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

L. Wei, D. C. Allain, M. N. Bernhardt, J. L. Gillespie, S. B. Peters, O. H. Iwenofu, H. H. Nelson, S. T. Arron, A. E. Toland

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1066-1073
Number of pages8
JournalBritish Journal of Dermatology
Volume177
Issue number4
DOIs
StatePublished - Oct 2017

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health (R03 CA173788, P30 CA016058), the American Cancer Society (RSG-07-083-01-MGO) and the Ohio State University Comprehensive Cancer Center. The funders had no role in this study.

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