Sporadic colorectal cancer and individual susceptibility: a review of the association studies investigating the role of DNA repair genetic polymorphisms

Mutat Res. May-Jun 2007;635(2-3):118-145. doi: 10.1016/j.mrrev.2007.02.001. Epub 2007 Feb 28.


Mutations in one of the DNA repair genes are one of the most common reasons for cancer, and it may be assumed that the individual genetic background modulating the DNA repair capacity may affect the susceptibility to cancer. Numerous polymorphisms (mainly SNPs) have been identified for DNA repair genes, although their functional outcome and phenotypic effect is often unknown. The aim of the present review is to evaluate the studies investigating a possible influence of DNA repair polymorphisms in the risk of sporadic colorectal cancer and/or adenoma. Overall, no relevant common findings emerge among the studies, except for some statistically significant associations between polymorphisms in the XRCC1 and XPD genes, mainly for colorectal adenoma risk. Other individual associations remain to be confirmed. This inconclusive data may suggest that the modulation of cancer risk depends not only on a single gene/SNP, but also on a joint effect of multiple polymorphisms (or haplotypes) within different genes or pathways, in close interaction with environmental factors. The relevance of many low-penetrance genes in cancer susceptibility is supposed to be very subtle. Several reviewed association studies revealed weaknesses in their design. However, there has been a progressive improvement over the years in aspects such as simultaneous genotyping and combined analyses of different polymorphisms in larger numbers of patients and controls, as well as stratification of results by ethnicity, gender, and tumor localization. This gained experience shows that only carefully designed studies of a sufficient statistical power may resolve the relationships between polymorphisms and colorectal cancer risk.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Colorectal Neoplasms / genetics*
  • DNA Damage / genetics*
  • DNA Repair / genetics*
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Polymorphism, Genetic*