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Meta-Analysis
. 2010 May 15;116(10):2416-28.
doi: 10.1002/cncr.24994.

Does MC1R genotype convey information about melanoma risk beyond risk phenotypes?

Peter A Kanetsky  1 , Saarene Panossian, David E Elder, DuPont Guerry, Michael E Ming, Lynn Schuchter, Timothy R Rebbeck
Affiliations
Meta-Analysis

Does MC1R genotype convey information about melanoma risk beyond risk phenotypes?

Peter A Kanetsky et al. Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1. Meta-analysis of associations of MC1R genotype and melanoma stratified by hair color (a, b), eye color (c,d), skin color (e, f), skin type (g, h), sun exposure (i, j), and nevus count (k, l)
Study-specific odds ratios (OR, squares) and 95% confidence intervals (CI, horizontal lines) and pooled odds ratios and 95% CI (diamonds) for carriage of MC1R variants are shown; for all comparisons, the referent group is individuals who do not carry any MC1R variant. Number of cases and total number of individuals within each stratum are indicated.
Figure 1
Figure 1. Meta-analysis of associations of MC1R genotype and melanoma stratified by hair color (a, b), eye color (c,d), skin color (e, f), skin type (g, h), sun exposure (i, j), and nevus count (k, l)
Study-specific odds ratios (OR, squares) and 95% confidence intervals (CI, horizontal lines) and pooled odds ratios and 95% CI (diamonds) for carriage of MC1R variants are shown; for all comparisons, the referent group is individuals who do not carry any MC1R variant. Number of cases and total number of individuals within each stratum are indicated.
Figure 1
Figure 1. Meta-analysis of associations of MC1R genotype and melanoma stratified by hair color (a, b), eye color (c,d), skin color (e, f), skin type (g, h), sun exposure (i, j), and nevus count (k, l)
Study-specific odds ratios (OR, squares) and 95% confidence intervals (CI, horizontal lines) and pooled odds ratios and 95% CI (diamonds) for carriage of MC1R variants are shown; for all comparisons, the referent group is individuals who do not carry any MC1R variant. Number of cases and total number of individuals within each stratum are indicated.
Figure 1
Figure 1. Meta-analysis of associations of MC1R genotype and melanoma stratified by hair color (a, b), eye color (c,d), skin color (e, f), skin type (g, h), sun exposure (i, j), and nevus count (k, l)
Study-specific odds ratios (OR, squares) and 95% confidence intervals (CI, horizontal lines) and pooled odds ratios and 95% CI (diamonds) for carriage of MC1R variants are shown; for all comparisons, the referent group is individuals who do not carry any MC1R variant. Number of cases and total number of individuals within each stratum are indicated.
Figure 1
Figure 1. Meta-analysis of associations of MC1R genotype and melanoma stratified by hair color (a, b), eye color (c,d), skin color (e, f), skin type (g, h), sun exposure (i, j), and nevus count (k, l)
Study-specific odds ratios (OR, squares) and 95% confidence intervals (CI, horizontal lines) and pooled odds ratios and 95% CI (diamonds) for carriage of MC1R variants are shown; for all comparisons, the referent group is individuals who do not carry any MC1R variant. Number of cases and total number of individuals within each stratum are indicated.
Figure 1
Figure 1. Meta-analysis of associations of MC1R genotype and melanoma stratified by hair color (a, b), eye color (c,d), skin color (e, f), skin type (g, h), sun exposure (i, j), and nevus count (k, l)
Study-specific odds ratios (OR, squares) and 95% confidence intervals (CI, horizontal lines) and pooled odds ratios and 95% CI (diamonds) for carriage of MC1R variants are shown; for all comparisons, the referent group is individuals who do not carry any MC1R variant. Number of cases and total number of individuals within each stratum are indicated.
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