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Sun exposure, vitamin D receptor polymorphisms FokI and BsmI and risk of multiple primary melanoma
Cancer Epidemiol. 2011 May 23.
Mandelcorn-Monson R, Marrett L, Kricker A, Armstrong BK, Orlow I, Goumas C, Paine S, Rosso S, Thomas N, Millikan RC, Pole JD, Cotignola J, Rosen C, Kanetsky PA, Lee-Taylor J, Begg CB, Berwick M.
Division of Dermatology, 1448 Laurence Avenue East, Suite 302, University of Toronto, Toronto, Canada M5N1T5.
Background: Sunlight exposure increases risk of melanoma. Sunlight also potentiates cutaneous synthesis of vitamin D, which can inhibit melanoma cell growth and promote apoptosis. Vitamin D effects are mediated through the vitamin D receptor (VDR).
We hypothesized that genetic variation in VDR affects the relationship of sun exposure to risk of a further melanoma in people who have already had one.
Methods: We investigated the interaction between VDR polymorphisms and sun exposure in a population-based multinational study comparing 1138 patients with a multiple (second or subsequent) primary melanoma (cases) to 2151 patients with a first primary melanoma (controls); essentially a case-control study of melanoma in a population of melanoma survivors. Sun exposure was assessed using a questionnaire and interview, and was shown to be associated with multiple primary melanoma. VDR was genotyped at the FokI and BsmI loci and the main effects of variants at these loci and their interactions with sun exposure were analyzed.
Results: Only the BsmI variant was associated with multiple primary melanoma (OR=1.27, 95% CI 0.99-1.62 for the homozygous variant genotype). Joint effects analyses showed highest ORs in the high exposure, homozygous variant BsmI genotype category for each sun exposure variable. Stratified analyses showed somewhat higher ORs for the homozygous BsmI variant genotype in people with high sun exposure than with low sun exposure. P values for interaction, however, were high.
Conclusion: These results suggest that risk of multiple primary melanoma is increased in people who have the BsmI variant of VDR.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Zeljic, Katarina; Kandolf-Sekulovic, Lidija; Supic, Gordana; Pejovic, Janko; Novakovic, Marijan; Mijuskovic, Zeljko; Magic, Zvonko
Previous studies have reported that vitamin D receptor (VDR) gene polymorphisms are associated with the occurrence of various cancers, including melanoma. The aim of the current study was to investigate the association of VDR gene polymorphisms with melanoma risk, clinicopathological characteristics, and vitamin D levels. The study group included 117 patients (84 patients with superficial spreading melanoma and 33 patients with nodular melanoma). The control group included 122 sex-matched and age-matched healthy-blood donors of the same ethnicity. VDR gene polymorphisms FokI, EcoRV, TaqI, and ApaI were genotyped by real-time PCR. In 60 patients, the total 25-hydroxyvitamin D levels were evaluated in serum samples by direct chemiluminescence. Associations among parameters were considered to be significant if the P value was less than 0.05.
Significant differences in the frequencies of VDR genotypes were observed between cases and the control group for
FokI and TaqI polymorphisms (P<0.0001; P=0.005, respectively). Heterozygous Ff as well as mutant FF genotypes of the FokI polymorphism were associated with increased melanoma risk compared with the wild-type form [odds ratio (OR)=3.035, P=0.003; OR=9.276, P<0.0001, respectively]. A significantly increased melanoma risk was observed for the heterozygous Tt (OR=2.302, P=0.011) and the mutated variant tt (OR=3.697, P=0.003) of the TaqI polymorphism in comparison with the wild-type genotype.
None of the polymorphisms studied was associated with clinicopathological characteristics and vitamin D serum level.
Our results suggest that FokI and TaqI polymorphisms in the VDR gene may be considered as potential biomarkers for melanoma susceptibility.
Low vitamin D levels in melanoma patients indicate the need for vitamin D supplementation.
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