Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2.
Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2.
复制标题
宫颈和外阴癌风险与白介素2中吸烟和遗传变异的关节作用有关。
DOI：
10.1158/1055-9965.epi-07-2753
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发表时间：
2008-07
期刊：
影响因子：
--
通讯作者：
Schwartz SM
中科院分区：
文献类型：
--
作者：
Hussain SK;Madeleine MM;Johnson LG;Du Q;Malkki M;Wilkerson HW;Farin FM;Carter JJ;Galloway DA;Daling JR;Petersdorf EW;Schwartz SM
吸烟是宫颈和外阴鳞状细胞癌（SCC）发展中人乳头瘤病毒（HPV）的一个既定辅助因素，并可能通过免疫抑制途径影响风险。白细胞介素2（IL 2）的遗传变异，在一些研究中与HPV靶向免疫抑制相关，可能会改变吸烟对HPV相关肛门生殖器癌风险的影响。我们进行了一项以人群为基础的仅病例研究，以测量吸烟和IL 2变化对宫颈和外阴SCC的倍增联合效应的偏离。在399例宫颈和486例外阴SCC病例中进行了4种IL 2 tagSNPs（rs 2069762、rs 2069763、rs 2069777和rs 2069778）的基因分型，这些病例接受了关于吸烟史的采访。与携带rs 2069762 TT基因型的病例相比，我们观察到吸烟和TG或GG基因型携带者在外阴SCC风险中的乘数显著偏离（交互作用比值比（IOR）=1.67，95%置信区间（CI）：1.16，2.41）。三种二倍体之一的携带者与吸烟一起与外阴癌风险的超倍增（TGCT/GGCC，IOR=2.09，95% CI：0.98，4.46）或亚倍增（TTCC/TGTC，IOR=0.37，95% CI：0.16，0.85或TGCT/TGCC，IOR=0.37，95% CI：0.15，0.87）联合效应相关。对于宫颈鳞状细胞癌，在rs 2069763变异等位基因（TT与GG或GT基因型）纯合子的吸烟者（IOR=1.87，95% CI：1.00，3.48）和TTCC/TTCC双倍型携带者（IOR=2.08，95% CI：1.01，4.30）中观察到与倍增性的偏离。这些结果表明，吸烟者宫颈和外阴SCC的风险是由IL 2的遗传变异修改。
Cigarette smoking is an established co-factor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was performed in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared to cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk (interaction odds ratio (IOR)=1.67, 95% confidence interval (CI): 1.16, 2.41). Carriership of one of three diplotypes together with cigarette smoking was associated with either a supra-multiplicative (TGCT/GGCC, IOR=2.09, 95% CI: 0.98, 4.46) or sub-multiplicative (TTCC/TGTC, IOR=0.37, 95% CI: 0.16, 0.85 or TGCT/TGCC, IOR=0.37, 95% CI: 0.15, 0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes) (IOR=1.87, 95% CI: 1.00, 3.48), and for carriership of the TTCC/TTCC diplotype, (IOR=2.08, 95% CI: 1.01, 4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2.