Sangalli Antonella, Orlandi Elisa, Poli Albino, Maurichi Andrea, Santinami Mario, Nicolis Morena, Ferronato Silvia, Malerba Giovanni, Rodolfo Monica, Gomez Lira Macarena
aDepartment of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics bDepartment of Diagnostics and Public Health, University of Verona, Verona cMelanoma and Sarcoma Surgery Unit dUnit of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Melanoma Res. 2017 Aug;27(4):309-314. doi: 10.1097/CMR.0000000000000360.
The genetics of melanoma is complex and, in addition to environmental influences, numerous genes are involved or contribute toward melanoma predisposition. In this study, we evaluated the possible interaction between miR-146a and one of its putative targets ribonuclease L (RNASEL) in the risk of sporadic melanoma. Polymorphisms rs2910164 in miR-146a and rs486907 in the RNASEL gene have both independently been associated with the risk of different cancers, and an interaction between them has been observed in nonmelanoma skin cancer. Polymorphisms rs2910164 G/C and rs486907 A/G were genotyped by restriction fragment length polymorphism analysis in 304 sporadic melanoma patients and 314 control individuals. Genotype distribution between cases and controls for each of the two polymorphisms was compared using Fisher's exact test. Epistasis between the two polymorphisms was tested by a logistic regression model. In the present study, we observed a sex-specific effect of the miR-146a rs2910164 C allele restricted to individuals carrying the RNASEL rs486907 A allele as well. Men carrying this allelic combination have the highest risk of melanoma, whereas it seems to have no effect or even an opposite relationship to melanoma risk in the female population. The results reported in the present study suggest a sex-specific interaction between miR-146a and RNASEL genes in melanoma skin cancer susceptibility, and could account for possible discordant results in association studies when stratification according to sex is not performed.
黑色素瘤的遗传学很复杂，除环境影响外，众多基因参与其中或导致黑色素瘤易感性。在本研究中，我们评估了miR-146a与其假定靶标之一核糖核酸酶L（RNASEL）之间可能的相互作用对散发性黑色素瘤风险的影响。miR-146a中的多态性rs2910164和RNASEL基因中的rs486907均独立地与不同癌症的风险相关，并且在非黑色素瘤皮肤癌中观察到它们之间的相互作用。通过限制性片段长度多态性分析对304例散发性黑色素瘤患者和314例对照个体进行了rs2910164 G/C和rs486907 A/G多态性基因分型。使用Fisher精确检验比较了两种多态性在病例组和对照组之间的基因型分布。通过逻辑回归模型检验了两种多态性之间的上位性。在本研究中，我们观察到miR-146a rs2910164 C等位基因的性别特异性效应，该效应也仅限于携带RNASEL rs486907 A等位基因的个体。携带这种等位基因组合的男性患黑色素瘤的风险最高，而在女性人群中，它似乎对黑色素瘤风险没有影响，甚至有相反的关系。本研究报告的结果表明，miR-146a和RNASEL基因在黑色素瘤皮肤癌易感性中存在性别特异性相互作用，这可以解释在未按性别分层的关联研究中可能出现的不一致结果。
