MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study.
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.
Kricker
Anne
A
Sydney School of Public Health, The University of Sydney, Sydney, NSW 2006, Australia. anne.kricker@sydney.edu.au
Armstrong
Bruce K
BK
Goumas
Chris
C
Kanetsky
Peter
P
Gallagher
Richard P
RP
Begg
Colin B
CB
Millikan
Robert C
RC
Dwyer
Terence
T
Rosso
Stefano
S
Marrett
Loraine D
LD
Thomas
Nancy E
NE
Berwick
Marianne
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000209:etiology* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008545:Melanoma / Q000209:etiology* / Q000235:genetics; D008875:Middle Aged; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D013472:Sunlight / Q000009:adverse effects*; D055815:Young Adult
D044102:Receptor, Melanocortin, Type 1