IL-12A和IL-12B基因多态性与江苏人群宫颈癌遗传易感性相关  

Associations between potentially functional polymorphisms in IL-12A and IL-12B and risk of cervical cancer in Jiangsu women

作　　者：陈小军[1] 钱年凤[1] 胡志斌[2] 沈洪兵[2] 韩素萍[1] 

机构地区：[1]南京医科大学第一附属医院妇产科,江苏南京210029 [2]南京医科大学肿瘤中心流行病与卫生统计教研室,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2009年第8期1146-1152,共7页Journal of Nanjing Medical University(Natural Sciences)

摘　　要：目的:探讨IL-12A和IL-12B基因多态性与江苏人群宫颈癌的遗传易感性的关系。方法:采用病例对照研究,对经组织学确诊的宫颈癌新发病例404例按年龄和城乡频数匹配正常对照404例,以聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对IL-12A基因的rs568408(3’UTRG>A)、rs2243115(5’UTRT>G)和IL12B基因的rs3212227(3’UTRA>C)进行多态性检测,比较不同基因型与宫颈癌发病风险的关系。结果:在调整年龄、城乡等因素后,携带IL-12A rs568408 GA/AA和IL-12B rs3212227 AC/CC突变基因型的个体发生宫颈癌的风险较携带IL-12A rs568408 GG和IL-12B rs3212227 AA野生基因型的个体分别增加了43%(调整OR=1.43,95% CI=1.06～1.93)和30%(调整OR=1.30,95%CI=0.97～1.75),并且该两位点之间存在基因-基因相乘交互作用(P=0.048),同时携带两个突变基因型的个体发生宫颈癌的风险增加了82%(调整OR=1.82,95% CI=1.28～2.57)。分层分析表明,两基因位点的联合作用在早期宫颈癌患者和多产的患者中更为显著。同时携带两个突变基因型并且活产数大于2的个体发生宫颈癌的危险增加6倍(调整OR=6.00,95% CI=2.86～12.56),并且存在显著的基因环境相乘交互作用(P=0.046)。结论:IL-12A rs568408和IL-12B rs3212227基因多态性位点可能单独或共同影响江苏人群宫颈癌发病风险,并且与个体的活产数有关。Objective：To investigate the association between the potentially functional polymorphisms in IL-12A and IL-12B and risk of cervical cancer. Methods：The case-control study was conducted in Jiangsu female population, including 404 cervical cancer cases and 404 cancer-free controls frequency-matched by age and residential areas. The genotype of the IL-12A rs568408, rs2243115 and IL-12B rs3212227 polymorphisms were determined by polymerase chain reaction restriction and fragment length polymorphism （PCR-RFLP） assays. Results：The IL-12A rs568408 GA/AA and IL-12B rs3212227 AC/CC variant genotypes were associated with a significantly increased risk of cervical cancer [ adjusted odds ratio （OR）=1.43,95% confidence interval（CI）=1.06-1.93 and adjusted OR=1.30,95% CI=0.97-1.75, respectively ], compared with their corresponding wild-type homozygotes. Moreover, a significant gene- gene interaction of these two loci were evident in the risk of cervical cancer （P for multiplicative interaction=0.048） ; subjects carrying variant genotypes of both loci had a 1.82-fold （95% CI=1.28-2.57） increased risk of cervical cancer. In the stratified analyses,the combined genetic effect was more pronounced in patients with early-stage tumors and those with more parities. Subjects carrying rs568408 AG/AA and rs3212227 AC/CC genotypes and having more than 2 parities showed a 6.00-fold （95% CI=2.86-12.56） elevated cervical cancer risk （P for multiplicative interaction=0.046）. Conclusion：These findings indicate that IL-12A rs568408 and IL-12B rs3212227 may individually and jointly contribute to the risk of cervical cancer, and may modify cervical cancer risk associated with parity.

关 键 词：IL-12 单核苷酸多态性 宫颈癌 分子流行病学 

分 类 号：R737.33[医药卫生—肿瘤]