Original paper

Cancer Causes & Control

, Volume 21, Issue 12, pp 2137-2147

First online:

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

  • Anne KrickerAffiliated withSydney School of Public Health, The University of Sydney Email author 
  • , Bruce K. ArmstrongAffiliated withSydney School of Public Health, The University of Sydney
  • , Chris GoumasAffiliated withSydney School of Public Health, The University of Sydney
  • , Peter KanetskyAffiliated withUniversity of Pennsylvania
  • , Richard P. GallagherAffiliated withBritish Columbia Cancer Agency
  • , Colin B. BeggAffiliated withMemorial Sloan-Kettering Cancer Center
  • , Robert C. MillikanAffiliated withDepartment of Epidemiology, School of Public Health, University of North Carolina
  • , Terence DwyerAffiliated withRoyal Children’s Hospital
  • , Stefano RossoAffiliated withPiedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont
    • , Loraine D. MarrettAffiliated withCancercare Ontario
    • , Nancy E. ThomasAffiliated withDepartment of Dermatology, Lineberger Comprehensive Cancer Center, University of North Carolina
    • , Marianne BerwickAffiliated withUniversity of New Mexico
    • , GEM Study Group

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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.

Keywords

Melanoma MC1R polymorphism Sun exposure Pigmentary phenotype