Association of Vitamin D Receptor Polymorphisms With the Risk of Nonmelanoma Skin Cancer in Adults

Abstract

IMPORTANCE Protective effects of UV-B radiation against nonmelanoma skin cancer (NMSC) are exerted via signaling mechanisms involving the vitamin D receptor (VDR). Recent studies have examined single-nucleotide polymorphisms (SNPs) in the VDR, resulting in contradictory findings as to whether these polymorphisms increase a person's risk for NMSC.OBJECTIVE To examine whether the polymorphisms in the VDR gene are associated with the development of NMSC and the demographic characteristics of the participants. DESIGN, SETTING, AND PARTICIPANTSThis case-control study recruited 100 individuals who received a diagnosis of and were being treated for basal cell carcinoma or squamous cell carcinoma (cases) and 100 individuals who were receiving treatment of a condition other than skin cancer (controls) at the dermatology clinics at the Kirklin Clinic of the University of Alabama at Birmingham Hospital between January 1, 2012, and December 31, 2014. All participants completed a questionnaire that solicited information on skin, hair, and eye color; skin cancer family history; and sun exposure history, such as tanning ability and number of severe sunburns experienced throughout life. Blood samples for DNA genotyping were collected from all participants. MAIN OUTCOMES AND MEASURESPolymorphisms in the VDR gene (ApaI, BsmI, and TaqI) were assessed to determine the association of polymorphisms with NMSC development and demographic characteristics. χ 2 Analysis was used to determine whether genotype frequencies deviated significantly from Hardy-Weinberg equilibrium. Logistic regression was used to calculate odds ratios (ORs) and associated 95% CIs for the identification of factors associated with NMSC diagnosis. A model was created to predict NMSC diagnoses using known risk factors and, potentially, VDR SNPs. RESULTS A total of 97 cases and 100 controls were included. Of the 97 cases, 68 (70%) were men and 29 (30%) were women, with a mean (SD) age of 70 (11) years. Of the 100 controls, 46 (46%) were men and 54 (54%) were women, with a mean (SD) age of 63 (9) years. All participants self-identified as non-Hispanic white. A model including age, sex, and skin color was created to most effectively predict the incidence of skin cancer. Risk factors that significantly increased the odds of an NMSC diagnosis were light skin color (OR, 5.79 [95% CI, 2.79-11.99]), greater number of severe sunburns (OR, 2.59 [95% CI, 1.31-5.10]), light eye color (OR, 2.47 [95% CI, 1.30-4.67]), and less of an ability to tan (OR, 2.35 [95% CI,). The risk factors of family history of NMSC (OR, 1.66 [95% CI, 0.90-3.07]) and light hair color (OR, 1.17 [95% CI, 0.51-2.71]) did not reach statistical significance. Participants with the BsmI SNP were twice as likely to develop NMSC than participants with no mutation (OR, 2.04 [95% CI, 1.02-4.08]; P = .045). CONCLUSIONS AND RELEVANCEThe results of this study are especially useful in the early treatment and prevention of NMSC with chemopreventive agents (for those with the BsmI SNP). A screening for the BsmI SNP may e...

Vitamin D and the Risk of Non-Melanoma Skin Cancer: A Systematic Literature Review and Meta-Analysis on Behalf of the Italian Melanoma Intergroup

“…Five papers reported on the association between any of five polymorphisms of the VDR gene ( Apa1 , Bsm1 , Cdx2 , Fok1 , and Taq1 ) and NMSC risk [ 13 , 29 , 30 , 31 , 32 ]. The studies were conducted in the USA (n = 2) and Europe (n = 3) ( Table 4 ).…”

The Role of Classical and Novel Forms of Vitamin D in the Pathogenesis and Progression of Nonmelanoma Skin Cancers

“…Moreover, VDR activity can be influenced by single-nucleotide polymorphisms (SNPs) [254]. This plays, for example, a role in the etiology of nonmelanoma skin cancers (NMSC) and melanoma [38,54,104,111,117]. Interestingly, CYP11A1-derived D3 hydroxyderivatives without a hydroxyl group at C1α display a subset of the activities possessed by 1,25(OH) 2 D3 (see above) and lack calcemic activity, acting as biased agonists on the VDR [197,207].…”

“…In a Polish population, the TT genotype of FokI VDR polymorphism was correlated with greater than tenfold higher risk of BCC development [111]. Burns et al found that the BsmI b or TaqI t genotypes of VDR were more frequent in NMSC patients, suggesting that individuals with these genotypes are more likely to develop skin cancer [38]. A very recent nested case control study and meta-analysis showed that patients with rs2228570, rs927650, and rs1544410 recessive genotypes were characterized by a lower risk of SCC development, while rs7975232 and rs739837 recessive genotypes were related to decreased BCC risk [107].…”

Vitamin D and Vitamin D Analogs as Adjuncts to Field Therapy Treatments for Actinic Keratoses: Current Research and Future Approaches

“…It is interesting that vitamin D is both produced in the skin and exerts its effects on the skin via VDR. VDR transcription rate depends on the availability of VDR agonists and antagonists and can also be influenced by singlenucleotide polymorphisms, which play a role in the etiology of NMSC [28][29][30][31][32][33]. In the skin, VDR expression can fluctuate based on the pathology of skin conditions.…”