title: Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women.
abstract: OBJECTIVE
  Accumulative evidence suggests that interleukin-12 (IL-12) plays a central role in the Th1 responses and thus participates in the carcinogenesis of human papillomavirus-related cervical cancer. We hypothesized that potentially functional polymorphisms in IL12A and IL12B may individually and jointly contribute to cervical cancer risk.
  
  
  METHODS
  We genotyped IL12A rs568408 [3' untranslated region (UTR) G>A] and rs2243115 (5'UTR T>G) and IL12B rs3212227 (3'UTR A>C) in a hospital-based study of 404 cervical cancer cases and 404 cancer-free controls.
  
  
  RESULTS
  The IL12A rs568408 GA/AA and IL12B rs3212227 AC/CC variant genotypes were associated with a significantly increased risk of cervical cancer [adjusted odds ratio, 1.43; 95% confidence interval (CI), 1.06-1.93; and adjusted odds ratio, 1.30; 95% CI, 0.97-1.75, respectively], compared with their corresponding wild-type homozygotes. Moreover, a significant gene-gene interaction of these 2 loci were evident in the risk of cervical cancer, and 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 who had early-stage tumors or more parities. Subjects carrying rs568408 AG/AA and rs3212227 AC/CC genotypes and having >2 parities showed a 6.00-fold (95% CI, 2.86-12.56) elevated cervical cancer risk (P for multiplicative interaction = 0.046).
  
  
  CONCLUSIONS
  These findings suggest that IL12A rs568408 and IL12B rs3212227 may individually and jointly contribute to the risk of cervical cancer and may modify cervical cancer risk associated with parity, but these data need further validation.
authors.affiliation: Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Chen
authors.forename: Suping
authors.initials: S
authors.lastname: Han
authors.forename: Sumin
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Zhou
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Shi
authors.forename: Nianfeng
authors.initials: N
authors.lastname: Qian
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008875:Middle Aged; D010298:Parity; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012306:Risk; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: C508858:IL12A protein, human; C500879:IL12B protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40