MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study
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We investigated whether MC1R genotype modifies the effect of sun exposure on melanoma risk in 1,018 cases with multiple melanomas (MPM) and 1,875 controls with one melanoma (SPM). There was some suggestion that MC1R genotype modified the effect of beach and water activities on MPM risk: ORs were 1.94 (95% CI 1.40–2.70) for any activities for no R variants and 1.39 (95% CI 1.05–1.84) with R variants (R151C, R160W, D294H, and D84E) (p for interaction 0.08). MC1R modification of sun exposure effects appeared most evident for MPM of the head and neck: for early life ambient UV, the OR was 4.23 (95% CI 1.76–10.20) with no R and 1.04 (95% CI 0.40–2.68) with R (p for interaction = 0.01; p for three-way interaction = 0.01). Phenotype modified the effect of sun exposure and MPM in a similar manner. We conclude that MC1R and pigmentary phenotype may modify the effects of sun exposure on melanoma risk on more continuously sun-exposed skin. Possible explanations include that risk may saturate with higher sun sensitivity for melanomas on continuously sun-exposed sites but continue to increase as sun exposure increases with lower sun sensitivity, or that sun-sensitive people adapt their behavior by increasing sun protection when exposed.
KeywordsMelanoma MC1R polymorphism Sun exposure Pigmentary phenotype
The study was conducted by the GEM Study Group: Marianne Berwick (PI University of New Mexico), Memorial Sloan-Kettering Cancer Center: Colin B Begg (Co-PI), Irene Orlow (Co-Investigator), Klaus Busam (Dermatopathologist). Study centers included the following: The University of Sydney and Cancer Council New South Wales, Sydney, Australia: Bruce K Armstrong (PI), Anne Kricker (Co-PI); Menzies Centre for Population Health Research, University of Tasmania, Hobart, Australia: Terence Dwyer (PI, currently at the Murdoch Childrens Research Institute, Melbourne, Victoria), Paul Tucker (Dermatopathologist), Alison Venn (PI); British Columbia Cancer Agency, Vancouver, Canada: Richard P. Gallagher (PI); Cancer Care Ontario, Toronto, Canada: Loraine D. Marrett (PI), Elizabeth Theis (Co-Investigator), Lynn From (Dermatopathologist); Centro per la Prevenzione Oncologia Torino, Piemonte, Italy: Stefano Rosso (PI); Roberto Zanetti (Co-PI); University of California, Irvine: Hoda Anton-Culver (PI); University of Michigan, Ann Arbor: Stephen B. Gruber (PI); University of North Carolina, Chapel Hill: Robert C. Millikan (PI), Nancy Thomas (Co-Investigator); University of Pennsylvania: Timothy R. Rebbeck (PI), Peter Kanetsky (Co- Investigator). UV data consultants: Dr Julia Lee Taylor and Dr Sasha Madronich, National Center for Atmospheric Research, Boulder, Colorado.
National Cancer Institute (NCI) grants U01 CA83180 and R01 112524; NCI Preventive Oncology Academic Award grant K07 CA80700 (Peter Kanetsky); University of Sydney Medical Foundation Program grant (Bruce Armstrong); NCI grant CA098438 (Colin. Begg); Michael Smith Foundation for Health Research Infrastructure Award (Richard Gallagher); Lineberger Comprehensive Cancer Center Core grant P30 CA16086 (Robert Millikan).
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