腺癌患者与对照组之间,CYP2D64、CYP2D610和CYP2C192基因型的患病率存在显著差异(P = 0.01和P = 0.004)。CYP3A53基因型未显示出统计学上的显著差异。结论:CYP2中的多态性似乎与乳腺癌风险相关。我们的数据与其他报道一起表明,耐药基因多态性可能是乳腺癌病例中他莫昔芬治疗反应的指标。