Affiliations of authors: M. T. Landi, M. A. Tucker, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; A. Baccarelli, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, and Epidemiology Research Center, University of Milan, Italy; A. Pesatori, Epidemiology Research Center, University of Milan; M. Hedayati, L. Grossman, Department of Biochemistry, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD; R. E. Tarone, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute.
Correspondence to: Maria Teresa Landi, M.D., Ph.D., Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd. EPS 7114, Bethesda, MD 208927236 (e-mail: landim{at}mail.nih.gov).
We thank Pedeux et al. for their interesting comments. It is true that the host cell reactivation assay is based on lymphocytes that are not exposed to UV. Indeed, this fact is a strength of the assay (1) because it allows measurement of constitutional DNA repair capacity (DRC) that is independent of secondary damage that might be caused by UV exposure to the host cells. UV may induce DRC (2) and tanning (3) in cultured skin cells, but the effects of sunlight exposure in vivo are not known (and are not amenable to measurement in an epidemiologic study). In our article we referenced a small investigation (4) conducted in skin biopsy specimens taken immediately after UV irradiation from melanoma case patients and control subjects. Similar to our results, no overall association between DRC and melanoma risk was found. In our study, recreational sun exposure was marginally associated with DRC among case patients (Table 2 in the original manuscript) but did not differ statistically significantly between case patients and control subjects. In addition, there was no statistical interaction between DRC and lifetime recreational sun exposure in their association with melanoma risk. For these reasons, we did not control for sun exposure in the analyses reported. However, all the results were practically identical when the models were adjusted for lifetime recreational sun exposure (between 11:00 AM and 3:00 PM), for occupational sun exposure, or for recent (up to 5 months before the study) sun exposure. Thus, although we cannot directly measure the effects of UV-induced photoprotective responses, we think it is unlikely that our results are distorted by differential UV-dependent induction of DRC between case patients and control subjects.
As for the second hypothesis raised in the letter, a slight decrease in DRC with age in healthy subjects and an interaction between DRC and age in their association with skin cancer risk have been described (5, 6). Our casecontrol study was frequency matched by decade of age, and all analyses reported in the manuscript were adjusted for age. We have reproduced the analysis presented for apoptosis and report the distribution of DRC by casecontrol status and by age (Fig. 1). There is no evidence of effect modification by age. Similarly, there was no difference in DRC when we used the median age (46 years) as a cutoff value for the analysis. Although the authors' results on apoptosis are intriguing, the possibility of false-positive findings is increased by post hoc subgroup analyses; thus, such analyses must be interpreted with caution. In this regard, the apoptosis results for ages 4059 years would be required to fully interpret the hypothesized effect modification by age for apoptosis.
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REFERENCES
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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.
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4
Xu G, Snellman E, Bykov VJ, Jansen CT, Hemminki K. Cutaneous melanoma patients have normal repair kinetics of ultraviolet-induced DNA repair in skin in situ.J Invest Dermatol 2000;114:62831.
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Goukassian D, Gad F, Yaar M, Eller MS, Nehal US, Gilchrest BA. Mechanisms and implications of the age-associated decrease in DNA repair capacity. FASEB J 2000;14:132534.
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