Wu Wenting, Liu Hongliang, Song Fengju, Chen Li-Shiun, Kraft Peter, Wei Qingyi, Han Jiali
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA.
Duke Cancer Institute, Duke School of Medicine, Durham, North Carolina, USA.
Oncotarget. 2016 Jul 26;7(30):47366-47375. doi: 10.18632/oncotarget.10144.
Several studies have reported that cigarette smoking is inversely associated with the risk of melanoma. This study further tested whether incorporating genetic factors will provide another level of evaluation of mechanisms underlying the association between smoking and risk of melanoma. We investigated the association between SNPs selected from genome-wide association studies (GWAS) on smoking behaviors and risk of melanoma using 2,298 melanoma cases and 6,654 controls. Among 16 SNPs, three (rs16969968 [A], rs1051730 [A] and rs2036534 [C] in the 15q25.1 region) reached significance for association with melanoma risk in men (0.01 < = P values < = 0.02; 0.85 < = Odds Ratios (ORs) <= 1.20). There was association between the genetic scores based on the number of smoking behavior-risk alleles and melanoma risk with P-trend = 0.005 among HPFS. Further association with smoking behaviors indicating those three SNPs (rs16969968 [A], rs1051730 [A] and rs2036534 [C]) significantly associated with number of cigarettes smoked per day, CPD, with P = 0.009, 0.011 and 0.001 respectively. The SNPs rs215605 in the PDE1C gene and rs6265 in the BDNF gene significantly interacted with smoking status on melanoma risk (interaction P = 0.005 and P = 0.003 respectively). Our study suggests that smoking behavior-related SNPs are likely to play a role in melanoma development and the potential public health importance of polymorphisms in the CHRNA5-A3-B4 gene cluster. Further larger studies are warranted to validate the findings.
多项研究报告称，吸烟与黑色素瘤风险呈负相关。本研究进一步检验了纳入遗传因素是否会为评估吸烟与黑色素瘤风险之间关联的潜在机制提供另一层面的依据。我们使用2298例黑色素瘤病例和6654例对照，研究了从全基因组关联研究（GWAS）中选取的与吸烟行为相关的单核苷酸多态性（SNP）与黑色素瘤风险之间的关联。在16个SNP中，有3个（15q25.1区域的rs16969968[A]、rs1051730[A]和rs2036534[C]）在男性中与黑色素瘤风险的关联达到显著水平（0.01 <= P值 <= 0.02；0.85 <= 比值比（OR） <= 1.20）。在健康专业人员随访研究（HPFS）中，基于吸烟行为风险等位基因数量的遗传评分与黑色素瘤风险之间存在关联，P趋势 = 0.005。进一步分析发现，这3个SNP（rs16969968[A]、rs1051730[A]和rs2036534[C]）与每日吸烟量（CPD）显著相关，P值分别为0.009、0.011和0.001。PDE1C基因中的SNP rs215605和BDNF基因中的SNP rs6265与吸烟状态在黑色素瘤风险上存在显著交互作用（交互作用P值分别为0.005和0.003）。我们的研究表明，与吸烟行为相关的SNP可能在黑色素瘤发展中起作用，以及CHRNA5 - A3 - B4基因簇多态性在公共卫生方面的潜在重要性。有必要进行进一步的大规模研究来验证这些发现。
