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.

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.

• Authors: 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
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 177 Issue 4 Pg. 1066-1073 (Oct 2017) ISSN: 1365-2133 [Electronic] England
• PMID: 28456133 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2017 British Association of Dermatologists.

Chemical References

• Guanine Nucleotide Exchange Factors
• Membrane Transport Proteins
• OCA2 protein, human
• HERC2 protein, human
• Ubiquitin-Protein Ligases

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alleles
• Carcinoma, Squamous Cell (genetics)
• Child
• Cross-Sectional Studies
• Eye Color (genetics)
• Female
• Genotype
• Guanine Nucleotide Exchange Factors (genetics)
• Humans
• Male
• Membrane Transport Proteins (genetics)
• Middle Aged
• Organ Transplantation
• Postoperative Complications (genetics)
• Retrospective Studies
• Risk Factors
• Skin Neoplasms (genetics)
• Transplant Recipients
• Ubiquitin-Protein Ligases
• Young Adult