Nallapalle Sateesh Reddy, Daripally Sarika, Prasad V T S Vidudala
Research and Development, Basavatarakam Indo-American Cancer Hospital and Research Institute (BIACH&RI), Road No. 10, Banjara Hills, Hyderabad, 500034, India.
Tumour Biol. 2015 Apr;36(4):2709-24. doi: 10.1007/s13277-014-2896-7. Epub 2014 Dec 4.
We investigated risk association of FAS (-1377 G>A and -670 A>G) and FASL (-844 T>C) promoter polymorphisms with breast, ovarian, cervical, and endometrial cancers and report that the FASL -844 CC genotype was protective against breast, ovarian, cervical, and endometrial cancers (P ≤ 0.01). On the other hand, FAS -1377 GA and AA variants increased risk of breast cancer. However, the GA variant of FAS -1377 was also found to be a risk factor for cervical cancer. In contrast, FAS -670 AG variant significantly lowered risk of breast cancer. Further, we also observed that risk association of co-occurrence of FAS and/or FASL variants with the cancers varied as compared to the presence of individual polymorphisms. Although risk and protective haplotypes of FAS SNPs were observed across the cancer phenotypes, the association of the haplotypes was significant for breast cancer alone with a 3-fold enhanced risk. The protective effect of the FASL CC genotype seen in this study suggests that similar biomolecular mechanisms involving FASL might play a role in female-specific cancers.
我们研究了FAS基因（-1377 G>A和-670 A>G）及FASL基因（-844 T>C）启动子多态性与乳腺癌、卵巢癌、宫颈癌和子宫内膜癌的风险关联，并报告FASL -844 CC基因型对乳腺癌、卵巢癌、宫颈癌和子宫内膜癌具有保护作用（P≤0.01）。另一方面，FAS -1377 GA和AA变异增加了乳腺癌风险。然而，FAS -1377的GA变异也被发现是宫颈癌的一个风险因素。相比之下，FAS -670 AG变异显著降低了乳腺癌风险。此外，我们还观察到，与单个多态性存在相比，FAS和/或FASL变异共同出现与癌症的风险关联有所不同。尽管在各种癌症表型中均观察到FAS单核苷酸多态性的风险和保护单倍型，但单倍型关联仅在乳腺癌中显著，风险增加了3倍。本研究中观察到的FASL CC基因型的保护作用表明，涉及FASL的类似生物分子机制可能在女性特异性癌症中发挥作用。
