Positivity for HLA DR1 is associated with basal cell carcinoma in renal transplant patients in southern Brazil

Carvalho, André Vicente Esteves de; Bonamigo, Renan Rangel; Silva, Cristina M. da; Pinto, Angela Caroline de Zorzi

doi:10.1111/j.1365-4632.2011.05282.x

Cited by 8 publications

(7 citation statements)

References 12 publications

(19 reference statements)

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“…Our incidence rate for posttransplant KC was 1,758 per 100,000 person-years for SCC and 1,648.5 per 100,000 person-years for BCC, which is comparable to previously published rates among organ transplant recipients (Garrett et al, 2017). Previous studies among RTRs have identified multiple HLA alleles that are associated with KC risk, including HLA-A*03, HLA-B*18, HLA-B*27, HLA-DRB1*01, HLA-DRB1*07, HLA-DRB1*15, and HLA-DQA1*01 (Bouwes Bavinck and Claas, 1994;Bouwes Bavinck et al, 1997;Cegielska et al, 2016;Czarnecki et al, 1992;de Carvalho et al, 2012;Glover et al, 1993;Qureshi, 1996;Yesantharao et al, 2017). In addition, recent genome-wide association studies reported several single nucleotide polymorphisms in the HLA class II gene region that are associated with KC risk (Asgari et al, 2016;Chahal et al, 2016a;Chahal et al, 2016b;Wang et al, 2018a), including HLA-DQA1, HLA-DQA2, and HLA-DQB1.…”

Section: Discussionsupporting

confidence: 85%

“…The mechanism of action is thought to be mediated by the impact of genetic changes in HLA impacting in the host defense system, such as losing the ability to present neoantigens through HLA loss, that may facilitate immune evasion (McGranahan et al, 2017). With respect to KC risk, previous studies have implicated different HLA genes and alleles, with the association varying with the population under investigation (immunosuppressed vs. immunocompetent or differing population structures) (Cegielska et al, 2016;Chahal et al, 2016a;Chahal et al, 2016b;de Carvalho et al, 2012;Wang et al, 2018b;Yesantharao et al, 2017). Recent genome-wide association studies have identified a locus that contains HLA class II genes, including HLA-DQA1 and HLA-DQB1, that are associated with increased KC risk (Asgari et al, 2016;Chahal et al, 2016a;Chahal et al, 2016b).…”

Section: Introductionmentioning

confidence: 99%

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Association between Human Leukocyte Antigen Type and Keratinocyte Carcinoma Risk in Renal Transplant Recipients

Kim

Wojciechowski

Pattanayak

et al. 2020

Journal of Investigative Dermatology

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Keratinocyte carcinoma (KC), defined as squamous cell carcinoma and basal cell carcinoma, is the most common malignancy among white, non-Hispanic renal transplant recipients. Although recent genome-wide association studies reported that class II HLA is associated with KC risk, epidemiologic data on HLA type and KC risk in renal transplant recipients is limited. Using an institutional cohort of white, non-Hispanic renal transplant recipients transplanted between 1993 and 2017, we examined the association between pretransplant molecular HLA types and KC risk. Posttransplant KCs were captured using the International Classification of Diseases codes and validated using pathology reports. Cox proportional hazards regression models were used to estimate hazard ratios of incident KC, squamous cell carcinoma, and basal cell carcinoma, adjusting for age, male sex, history of KC, Charlson comorbidity index, HLA mismatch, transplant type, year of transplant, and the type of immunosuppression. Among 617 subjects (mean age 53 years, 67% male), 10% developed posttransplant KC. Multivariable Cox regression analyses showed HLA-DRB1*13 was associated with KC risk (hazard ratio, 1.84; 95% confidence interval, 1.00e3.38) and squamous cell carcinoma risk (hazard ratio, 2.24; 95% confidence interval, 1.12e4.49), whereas HLA-DRB1*14 (hazard ratio, 2.81; 95% confidence interval, 1.14e6.91) was associated with basal cell carcinoma risk. Our findings suggest that a subset of renal transplant recipients with specific HLA polymorphisms may be at increased KC risk.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Association between Human Leukocyte Antigen Type and Keratinocyte Carcinoma Risk in Renal Transplant Recipients

Kim

Wojciechowski

Pattanayak

et al. 2020

Journal of Investigative Dermatology

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“…IGF2BP2 expression has been associated with liver cancer, liposarcoma, and endometrial adenocarcinomas, and with promotion of cell migration and metastasis (45,46). High expression of DR1 is associated with basal cell carcinoma in renal transplant patients (47). Another interesting potential miR-452 target gene, ARF4 (ADP-ribosylation factor 4), has been shown to promote breast cancer cell migration (48) and to inhibit apoptosis in glioblastoma (49).…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of the GABRE∼miR-452∼miR-224 Promoter in Prostate Cancer Predicts Biochemical Recurrence after Radical Prostatectomy

Kristensen

Haldrup

Strand

et al. 2014

Clinical Cancer Research

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Purpose: Available tools for prostate cancer diagnosis and prognosis are suboptimal and novel biomarkers are urgently needed. Here, we investigated the regulation and biomarker potential of the GABRE$miR-452$miR-224 genomic locus.Experimental Design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 nonmalignant and 281 prostate cancer tissue samples. GABRE$miR-452$miR-224 promoter methylation was determined by methylation-specific qPCR (MethyLight) in 35 nonmalignant, 293 prostate cancer [radical prostatectomy (RP) cohort 1] and 198 prostate cancer tissue samples (RP cohort 2). Diagnostic/prognostic biomarker potential of GABRE$miR-452$miR-224 methylation was evaluated by ROC, Kaplan-Meier, uni-and multivariate Cox regression analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and DU145 cells by viability, migration, and invasion assays and gene-set enrichment analysis (GSEA) of posttransfection transcriptional profiling data.Results: GABRE$miR-452$miR-224 was significantly downregulated in prostate cancer compared with nonmalignant prostate tissue and had highly cancer-specific aberrant promoter hypermethylation (AUC ¼ 0.98). Functional studies and GSEA suggested that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3 and DU145 cells by direct/indirect regulation of pathways related to the cell cycle and cellular adhesion and motility. Finally, in uni-and multivariate analyses, high GABRE$miR-452$miR-224 promoter methylation was significantly associated with biochemical recurrence in RP cohort 1, which was successfully validated in RP cohort 2.Conclusion: The GABRE$miR-452$miR-224 locus is downregulated and hypermethylated in prostate cancer and is a new promising epigenetic candidate biomarker for prostate cancer diagnosis and prognosis. Tumor-suppressive functions of the intronic miR-224 and miR-452 were demonstrated in two prostate cancer cell lines, suggesting that epigenetic silencing of GABRE$miR-452$miR-224 may be selected for in prostate cancer. Clin Cancer Res; 20(8); 2169-81. Ó2014 AACR.

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“…Multiple variants in HLA-DRB1 ( Ã 01, Ã 07) have shown increased risk for BCC while HLA-DRB1 Ã 04 was protective (82). HLA-DRB1 Ã 01 also correlated with increased BCC risk and early tumor development in renal transplant recipients (84). Among immunosuppressed patients, class-I antigens HLA-A03, HLA-A11, and HLA-B27 and class-II antigens, HLA-DRB1 Ã 07 and HLA-DQA1 Ã 01 correlated with increased risk cSCC (80).…”

Section: Germline Genetic Risk Factors and Risk Modelsmentioning

confidence: 99%

Keratinocyte Carcinomas: Current Concepts and Future Research Priorities

Nagarajan

Asgari

Green

et al. 2019

Clinical Cancer Research

108

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Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas, the most frequently diagnosed cancers in fair-skinned populations. Ultraviolet radiation (UVR) is the main driving carcinogen for these tumors, but immunosuppression, pigmentary factors, and aging are also risk factors. Scientific discoveries have improved the understanding of the role of human papillomaviruses (HPV) in cSCC as well as the skin microbiome and a compromised immune system in the development of both cSCC and BCC. Genomic analyses have uncovered genetic risk variants, high-risk susceptibility genes, and somatic events that underlie common pathways important in keratinocyte carcinoma tumorigenesis and tumor characteristics that have enabled development of prediction models for early identification of high-risk individuals. Advances in chemoprevention in high-risk individuals and progress in targeted and immune-based treatment approaches have the potential to decrease the morbidity and mortality associated with these tumors. As the incidence and prevalence of keratinocyte carcinoma continue to increase, strategies for prevention, including effective sun-protective behavior, educational interventions, and reduction of tanning bed access and usage, are essential. Gaps in our knowledge requiring additional research to reduce the high morbidity and costs associated with keratinocyte carcinoma include better understanding of factors leading to more aggressive tumors, the roles of microbiome and HPV infection, prediction of response to therapies including immune checkpoint blockade, and how to tailor both prevention and treatment to individual risk factors and needs.

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Positivity for HLA DR1 is associated with basal cell carcinoma in renal transplant patients in southern Brazil

Abstract: HLA DR1 appears to be associated with the development of BCC, as well as with the higher number of NMSC lesions in renal transplant patients. This study supports the trend to associate the DR1 allele with BCC and not with SCC.

Cited by 8 publications

References 12 publications

Association between Human Leukocyte Antigen Type and Keratinocyte Carcinoma Risk in Renal Transplant Recipients

Association between Human Leukocyte Antigen Type and Keratinocyte Carcinoma Risk in Renal Transplant Recipients

Hypermethylation of the GABRE∼miR-452∼miR-224 Promoter in Prostate Cancer Predicts Biochemical Recurrence after Radical Prostatectomy

Keratinocyte Carcinomas: Current Concepts and Future Research Priorities

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