CORRESPONDENCE

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

Marianne Berwick, Paolo Vineis

Affiliations of authors: M. Berwick, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; P. Vineis, Unit of Cancer Epidemiology, University of Torino, and Ospedale S. Giovanni Battista, Torino, Italy.

Correspondence to: Marianne Berwick, Ph.D., Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 588, New York, NY 10021 (e-mail: berwickm{at}mskcc.org).

We are pleased that Hemminki et al. have taken seriously the challenge in our recent review (1) to develop definitive molecular assays for DNA repair. Their conclusions echo ours: neither they nor we really know what the studies in lymphocytes measure. Clearly, their research publications in 1999 and 2000 will be valuable in developing the techniques for studying DNA repair.

We find it interesting that the two studies using kinetic tests on skin biopsies, which Hemminki et al. believe fulfill the criterion of biologic relevance, had positive and statistically significant results (although carried out in only a few subjects). Roth et al. (2) showed that melanoma subjects had lower DNA repair rates than control subjects (P < .001), and Alcalay et al. (3) showed that dimers in basal cell carcinoma subjects were eliminated less rapidly than in control subjects (P < .05).

The overall message that we derive from our analysis of the literature is that a considerable number of studies consistently found an association between biologic tests, whose significance is still obscure, and cancer at several sites. Looking at it this way, we agree with Hemminki and colleagues that further clarification of the biologic background is crucial. However, at this time, we think that focusing our attention on the design of the studies, reproducibility, sample size, and selection of control subjects was necessary to draw valid conclusions at the population level. The issue of biologic relevance of studies of DNA repair in lymphocytes is critical for epidemiologic studies where associations are derived from numerous subjects to define small reproducible alterations that may be important. Most of the work Hemminki et al. cite has been conducted in very small groups and has not yet been reproduced.

In sum, the issues raised by Hemminki et al. are critical for the appropriate assessment of DNA repair. We hope that other eminent scientists will join their efforts to develop appropriate assays for DNA repair.

REFERENCES

1 Berwick M, Vineis P. Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 2000;92:874–97.[Abstract/Free Full Text]

2 Roth M, Muller H, Boyle JM. Immunochemical determination of an initial step in thymine dimer excision repair in xeroderma pigmentosum variant fibroblasts and biopsy material from the normal population and patients with basal cell carcinoma and melanoma. Carcinogenesis 1987;8:1301–7.[Abstract]

3 Alcalay J, Freeman SE, Goldberg LH, Wolf JE. Excision repair of pyrimidine dimers induced by simulated solar radiation in the skin of patients with basal cell carcinoma. J Invest Dermatol 1990;95:506–9.[Abstract]



             
Copyright © 2000 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement