Affiliation of authors: R. Pedeux, M. Boniol, J.-F. Doré, Institut National de la Santé et de la Recherche Médicale, Unité 453, Lyon, France; P. Autier, Centre de Recherche Public de la Santé, Luxemburg, Luxemburg.
Present address and correspondence to: Rémy Pedeux, Ph.D., Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Bldg. 37, Rm. 2C26, Bethesda, MD 20892 (e-mail: pedeuxr{at}mail.nih.gov).
Landi et al. (1) recently reported in the Journal that DNA repair capacity (DRC) may modify the risk of melanoma in the presence of other strong risk factors, i.e., low tanning ability and/or presence of dysplastic nevi. This study provides the first report that low DRC may be associated with an increased risk for melanoma. Intriguingly, in this study, low DRC does not appear to be a risk factor for melanoma in the absence of other strong risk factors. However, it is established that deficiency in DNA repair mechanisms or higher mutagen sensitivity, as assessed by the induction of chromatid breaks, may play an important role in the development of melanoma (2, 3).
The absence of association between DRC and melanoma risk observed in the study by Landi et al. may be caused by a lack of sensitivity in the host cell reactivation assay. This assay measures DRC in lymphocytes that have not been exposed to the genotoxic stimulus (UV radiation). Indeed, UV-induced DNA damage triggers the induction of photoprotective responses, such as an increased DRC (4).
Alternatively, in the population selected by Landi et al., this absence of association may result from an age effect among case patients and control subjects or from differences in the distribution of individual DRC values between case patients and control subjects.
Inherited susceptibility factors are likely to be more manifest at an earlier age (5). When we analyzed data from a cutaneous melanomas registry for the region of Burgundy, France, we found that host susceptibility factors, such as eye color, which is classically associated with melanoma risk, actually appeared to be risk factors for the occurrence of melanoma before 50 years of age (6). Furthermore, to explore the relationship between inherited susceptibility to UV radiation and the risk of melanoma, we measured the apoptosis triggered in peripheral blood lymphocytes by a low dose of UVB radiation and considered the following two age groups of patients with cutaneous melanoma of the SSM (superficial spreading melanoma) type and of healthy control subjects: 1839 years old and 6069 years old. We observed that UVB induced more apoptosis in lymphocytes from patients with melanoma than in lymphocytes from control subjects (P<.001). This difference is highly statistically significant in the younger group, but there is no difference in the older group (Fig. 1, unpublished results).
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REFERENCES
1
Landi MT, Baccarelli A, Tarone RE, Pesatori A, Tucker MA, Hedayati M, et al. DNA repair, dysplastic nevi, and sunlight sensitivity in the development of cutaneous malignant melanoma. J Natl Cancer Inst 2002;94:94101.
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4
Eller MS, Maeda T, Magnoni C, Atwal D, Gilchrest BA. Enhancement of DNA repair in human skin cells by thymidine dinucleotides: evidence for a p53-mediated mammalian SOS response. Proc Natl Acad Sci U S A 1997;94:1262732.
5
Wei Q, Cheng L, Amos CI, Wang LE, Guo Z, Hong WK, et al. Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J Natl Cancer Inst 2000;92:176472.
6 Boniol M, Sallin J, Dore JF. Time trends of cutaneous melanoma in Queensland, Australia and Central Europe. Cancer 2002;94:19023.[Medline]
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