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Does MC1R genotype convey information about melanoma risk beyond risk phenotypes?
Author(s) -
Kanetsky Peter A.,
Panossian Saarene,
Elder David E.,
Guerry DuPont,
Ming Michael E.,
Schuchter Lynn,
Rebbeck Timothy R.
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24994
Subject(s) - medicine , odds ratio , melanoma , confidence interval , population , absolute risk reduction , relative risk , risk factor , genotype , eye color , demography , dermatology , genetics , environmental health , biology , cancer research , sociology , gene
BACKGROUND: A study was carried out to describe associations of MC1R variants and melanoma in a US population and to investigate whether genetic risk is modified by pigmentation characteristics and sun exposure measures. METHODS: Melanoma patients (n = 960) and controls (n = 396) self‐reported phenotypic characteristics and sun exposure via structured questionnaire and underwent a skin examination. Logistic regression was used to estimate associations of high‐ and low‐risk MC1R variants and melanoma, overall and within phenotypic and sun exposure strata. A meta‐analysis of results from published studies was undertaken. RESULTS: Carriage of 2 low‐risk or any high‐risk MC1R variants was associated with increased risk of melanoma (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.0‐2.8; and OR, 2.2; 95% CI, 1.5‐3.0, respectively). However, risk was stronger in or limited to individuals with protective phenotypes and limited sun exposure, such as those who tanned well after repeated sun exposure (OR, 2.4; 95% CI, 1.6‐3.6), had dark hair (OR, 2.4; 95% CI, 1.5‐3.6), or had dark eyes (OR, 3.2; 95% CI, 1.8‐5.9). We noted this same pattern of increased melanoma risk among persons who did not freckle, tanned after exposure to first strong summer sun, reported little or average recreational or occupational sun exposure, or reported no sun burning events. Meta‐analysis of published literature supported these findings. CONCLUSIONS: These data indicate that MC1R genotypes provide information about melanoma risk in those individuals who would not be identified as high risk based on their phenotypes or exposures alone. Cancer 2010. © 2010 American Cancer Society.