Polymorphisms of the Interleukin 6 gene contribute to cervical cancer susceptibility in Eastern Chinese women

Hum Genet. 2013 Mar;132(3):301-12. doi: 10.1007/s00439-012-1245-4. Epub 2012 Nov 20.

Abstract

Interleukin 6 (IL6) encodes a cytokine protein, which functions in inflammation, maintains immune homeostasis and plays important roles in cervical carcinogenesis. Single nucleotide polymorphisms (SNPs) in IL6 that cause variations in host immune response may contribute to cervical cancer risk. In this two-stage case-control study with a total of 1,584 cervical cancer cases and 1,768 cancer-free female controls, we investigated associations between two IL6 SNPs and cervical cancer risk in Eastern Chinese women. In both Study 1 and Study 2, we found a significant association of the IL6-rs2069837 SNP with an increased risk of cervical cancer as well as in their combined data (OR 1.27 and 1.19, 95% CI 1.08-1.49 and 1.04-1.36, P = 0.004 and 0.014 for dominant and additive genetic models, respectively). Furthermore, rs2069837 variant AG/GG carriers showed significantly higher levels of IL6 protein than did rs2069837 AA carriers in the target tissues. Using multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses, we observed some evidence of interactions of the IL6 rs2069837 SNP with age at primiparity and menopausal status in cervical cancer risk. We concluded that the IL6-rs2069837 SNP may be a marker for susceptibility to cervical cancer in Eastern Chinese women by a possible mechanism of altering the IL6 protein expression. Although lacked information on human papillomavirus (HPV) infection, our study also suggested possible interactions between IL6 genotypes and age at primiparity or menopausal status in cervical carcinogenesis. However, larger, independent studies with detailed HPV infection data are warranted to validate our findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Asian Continental Ancestry Group / genetics*
  • Asian Continental Ancestry Group / statistics & numerical data
  • Carcinoma / genetics
  • Carcinoma / immunology
  • Case-Control Studies
  • China / epidemiology
  • Computer Simulation
  • Confounding Factors, Epidemiologic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Interleukin-6 / genetics*
  • Interleukin-6 / immunology*
  • Logistic Models
  • Menopause
  • Middle Aged
  • Neoplasm Staging
  • Parity
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / pathology

Substances

  • IL6 protein, human
  • Interleukin-6