Genetic variants and risk of cervical cancer: epidemiological evidence, meta-analysis and research review

BJOG. 2014 May;121(6):664-74. doi: 10.1111/1471-0528.12638. Epub 2014 Feb 19.

Abstract

Background: More than 200 articles have been published in the past 20 years on associations between genetic variants and risk of cervical cancer but the results have generally been inconsistent.

Objective: To provide a synopsis of the current understanding of the genetic architecture of the risk of cervical cancer by conducting a systematic review and meta-analysis.

Search strategy: We conducted a systematic literature search by a two-stage strategy using PubMed and other databases on or before 31 March 2012.

Selection criteria: Cross-sectional, case-control or cohort studies about the relationship between genetic variants and cervical cancer were included.

Data collection and analysis: Study outcomes were presented as odds ratios (ORs) with a 95% confidence interval.We did the meta-analysis for genetic variants which had at least three data sources and for which the significant associations were assessed using the Venice criteria.

Main results: A total of 5605 publications were screened, of which 286 were eligible. Meta-analysis was conducted for 58 variants in 25 genes or loci. Fourteen variants in 11 genes or loci could increase the risk of cervical cancer and five variants in three genes or loci could decrease the risk. The epidemiological evidence of the association was graded as strong for four variants in CTLA4 and HLA DQB1, moderate for five variants in IL-1B, IL-10, XRCC3 and HLA DQA1, and weak for 10 variants.

Conclusions: Many genetic variants were associated with the risk of cervical cancer as supported by the epidemiological evidence in this meta-analysis.

Keywords: Epidemiological evidence; genetic variants; meta-analysis; uterine cervical neoplasms.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • CTLA-4 Antigen / genetics*
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / prevention & control*
  • Genetic Variation
  • HLA-DQ alpha-Chains / genetics
  • HLA-DQ beta-Chains / genetics*
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-1beta / genetics
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / prevention & control

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human
  • DNA-Binding Proteins
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • Interleukin-1beta
  • X-ray repair cross complementing protein 3
  • Interleukin-10