Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin

Abstract

BackgroundHuman pigmentation is a polygenic quantitative trait with high heritability. In addition to genetic factors, it has been shown that pigmentation can be modulated by oestrogens and androgens via up- or down-regulation of melanin synthesis. Our aim was to identify possible sex differences in pigmentation phenotype as well as in melanoma association in a melanoma case-control population of Spanish origin.MethodsFive hundred and ninety-nine females (316 melanoma cases and 283 controls) and 458 males (234 melanoma cases and 224 controls) were analysed. We genotyped 363 polymorphisms (single nucleotide polymorphisms (SNPs)) from 65 pigmentation gene regions.ResultsWhen samples were stratified by sex, we observed more SNPs associated with dark pigmentation and good sun tolerance in females than in males (107 versus 75; P = 2.32 × 10−6), who were instead associated with light pigmentation and poor sun tolerance. Furthermore, six SNPs in TYR, SILV/CDK2, GPR143, and F2RL1 showed strong differences in melanoma risk by sex (P < 0.01).ConclusionsWe demonstrate that these genetic variants are important for pigmentation as well as for melanoma risk, and also provide suggestive evidence for potential differences in genetic effects by sex.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-016-0070-1) contains supplementary material, which is available to authorized users.

A double-blinded randomised controlled trial – do subcuticular non-absorbable skin sutures have a better aesthetic outcome than skin staples in large wound closures?

“…The reason may be the differing skin texture, in that male skin tends to have higher concentration of melanin and is more pliable than female skin. The differences allow better healing [12] (Table 2 (Tab. 2), Table 3 (Tab.…”

Genetic 3′UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight

“…Genotype‐related odds ratios (ORs), their corresponding 95% confidence intervals (CIs) and associated P ‐values were estimated. Association analyses with phenotypic traits were adjusted by sex, because sex‐differentiated allelic effects for pigmentation traits, sensitivity to sunlight and melanoma have been previously shown …”

The genetic basis of sunlight sensitivity and melanoma-risk pigmentation phenotypes: The role of sex-specific genetic effects, 3' untranslated regions and melanoma susceptibility genes

“…Replication of our findings in a larger study is therefore essential before drawing any firm conclusion. It is noted that adjusting analyses by sex has conferred strength to our results, excluding bias from the sexual disparity in pigmentation and melanoma incidence and outcome observed in previous studies (25,131,132,162,163). correlation between melanocytic naevus number, a main risk-prediction factor for melanoma incidence, and the propensity to burn, rather than tan, of light-skinned individuals (212).…”

“…Association analyses with phenotypic traits were adjusted by sex, since sex-differentiated allelic effects for pigmentation traits, sensitivity to sunlight and melanoma have been previously shown (132,162,163).…”

“…Females exhibit lower incidence, lower risk of metastases and significantly longer survival rates than males (130,131). Sex differences in pigmentation traits, tanning ability, and skin sensitivity to sunlight exposure may explain the sex disparity described in melanoma epidemiology (108,131,132). Additionally, individuals who are immunosuppressed, for example after an organ transplantation, are at higher risk of melanoma (133).…”