IRF4 Polymorphism Is Associated with Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients: A Pigment-Independent Phenomenon

Asgari, Maryam M.; Toland, Amanda E.; Arron, Sarah T.

doi:10.1016/j.jid.2016.07.038

Cited by 13 publications

(18 citation statements)

References 15 publications

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“…A recent study by Asgari et al . examined SNPs previously implicated in SCC in nontransplant populations in both candidate gene studies and GWAS . Eight SNPs were analysed for associations with post‐transplant SCC.…”

Section: Omics Of Post‐transplant Cancermentioning

confidence: 99%

“…Candidate SNP studies have implicated a number of genes including GSTM1 [77] and MTHFR [78] in post-transplant NMSC but very few studies have examined skin cancer in transplant populations at a genomewide scale. A recent study by Asgari et al [79] examined SNPs previously implicated in SCC in nontransplant populations in both candidate gene studies and GWAS [80,81]. Eight SNPs were analysed for associations with posttransplant SCC.…”

Section: Omics Of Post-transplant Cancermentioning

confidence: 99%

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Using omics to explore complications of kidney transplantation

2017

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SUMMARYThe importance of genetic and biochemical variation in renal transplant outcomes has been clear since the discovery of the HLA in the 1950s. Since that time, there have been huge advancements in both transplantation and omics. In recent years, there has seen an increased number of genome-, proteome-and transcriptome-wide studies in the field of transplantation moving away from the earlier candidate gene/protein approaches. These areas have the potential to lead to the development of personalized treatment depending on individual molecular risk profiles. Here, we discuss recent progress and the current literature surrounding omics and renal transplant complications.

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Section: Omics Of Post‐transplant Cancermentioning

confidence: 99%

Section: Omics Of Post-transplant Cancermentioning

confidence: 99%

Using omics to explore complications of kidney transplantation

2017

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“…Finally, post‐transplant medications have also been associated with skin cancer risk, including overall intensity and duration of immunosuppression, as well as specific medications with carcinogenic or photosensitization effects. Genetic risk predictors for cSCC have been identified for the general population; these are currently under investigation for the transplant population …”

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confidence: 99%

Risk prediction tools for keratinocyte carcinoma after solid organ transplantation: a review of the literature

et al. 2017

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Long-term iatrogenic immunosuppression increases the risk of cutaneous malignancies in organ transplant recipients (OTRs), particularly the keratinocyte cancers basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC). cSCC is the most common malignancy in OTRs, with the risk increased to over 65-fold in transplanted patients relative to the general population. There have been very few risk prediction tools developed for accurate determination of the risk of developing keratinocyte cancers in the OTR population. This review summarizes the prediction tools developed to date, and outlines future directions for developing more accurate prediction models that are clinically useful for the transplant physician and dermatologist.

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“…Two recent GWASs for cSCC found multiple variants, including novel variants not previously linked to pigmentation or skin cancer, at the OCA2 / HERC2 locus that were associated with an increase in the risk of cSCC independently of their estimated impacts on pigmentation . One previous study looked at the OCA2 / HERC2 variants rs916977 and rs12916300 in OTRs and did not see an association with cSCC risk; however, it was underpowered to identify an effect of the same magnitude observed in the GWAS . Importantly, several models to predict cSCC in OTRs incorporate eye colour (blue, hazel or green) as a risk variable …”

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confidence: 99%

“…Only a few studies have specifically evaluated OCA2 / HERC2 locus variants for cSCC risk, and these have shown association between multiple OCA2 / HERC2 locus variants and cSCC risk . Based on the data from both mouse and human, we hypothesized that variants at the human equivalent of Skts1 , specifically those mapping to the OCA2 / HERC2 locus, would be associated with time to cSCC in OTRs, a population at elevated risk for cSCC.…”

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confidence: 99%

Variants at theOCA2/HERC2locus affect time to first cutaneous squamous cell carcinoma in solid organ transplant recipients collected using two different study designs

et al. 2017

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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 as well as risk of developing multiple types of skin cancer. Objectives The goal of this study was to evaluate OCA2/HERC2 locus variants for 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 organ transplant recipients ascertained from two centers (n=125 and 261) with an average of 13.1 years follow-up post-transplant. DNA was available for genotyping for all participants in addition to medical records and questionnaire data. The Ohio State University (OSU) study design was a case-control with prospective follow-up, and the University of California San Francisco (UCSF) study design 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 to individuals homozygous for the blue eye alleles [HR=0.34, p<0.001and HR=0.54, p=0.012, respectively]. Both variants were highly associated with eye color in 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 which may impact dermatologic screening recommendations for high-risk populations.

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IRF4 Polymorphism Is Associated with Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients: A Pigment-Independent Phenomenon

Cited by 13 publications

References 15 publications

Using omics to explore complications of kidney transplantation

Using omics to explore complications of kidney transplantation

Risk prediction tools for keratinocyte carcinoma after solid organ transplantation: a review of the literature

Variants at theOCA2/HERC2locus affect time to first cutaneous squamous cell carcinoma in solid organ transplant recipients collected using two different study designs

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