Common variants of DNA repair genes and malignant melanoma

Eur J Cancer. 2008 Jan;44(1):110-4. doi: 10.1016/j.ejca.2007.10.006. Epub 2007 Nov 19.


In the current study, we evaluated the possible associations of seven common variants of the DNA repair and cell cycle control genes BRCA2 and CHEK2 with malignant melanoma (MM). We genotyped 630 unselected MM patients and over 3700 controls (newborns, age- and sex-matched healthy adults with negative cancer family histories, and the adults selected at random by family doctors) for the prevalence of three common variants of the BRCA2 (T1915M, N991D and N372H) and four common variants of the CHEK2 (1100delC, VS2+1G --> A, I157T and del5395). Our study strongly suggests that the common variant of the BRCA2 gene -- the N991D variant is associated with malignant melanoma risk (OR=1.8, p=0.002 after Bonferroni correction). Patients homozygote for the N991D variant were present in 0.32% of cases and only 0.13% of controls. The other variants studied were not over-represented among MM patients when compared to the general population. In conclusion, we report an increased melanoma risk among carriers of the N991D change of the BRCA2 and no association of the CHEK2 changes with malignant melanoma.

Publication types

  • Multicenter Study

MeSH terms

  • Case-Control Studies
  • Checkpoint Kinase 2
  • DNA Repair / genetics*
  • Female
  • Genes, BRCA2*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Melanoma / genetics*
  • Middle Aged
  • Mutation / genetics
  • Pedigree
  • Polymerase Chain Reaction / methods
  • Protein Serine-Threonine Kinases / genetics*
  • Skin Neoplasms / genetics*


  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases