Human leucocyte antigen-G polymorphisms are associated with cervical squamous cell carcinoma risk in Taiwanese women

Eur J Cancer. 2014 Jan;50(2):469-74. doi: 10.1016/j.ejca.2013.10.018. Epub 2013 Nov 18.

Abstract

Background: The mere presence of human papillomavirus (HPV) is not enough for cervical cancer development and immunogenetic background may play an important role. Human leucocyte antigen (HLA)-G acts as a negative regulator of immune responses and its expression in tumour cells may enable them to avoid immune attack. We aim to study if polymorphisms in the HLA-G gene are associated with cervical cancer risk in Taiwanese women.

Methods: +1537 A/C, 14-bp deletion/insertion (Del/Ins), and +3142 G/C polymorphisms were genotyped in a hospital-based study of 317 women with cervical squamous cell carcinoma (CSCC) and 400 healthy control women frequency matched by age. The presence and genotypes of HPV in CSCC were determined.

Results: We found the +3142 C/C genotype and C allele were associated with increased risk for CSCC (adjusted odds ratio [OR]=1.78, P=0.004; adjusted OR=1.31, P=0.014, respectively). In subgroup analysis based on HPV type 16 positivity, significant associations with higher adjusted ORs were found in +3142 C/C genotype and C allele (adjusted OR=2.19, P=0.001; adjusted OR=1.48, P=0.003, respectively) and +1537 C/C genotype and C allele frequencies increased significantly (adjusted OR=2.88, P=0.004; adjusted OR=1.69, P=0.0005, respectively). Furthermore, the C-Del-C haplotype conferred increased risk of both CSCC and HPV-16 positive CSCC women (adjusted OR=1.41, P=0.009; adjusted OR=1.94, P=0.0001, respectively).

Conclusion: These findings suggest that HLA-G gene is involved in the susceptibility to CSCC.

Keywords: Cervical cancer; HLA-G; HPV; Immunity; Polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Asian People / genetics
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / ethnology
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • HLA-G Antigens / genetics*
  • Humans
  • INDEL Mutation
  • Middle Aged
  • Odds Ratio
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / ethnology
  • Polymorphism, Genetic*
  • Risk Factors
  • Taiwan
  • Uterine Cervical Neoplasms / complications
  • Uterine Cervical Neoplasms / ethnology
  • Uterine Cervical Neoplasms / genetics*

Substances

  • HLA-G Antigens