TP53 Polymorphisms and Colorectal Cancer Risk in Patients with Lynch Syndrome in Taiwan: A Retrospective Cohort Study

PLoS One. 2016 Dec 1;11(12):e0167354. doi: 10.1371/journal.pone.0167354. eCollection 2016.

Abstract

Background and aim: TP53 encodes p53, which has a crucial role in modulating genes that regulate defense against cancer development. This study investigated whether TP53 polymorphisms are associated with colorectal cancer (CRC) in patients with Lynch syndrome and whether TP53 interacts with lifestyle factors to modify CRC risk.

Methods: We identified 260 MLH1 and MSH2 germline mutation carriers from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association of TP53 polymorphisms with CRC development.

Results: The carriers of the variant C allele of rs1042522 were associated with a decreased CRC risk (GC genotype: HR = 0.35, 95% CI = 0.14-0.86; CC genotype: HR = 0.28, 95% CI = 0.13-0.57). In addition, the dominant model of rs1042522 was associated with a decreased CRC risk (HR = 0.32, 95% CI = 0.15-0.67). The CRC risk was decreased in carriers with the CT and TT genotypes of rs12947788 (HR = 0.20, 95% CI = 0.08-0.46 and HR = 0.25, 95% CI = 0.09-0.65, respectively). Moreover, the dominant model of rs12947788 was significantly associated with a decreased CRC risk (HR = 0.21, 95% CI = 0.09-0.46). A haplotype analysis indicated that compared with the most common GC haplotype, the CT haplotype was associated with a decreased CRC risk (HR = 0.26, 95% CI = 0.11-0.59). However, no significant interaction was observed between TP53 polymorphisms and lifestyle factors.

Conclusion: The study results revealed that the rs1042522 genotype with the C allele and the rs12947788 genotype with the T allele in TP53 were associated with a decreased CRC risk in patients with Lynch syndrome in Taiwan.

MeSH terms

  • Adult
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Germ-Line Mutation
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • MutL Protein Homolog 1 / genetics
  • MutS Homolog 2 Protein / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Retrospective Studies
  • Risk Factors
  • Taiwan
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • MLH1 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein

Grants and funding

This study was supported by the National Science Council, Executive Yuan, Taiwan (grant NSC 101-2314-B-038-057) and by the Ministry of Science and Technology, Taiwan (MOST 104-2314-B-038-009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.