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Interactions of IL-12A and IL-12B Polymorphisms on the Risk of Cervical Cancer in Chinese Women

Authors' Affiliations: ¹ Laboratory of Reproductive Medicine, Nanjing Medical University, ² Department of Epidemiology and Biostatistics, Cancer Center of Nanjing Medical University, ³ Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, and ⁴ Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing, China; ⁵ Tumor Hospital of Nantong City, Nantong, China; and ⁶ Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Zhibin Hu or Hongbing Shen, Department of Epidemiology and Biostatistics, Cancer Center of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China. Phone: 86-25-868-62756; Fax: 86-25-865-27613; E-mail: zhibin_hu{at}njmu.edu.cn or hbshen{at}njmu.edu.cn.

Purpose: 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.

Experimental Design: 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).

Conclusion: 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.