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Multicenter Study
. 2010 Dec;21(12):2137-47.
doi: 10.1007/s10552-010-9633-3. Epub 2010 Aug 19.

MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study

Anne Kricker  1 , Bruce K Armstrong, Chris Goumas, Peter Kanetsky, Richard P Gallagher, Colin B Begg, Robert C Millikan, Terence Dwyer, Stefano Rosso, Loraine D Marrett, Nancy E Thomas, Marianne Berwick; GEM Study Group
Affiliations
Multicenter Study

MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study

Anne Kricker et al. Cancer Causes Control. 2010 Dec.

Abstract

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.

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Figures

Figure 1
Figure 1
Risk of MPM on head and neck and other body sites: ORs for quartiles of average annual lifetime ambient UV (a,b) and average early life UV (c,d), and ORs for beach and water activities (none, tertiles of hours of average annual lifetime activities) (e,f) by MC1R genotype (no R, any R) in analyses adjusted for age, sex, age * sex, center, ancestry, pigment score; and ORs for beach and water activities (none, tertiles of hours of average annual lifetime activities) by pigmentary phenotype (sun resistent, sun sensitive) (g,h) in analyses adjusted for age, sex, age * sex, center, ancestry.
Figure 1
Figure 1
Risk of MPM on head and neck and other body sites: ORs for quartiles of average annual lifetime ambient UV (a,b) and average early life UV (c,d), and ORs for beach and water activities (none, tertiles of hours of average annual lifetime activities) (e,f) by MC1R genotype (no R, any R) in analyses adjusted for age, sex, age * sex, center, ancestry, pigment score; and ORs for beach and water activities (none, tertiles of hours of average annual lifetime activities) by pigmentary phenotype (sun resistent, sun sensitive) (g,h) in analyses adjusted for age, sex, age * sex, center, ancestry.
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