Association of Vitamin D Receptor Polymorphisms With the Risk of Nonmelanoma Skin Cancer in Adults | Cancer Screening, Prevention, Control | JAMA Dermatology | JAMA Network
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1.
Rogers  HW, Weinstock  MA, Harris  AR,  et al.  Incidence estimate of nonmelanoma skin cancer in the United States, 2006.  Arch Dermatol. 2010;146(3):283-287.PubMedGoogle ScholarCrossref
2.
American Cancer Society. Cancer facts & figures 2014. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2014.html. Published 2014. Accessed December 11, 2014.
3.
The Lewin Group; Society for Investigative Dermatology and the American Academy of Dermatology Association. The burden of skin diseases 2005. http://medicina.uach.cl/proyectos/piel_artificial/upload/bibliografia/Skin_Diseases_Burden_USA.pdf. Published 2005. September 20, 2015.
4.
American Cancer Society. Basal and squamous cell skin cancer risk factors. https://www.cancer.org/cancer/basal-and-squamous-cell-skin-cancer/causes-risks-prevention/risk-factors.html. Revised May 10, 2016. Accessed September 20, 2017.
5.
American Cancer Society. Cancer facts & figures 2012. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2012.html. Published 2012. Accessed September 20, 2015.
6.
Boukamp  P.  Non-melanoma skin cancer: what drives tumor development and progression?  Carcinogenesis. 2005;26(10):1657-1667.PubMedGoogle ScholarCrossref
7.
Freedman  DM, Dosemeci  M, McGlynn  K.  Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study.  Occup Environ Med. 2002;59(4):257-262.PubMedGoogle ScholarCrossref
8.
Garland  CF, Garland  FC, Gorham  ED,  et al.  The role of vitamin D in cancer prevention.  Am J Public Health. 2006;96(2):252-261.PubMedGoogle ScholarCrossref
9.
Moukayed  M, Grant  WB.  Molecular link between vitamin D and cancer prevention.  Nutrients. 2013;5(10):3993-4021.PubMedGoogle ScholarCrossref
10.
Bikle  DD.  Protective actions of vitamin D in UVB induced skin cancer.  Photochem Photobiol Sci. 2012;11(12):1808-1816.PubMedGoogle ScholarCrossref
11.
Denzer  N, Vogt  T, Reichrath  J.  Vitamin D receptor (VDR) polymorphisms and skin cancer: a systematic review.  Dermatoendocrinol. 2011;3(3):205-210.PubMedGoogle ScholarCrossref
12.
Hustmyer  FG, DeLuca  HF, Peacock  M.  ApaI, BsmI, EcoRV and TaqI polymorphisms at the human vitamin D receptor gene locus in Caucasians, blacks and Asians.  Hum Mol Genet. 1993;2(4):487.PubMedGoogle ScholarCrossref
13.
Faraco  JH, Morrison  NA, Baker  A, Shine  J, Frossard  PM.  ApaI dimorphism at the human vitamin D receptor gene locus.  Nucleic Acids Res. 1989;17(5):2150.PubMedGoogle ScholarCrossref
14.
Morrison  NA, Yeoman  R, Kelly  PJ, Eisman  JA.  Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin.  Proc Natl Acad Sci U S A. 1992;89(15):6665-6669.PubMedGoogle ScholarCrossref
15.
Jurutka  PW, Whitfield  GK, Hsieh  JC, Thompson  PD, Haussler  CA, Haussler  MR.  Molecular nature of the vitamin D receptor and its role in regulation of gene expression.  Rev Endocr Metab Disord. 2001;2(2):203-216.PubMedGoogle ScholarCrossref
16.
Han  J, Colditz  GA, Hunter  DJ.  Polymorphisms in the MTHFR and VDR genes and skin cancer risk.  Carcinogenesis. 2007;28(2):390-397.PubMedGoogle ScholarCrossref
17.
Lesiak  A, Norval  M, Wodz-Naskiewicz  K,  et al.  An enhanced risk of basal cell carcinoma is associated with particular polymorphisms in the VDR and MTHFR genes.  Exp Dermatol. 2011;20(10):800-804.PubMedGoogle ScholarCrossref
18.
Köstner  K, Denzer  N, Koreng  M,  et al.  Association of genetic variants of the vitamin D receptor (VDR) with cutaneous squamous cell carcinomas (SCC) and basal cell carcinomas (BCC): a pilot study in a German population.  Anticancer Res. 2012;32(1):327-333.PubMedGoogle Scholar
19.
Wei-Passanese  EX, Han  J, Lin  W, Li  T, Laden  F, Qureshi  AA.  Geographical variation in residence and risk of multiple nonmelanoma skin cancers in US women and men.  Photochem Photobiol. 2012;88(2):483-489.PubMedGoogle ScholarCrossref
20.
Lee  YH, Gyu Song  G.  Vitamin D receptor FokI, BsmI, TaqI, ApaI, and EcoRV polymorphisms and susceptibility to melanoma: a meta-analysis.  J BUON. 2015;20(1):235-243.PubMedGoogle Scholar
21.
Raimondi  S, Pasquali  E, Gnagnarella  P,  et al.  BsmI polymorphism of vitamin D receptor gene and cancer risk: a comprehensive meta-analysis.  Mutat Res. 2014;769:17-34.PubMedGoogle ScholarCrossref
22.
Zeljic  K, Kandolf-Sekulovic  L, Supic  G,  et al.  Melanoma risk is associated with vitamin D receptor gene polymorphisms.  Melanoma Res. 2014;24(3):273-279.PubMedGoogle ScholarCrossref
23.
Zhao  XZ, Yang  BH, Yu  GH, Liu  SZ, Yuan  ZY.  Polymorphisms in the vitamin D receptor (VDR) genes and skin cancer risk in European population: a meta-analysis.  Arch Dermatol Res. 2014;306(6):545-553.PubMedGoogle ScholarCrossref
24.
Gandini  S, Gnagnarella  P, Serrano  D, Pasquali  E, Raimondi  S.  Vitamin D receptor polymorphisms and cancer.  Adv Exp Med Biol. 2014;810:69-105.PubMedGoogle Scholar
Original Investigation
October 2017

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

Author Affiliations
  • 1Department of Dermatology, University of Alabama at Birmingham
  • 2Department of Epidemiology, University of Alabama at Birmingham
  • 3Genetic Counseling Program, University of Alabama at Birmingham
JAMA Dermatol. 2017;153(10):983-989. doi:10.1001/jamadermatol.2017.1976
Key Points

Question  Is there an association between vitamin D receptor single-nucleotide polymorphisms and the risk of nonmelanoma skin cancer?

Findings  This case-control study involving 100 case patients and 100 control patients proposed a model for predicting the incidence of skin cancer and found that individuals with the BsmI single-nucleotide polymorphism were twice as likely to develop nonmelanoma skin cancer than those with no mutation.

Meaning  A screening for the BsmI single-nucleotide polymorphism may emphasize the need for skin cancer prevention for individuals with this polymorphism.

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 Participants  This 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 Measures  Polymorphisms in the VDR gene (ApaI, BsmI, and TaqI) were assessed to determine the association of polymorphisms with NMSC development and demographic characteristics. χ2 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, 1.23-4.48]). 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 Relevance  The 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 emphasize the importance of sun protection and facilitate skin cancer prevention and, therefore, decrease the skin cancer burden.

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