Re: Markers of DNA Repair and Susceptibility to Cancer in Humans: an Epidemiologic Review

We have summarized all of the published epidemiologic studies on DNA repair in human cancer through 1998 that addressed the association of cancer susceptibility with a putative defect in DNA repair capacity

K. Hemminki

2002

Scholarcy highlights

  • DNA repair is a system of defenses designed to protect the integrity of the genome
  • We have summarized what we believe to be all of the relevant human epidemiologic studies that have addressed the role of a defect in DNA repair capacity in the development of cancer
  • Many of the assays are measuring a response of phytohemagglutinin-stimulated lymphocytes to a mutagenic agent and, as stated in the “Discussion” section under the subheading entitled “Confounding,” we do not know the extent to which the results may depend on responses to unmeasured endogenous sensitizing or protective agents rather than on intrinsic DNA repair capacity
  • It must be stressed that the results shown in the tables represent the state of the art for measurements of DNA repair in human epidemiology studies
  • While associations with cancer risk have been observed in the assays described, the specificity of these assays as measures of DNA repair and, more importantly, as repair of carcinogenic or even mutagenic lesions in DNA is as yet undetermined
  • PARP susceptibility genotype: AfricanAmericans, 2.3; MexicanAmericans, 3.2; interaction effects in MexicanAmericans were 17.1; mutagen sensitivity was significantly associated with increased odds ratios above 2 for all ethnic groups
  • A firm conclusion cannot be drawn, there are a few aspects that are worth noting: The vast majority of studies show a difference between cancer case subjects and control subjects; this observation is compatible with a chromosomal instability due to cancer itself, it is notable that impaired mutagen sensitivity was observed in healthy relatives of cancer case subjects; there are a variety of functional tests that only indirectly address DNA repair and that show high variability in their expression; and the issue of confounding is almost totally unexplored, many of the observed associations are too strong to be attributable to confounders
  • Cloos et al found that N-acetylcysteine supplementation did not modify DNA repair capacity, as measured by bleomycin-induced mutagen sensitivity

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