Variants at the OCA2/HERC2 locus affect time to first cutaneous squamous cell carcinoma in solid organ transplant recipients collected using two different study designs

被引：11

作者：

Wei, L. ^{[1
]}

Allain, D. C. ^{[2
]}

Bernhardt, M. N. ^{[2
]}

Gillespie, J. L. ^{[5
]}

Peters, S. B. ^{[3
]}

Iwenofu, O. H. ^{[4
]}

Nelson, H. H. ^{[6
,7
]}

Arron, S. T. ^{[8
]}

Toland, A. E. ^{[2
,5
]}

机构：

[1] Ohio State Univ, Wexner Med Ctr, Ctr Biostat, Dept Biomed Informat, Columbus, OH 43210 USA

[2] Ohio State Univ, Wexner Med Ctr, Div Human Genet, Dept Internal Med, Columbus, OH 43210 USA

[3] Ohio State Univ, Wexner Med Ctr, Dept Pathol, Div Dermatopathol, Columbus, OH 43210 USA

[4] Ohio State Univ, Wexner Med Ctr, Dept Pathol & Lab Med, Columbus, OH 43210 USA

[5] Ohio State Univ, Comprehens Canc Ctr, Dept Canc Biol & Genet, Columbus, OH 43210 USA

[6] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA

[7] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[8] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA

来源：

BRITISH JOURNAL OF DERMATOLOGY | 2017年 / 177卷 / 04期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; NONMELANOMA SKIN-CANCER; SINGLE-NUCLEOTIDE POLYMORPHISMS; SUSCEPTIBILITY LOCI; GENE POLYMORPHISMS; CANDIDATE GENE; UNITED-STATES; MODIFIER LOCI; EYE COLOR; PIGMENTATION;

D O I：

10.1111/bjd.15618

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Background Variants at the oculocutaneous albinism 2 (OCA2)/HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2) locus have been associated with pigmentation phenotypes and risk of developing several types of skin cancer. Objectives To evaluate OCA2/HERC2 locus variants for their impact on time to develop cutaneous squamous cell carcinoma (cSCC) in organ transplant recipients (OTRs) who are at elevated risk of developing cSCC. Methods Participants were solid OTRs ascertained from two centres (n = 125 and 261) with an average of 13 1 years of follow-up post-transplant. DNA was available for genotyping for all participants, in addition to medical records and questionnaire data. The Ohio State University study had a case-control design with prospective follow-up, and the University of California San Francisco study was a national cross-sectional survey with retrospective chart review. Results OCA2 variants rs12913832 and rs916977 were significantly associated with time to first cSCC post-transplant. OTRs homozygous for the brown-eye alleles of rs916977 (GG) and rs12913832 (AA) had significant delays of time to first cSCC post-transplant compared with individuals homozygous for the blue-eye alleles (hazard ratio 0.34, P < 0.001 and hazard ratio 0.54, P = 0.012, respectively). Both variants were highly associated with eye colour in the combined studies (P < 0.001). Conclusions This study is the first to show an association between OCA2/HERC2 variants and time to first cSCC post-transplant. This may impact dermatological screening recommendations for high-risk populations.

引用

页码：1066 / 1073

页数：8