Risk Of Basal Cell Carcinoma Research Articles

Reduced risk of skin cancer and internal malignancies in vitiligo patients: a retrospective population-based cohort study in Taiwan

The relationship between cancer and vitiligo has been explored but with inconsistent results. To examine the long-term cancer risk in vitiligo patients, we conducted a retrospective nationwide cohort study. From the National Health Insurance Research Database of Taiwan, a total of 13,824 vitiligo patients were identified and matched with 55,296 reference subjects without vitiligo by age, gender, and propensity score estimated by major comorbidities from 1997 to 2013. Demographic characteristics and comorbidities were compared between these two groups. Incidence rate ratios and hazard ratios (HRs) were calculated to examine cancer risks. The 16-year incidence rates of overall cancers were 621.06 (566.56–675.55) and 726.99 (697.24–756.74) per 100,000 person-years in the vitiligo and reference groups. Patients with vitiligo showed a significantly decreased risk of overall cancers [adjusted HR, 0.85; 95% confidence interval (CI), 0.77 to 0.93, p < 0.001] compared with reference subjects without vitiligo after adjusting for age, sex, comorbidities, and treatments. The risks of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were significantly reduced (adjusted HR 0.21, 95% CI 0.11–0.38, p < 0.001), as well as internal malignancies (adjusted HR 0.89, 95% CI 0.81–0.99, p = 0.026). The results were consistent across different subgroups of patients, including male gender, ages more than 40 years, and those receiving long-term systemic disease-modifying antirheumatic drugs and phototherapies. Information related to phenotype, disease duration, vitiligo lesion sites, family history of vitiligo or cancer, occupation, and personal lifestyle was not included in the database. Vitiligo is associated with reduced risks of BCC and SCC, as well as internal malignancies.

High-Frequency Ultrasound and Shear Wave Elastography in Quantitative Differential Diagnosis of High-Risk and Low-Risk Basal Cell Carcinomas.

The purpose of this study was to investigate the value of high-frequency ultrasound and shear wave elastography (SWE) in quantitative differential diagnosis of high-risk and low-risk basal cell carcinomas (BCCs). A total of 52 BCCs confirmed by surgical pathology were studied. Taking pathologic subtypes as reference, all the cases were classified as high-risk BCCs or low-risk BCCs. High-frequency ultrasound parameters and SWE parameters recorded preoperatively were retrospectively analyzed. The differences of two groups were compared. There were 12 high-risk BCCs and 40 low-risk BCCs. The maximum infiltration depth (MID) and average Young's modulus (Eave ) of high-risk BCCs were 5.76± 2.56 mm and 31.61 ± 12.36 kPa, whereas of low-risk BCCs were 4.29± 1.77 mm and 20.04 ± 4.74 kPa, respectively, P< .05. The area under the receiver operator characteristic curve of MID and Eave were 0.714 and 0.811, P> .05. Taking 5.5 mm of MID and 24.45 kPa of Eave as the threshold for the diagnosis of high-risk BCCs, the sensitivity, specificity, and accuracy were 58.3%, 82.5%, 76.9% and 75.0%, 82.5%, 80.8%, P> .05. The MID and Eave of the lesion can be used to determine the recurrence risk of BCCs and provide a reference for the development of individualized treatment plans.

PTPN14 Mutations and Cervical Cancer.

It was recently shown that rare germline loss-of-function variants in the tyrosine-protein phosphatase non-receptor type 14 (PTPN14) gene conferred substantial risk of basal cell carcinoma (BCC). A follow-up investigation of 24 cancers and three benign tumor types showed that PTPN14 loss-of-function variants were associated with high risk of cervical cancer and early age at diagnosis. We used the Cancer Genome Atlas (TCGA) to further evaluate the PTPN14 - cervical cancer association. We analyzed the Genomic Data Commons (GDC) TCGA Cervical Cancer (CESC) data set. We used cBioPortal for Cancer Genomics to access data in TCGA. cBioPortal provides visualization, analysis and download options for large-scale cancer genomic data sets. We also accessed TCGA data with the University of California Santa Cruz (UCSC) Xena Browser. UCSC Xena allows users to explore functional genomic data sets for assessing correlations between genomic and/or phenotypic variables. Ten patients with PTPN14 mutations had significantly better survival than 266 patients without PTPN14 mutations (p=0.05 log rank test). In the Human Protein Atlas, low expression of PTPN14 in 85 TCGA cervical cancer specimens was associated with better survival than high expression in 206 cervical cancer specimens. In general, factors that affect the risk of a cancer have the same effect on prognosis. For example, history of allergy reduces risk of malignant brain tumors and improves prognosis. However, this relationship is not the case for PTPN14. We conclude that in TCGA cervical cancer specimens, PTPN14 mutation is a favorable prognostic factor. However, germline variants of PTPN14 confer a worse prognosis. Further studies of the specific mutations would be worthwhile.

Lifetime Ambient UV Radiation Exposure and Risk of Basal Cell Carcinoma by Anatomic Site in a Nationwide U.S. Cohort, 1983–2005

Cutaneous basal cell carcinoma (BCC) has long been associated with UV radiation (UVR) exposure, but data are limited on risks by anatomic site. We followed 63,912 cancer-free White U.S. radiologic technologists from cohort entry (1983-1989/1994-1998) to exit (date first BCC via 2003-2005 questionnaire). We estimated associations between cumulative ambient UVR and relative/absolute risks of self-reported BCC by anatomic location via Poisson models. For incident first primary BCC in 2,124 subjects (mean follow-up, 16.9 years) log[excess relative risks] (ERR) of BCC per unit cumulative ambient UVR = 1.27/MJ cm-2 [95% confidence interval (CI): 0.86-1.68; P trend < 0.001] did not vary by anatomic site (P = 0.153). However, excess absolute risks of BCC per unit cumulative ambient UVR were large for the head/neck = 5.46/MJ cm-2/104 person-year (95% CI: 2.92-7.36; P trend < 0.001), smaller for the trunk (2.56; 95% CI: 1.26-3.33; P trend = 0.003), with lesser increases elsewhere. There were lower relative risks, but higher absolute risks, for those with Gaelic ancestry (P < 0.001), also higher absolute risks among those with fair complexion, but relative and absolute risks were not generally modified by other constitutional, lifestyle or medical factors for any anatomic sites. Excess absolute and relative risk was concentrated 5-15 years before time of follow-up. BCC relative and absolute risk rose with increasing cumulative ambient UVR exposure, with absolute risk highest for the head/neck, to a lesser extent in the trunk. These associations should be evaluated in other White and other racial/ethnic populations along with assessment of possible modification by time outdoors, protective, and behavioral factors.

Increased cutaneous squamous cell carcinoma risk with hydrochlorothiazide use: is there a safe alternative?

Linked Article: Schneider et al. Br J Dermatol 2021; 185:343–352.

Abstract 844: Immune-related diseases and risk of skin cancer

Abstract Introduction: The immune system plays an important role in skin cancer development, as evidenced by elevated rates in organ transplant recipients. However, there are limited studies on the association between immune-related diseases and skin cancer. This study prospectively evaluates the relationship between immune-related diseases and risks of melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) using two cohorts of women and men: the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Methods: In the NHS and HPFS, participants completed biennial questionnaires that gathered information on lifestyle factors and medical history. In our study, the NHS data is comprised of 83,824 participants over a 26-year period (1986-2012), representing 1,738,926 person years. The HPFS data includes 48,277 participants over a 26-year period (1986-2012), representing 874,315 person years. Cox proportional hazard models were applied to estimate the associations between immune-related diseases (ulcerative colitis/Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypothyroidism, hyperthyroidism, and vitiligo) and skin cancer risk, both individually and as one composite variable. Multivariate models were adjusted for age and other skin cancer risk factors (body mass index, smoking status, alcohol consumption, hair color, number of blistering sunburns, nevi count, sunburn reaction, family history of melanoma and cumulative UV exposure level). Due to the small number and lower skin cancer risk in the nonwhite population, the analysis was limited to white participants. Exclusion criteria were participants who had melanoma, SCC, BCC, or other cancers at baseline. Results: During the follow-up period, 558 melanoma, 1,696 SCC, and 17,145 BCC incident cases were documented in the NHS and 589 melanoma, 1,388 SCC, and 9,962 BCC cases in the HPFS. When assessing individual diseases, there was a significantly increased risk for SCC and BCC among male participants with ulcerative colitis/Crohn's disease; relative risks (RR) were 1.69 (1.06, 2.67) and 1.38 (1.15, 1.66) respectively. Male participants with multiple sclerosis were also at a significantly increased risk of BCC; RR was 1.78 (1.17, 2.72) In female participants, participants with hypothyroidism and hyperthyroidism were at significantly decreased risk for BCC; RR were 0.88 (0.78, 0.99) and 0.81 (0.68, 0.96) respectively. There were no significant associations between diagnosis of skin cancer and immune-related diseases when evaluating them as one composite variable. Conclusions: Risk of skin malignancy in patients with immune-related diseases is disease dependent. There is an increased risk of SCC/BCC and BCC in male patients with ulcerative colitis/Crohn's disease and multiple sclerosis, respectively. Citation Format: Erica M. Lin, Rachel Lim, Tricia Li, Martin Weinstock, Abrar Qureshi, Eunyoung Cho. Immune-related diseases and risk of skin cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 844.

Common Genetic Polymorphisms Contribute to the Association between Non-Melanoma Skin Cancer and Chronic Lymphocytic Leukemia

Introduction: Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with numerous traits and diseases. The analysis of shared genetic associations between diseases can help explain previously found epidemiological associations and provide better insight into disease etiology. Epidemiological studies have demonstrated a consistent positive association between chronic lymphocytic leukemia (CLL) and non-melanoma skin cancers (NMSC); however, the reasons for this association are not well understood. We explored the hypothesis that shared genetic risk factors between CLL and NMSC could contribute to the epidemiological association observed between these diseases.Methods: We identified established loci associated with CLL or NMSC with p<5x10-8 based on published results. Single nucleotide polymorphisms (SNPs) were considered independent if they were ≥500 kb apart and had r2<0.05. We examined the association between NMSC loci and CLL risk in a pooled GWAS of CLL including 3,100 cases and 7,667 controls of European ancestry. In parallel, we investigated the association between CLL loci and NMSC risk in a study of 4,242 basal cell carcinoma (BCC) cases and 12,802 controls and also 825 squamous cell carcinoma (SCC) cases and 11,518 controls. Weighted genetic risk scores (wGRS) were constructed separately for each disease. For each SNP, the odds ratios (OR) for the association with NMSC or CLL was extracted from existing literature. In the wGRS, the number of risk alleles was multiplied by the log-OR of that SNP as reported in the literature. We estimated the OR and 95% confidence interval (95% CI) for the associations with individual SNPs and with the wGRS for both CLL and NMSC using logistic regression, adjusting for age, sex, and principal components to account for population substructure.Results: Six of the established genetic loci for CLL and NMSC overlapped such that at least SNPs associated with CLL and NMSC were within a 1 Mb: 2q33.1, 3q28, 5p15, 6p21, 6p25 and 9q21.Of the reported NMSC loci, 4 index SNPs were nominally associated with CLL risk after adjustment for multiple testing (PFDR-adjusted≤0.05): rs12203592 and rs12210050 at 6p25 (IRF4/EXOC2), rs78378222 at 17p13.1 (TP53), and rs191177147 at 3q28 (LPP). The most significant associations were at 6p25.3 region in the IRF4/EXOC2 locus: rs12203592 (OR: 1.41, 95% CI: 1.29-1.54, P=7.34 x 10-14) and rs12210050 (OR=1.23, 95% CI: 1.12-1.35, P=1.97 x 10-5). Using the wGRS from SCC SNPs, we found a pattern of increasing risk of CLL with increasing quartile, reaching statistical significance for quartile 4 vs. quartile 1 (OR=1.26, 95% CI: 1.14-1.39, P=0.001). After excluding the IRF4 polymorphism rs12203592, the association between the wGRS and CLL was no longer significant (OR=1.02, 95% CI: 0.90-1.45, P=0.81).Of the reported CLL SNPs, five were associated with NMSC risk after adjustment for multiple testing (PFDR-adjusted≤0.05): rs9815073 at 3q28 (LPP), rs3769825 at 2q33 (CASP10/CASP8), rs17246404 at 7q31 (POT1), rs4368253 at 18q21 (PMAIP1) and rs872071 at 6p25 (IRF4/EXOC2). The wGRS based on the CLL SNPs was associated with BCC risk (P=0.004) but not with SCC risk (P=0.12), possibly due to a lack of statistical power. Of note, after exclusion of the IRF4 polymorphism, the association between the wGRS and BCC remained statistically significant (P=0.02).Conclusion: We report here a novel and statistically significant association between the genetic burden for risk of NMSC and of CLL. Finally, we uncovered that polymorphisms in the Interferon Regulatory Factor 4 (IRF4) gene appear to contribute to the association between CLL and NMSC. IRF4, also known as multiple myeloma oncogene-1 (MUM1), is a transcriptional regulator expressed in lymphocytes and in melanocytes. Further studies are needed to understand the common biological mechanisms that lead to this association. Overall, these findings highlight the pleiotropic effect of genes in the pathogeneses of these cancers and suggest that they have a partially shared genetic etiology. DisclosuresSmedby:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding. Shanafelt:Genentech, Celgene, Pharamacyclics, Jansen, GlaxoSmithKline, AbbVie, Hospira, and Cephalon: Research Funding. Cerhan:Janssen: Other: Scientific Advisory Board (REMICADELYM4001); Janssen: Other: Multiple Myeloma Registry Steering.

Use of hydrochlorothiazide and risk of skin cancer in a large nested case-control study in Spain.

Hydrochlorothiazide (HCTZ) use has been linked to skin cancer in northern European countries. We assessed the association between HCTZ exposure and risk of malignant melanoma (MM) and keratinocyte carcinoma (KC) in a European Mediterranean population. Two parallel nested case-control studies were conducted in Spain using two electronic primary healthcare databases, each one providing data on both exposure and outcomes: SIDIAP and BIFAP. Cancer cases were matched to 10 controls by age and gender through risk-set sampling. The ORs and 95% CI for MM and KC associated with previous HCTZ use were estimated using conditional logistic regression. In BIFAP, KC cases were further identified as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). In adjusted analyses, both ever and cumulative high (≥50,000 mg) use of HCTZ were associated with an increased risk of KC. The risk estimates for high use were 1.30 (1.26-1.34) in SIDIAP and 1.20 (1.12-1.30) in BIFAP, with a lower risk for BCC (1.11 [1.02-1.21]) than for SCC (1.71 [1.45-2.02]). A dose-response relationship was observed between cumulative doses of HCTZ and KC risk. Inconsistent results were found for high use of HCTZ and risk of MM: 1.25 (1.09-1.43) in SIDIAP and 0.85 (0.64-1.13) in BIFAP. In this European Mediterranean population, a high cumulative use of HCTZ was related to an increased risk of KC with a clear dose-response pattern.

Polyunsaturated Fatty Acid Levels and the Risk of Keratinocyte Cancer: A Mendelian Randomization Analysis.

Keratinocyte cancer is the commonest cancer, imposing a high economic burden on the health care system. Observational studies have shown mixed associations between polyunsaturated fatty acids (PUFA) and keratinocyte cancer, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We explored whether genetically predicted PUFA levels are associated with BCC and SCC risks. We conducted a two-sample Mendelian randomization study using PUFA level genome-wide association studies (GWAS) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n > 8,000), and the meta-analysis GWASs from UKB, 23andMe, and Qskin for BCC (n = 651,138) and SCC (n = 635,331) risk. One SD increase in genetically predicted levels of linoleic acid [OR = 0.94, 95% confidence interval (CI) = 0.91-0.97, P = 1.4 × 10-4] and alpha-linolenic acid (OR = 0.91, 95% CI = 0.86-0.96, P = 5.1 × 10-4) was associated with a reduced BCC risk, while arachidonic acid (OR = 1.04, 95% CI = 1.02-1.06, P = 3.2 × 10-4) and eicosapentaenoic acid (OR = 1.10, 95% CI = 1.04-1.16, P = 1.5 × 10-3) were associated with an increased BCC risk. Higher genetically predicted levels of linoleic acid and alpha-linolenic acid were associated with a reduced BCC risk, but arachidonic acid and eicosapentaenoic acid were associated with a higher BCC risk. PUFA-related diet and supplementation could influence BCC etiology.

Polygenic Risk Scores Stratify Keratinocyte Cancer Risk among Solid Organ Transplant Recipients with Chronic Immunosuppression in a High Ultraviolet Radiation Environment

Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high UVR environments. We assessed whether polygenic risk scores can improve the prediction of BCC and SCC risks and multiplicity over and above the traditional risk factors in SOTRs in a high UV setting. We built polygenic risk scores for BCC (n= 594,881) and SCC (n= 581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Sun and Health Study cohort (n > 6,300), and applied them in SOTRs in the skin tumor in allograft recipients cohort from Queensland, Australia, a high UV environment. About half of the SOTRs with a high genetic risk developed BCC (absolute risk= 45.45%, 95% confidence interval= 33.14-58.19%) and SCC (absolute risk= 44.12%, 95% confidence interval= 32.08-56.68%). For both cancers, SOTRs in the top quintile were at >3-fold increased risk relative to those in the bottom quintile. The respective polygenic risk scores improved risk predictions by 2% for BCC (area under the curve= 0.77 vs. 0.75, P= 0.0691) and SCC (area under the curve= 0.84 vs. 0.82, P= 0.0260), over and above the established risk factors, and 19.03% (for BCC) and 18.10% (for SCC) of the SOTRs were reclassified in a high/medium/low risk scenario. The polygenic risk scores also added predictive accuracy for tumor multiplicity (BCC R2= 0.21 vs. 0.19, P= 3.2× 10-3; SCC R2= 0.30 vs. 0.27, P= 4.6× 10-4).

049 Personal history of rosacea and risk of basal cell carcinoma of the face: A regional analysis of Rhode Island

049 Personal history of rosacea and risk of basal cell carcinoma of the face: A regional analysis of Rhode Island

Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer.

Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases. We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus. These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.

Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland

Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed. To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC. A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression. Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96). This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies.

Loss-of-Function Variants in the Tumor-Suppressor Gene PTPN14 Confer Increased Cancer Risk.

The success of genome-wide association studies (GWAS) in identifying common, low-penetrance variant-cancer associations for the past decade is undisputed. However, discovering additional high-penetrance cancer mutations in unknown cancer predisposing genes requires detection of variant-cancer association of ultra-rare coding variants. Consequently, large-scale next-generation sequence data with associated phenotype information are needed. Here, we used genotype data on 166,281 Icelanders, of which, 49,708 were whole-genome sequenced and 408,595 individuals from the UK Biobank, of which, 41,147 were whole-exome sequenced, to test for association between loss-of-function burden in autosomal genes and basal cell carcinoma (BCC), the most common cancer in Caucasians. A total of 25,205 BCC cases and 683,058 controls were tested. Rare germline loss-of-function variants in PTPN14 conferred substantial risks of BCC (OR, 8.0; P = 1.9 × 10-12), with a quarter of carriers getting BCC before age 70 and over half in their lifetime. Furthermore, common variants at the PTPN14 locus were associated with BCC, suggesting PTPN14 as a new, high-impact BCC predisposition gene. A follow-up investigation of 24 cancers and three benign tumor types showed that PTPN14 loss-of-function variants are associated with high risk of cervical cancer (OR, 12.7, P = 1.6 × 10-4) and low age at diagnosis. Our findings, using power-increasing methods with high-quality rare variant genotypes, highlight future prospects for new discoveries on carcinogenesis. SIGNIFICANCE: This study identifies the tumor-suppressor gene PTPN14 as a high-impact BCC predisposition gene and indicates that inactivation of PTPN14 by germline sequence variants may also lead to increased risk of cervical cancer.

Risk of skin cancer by histological type in a cohort of workers chronically exposed to ionizing radiation.

The incidence risk of non-melanoma skin cancer (NMSC), in particular basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), was investigated in a cohort of workers of the Russian nuclear facility, the Mayak Production Association (PA), who had been occupationally exposed to low dose-rate ionizing radiation over prolonged periods. The study cohort included all workers who had been hired at the enterprise in1948-1982 and followed up to 31.12.2018 (22,377 individuals, 25% of females). The mean cumulative skin absorbed dose of external gamma-ray exposure was 0.50 ± 0.73Gy (the range of 0.00-8.84Gy); the mean cumulative skin absorbed dose of neutron exposure was 0.002 ± 0.004Gy (the range of 0.0000002-0.153Gy). Relative risk and excess relative risk per unit skin absorbed dose of external exposure (RR and ERR/Gy) were estimated using AMFIT module of EPICURE software. Over the entire follow-up period 295 (84.8%) BCC, 48 (13.8%) SCC and 5 (1.4%) skin appendage cell carcinomas (SACC) were registered among NMSC in members of the study cohort. A significant linear association of the BCC incidence with the cumulative skin absorbed dose of external gamma-ray exposure was observed: ERR/Gy = 0.57 (95% CI 0.24, 1.06). Inclusion of an adjustment for neutron dose in the model resulted in a modest reduction of the BCC risk estimate [ERR/Gy = 0.55 (95% CI 0.23, 1.03)]. No significant association was revealed for SCC incidence with cumulative skin absorbed dose of external gamma-ray exposure [ERR/Gy = 0.14 (95% CI -0.23, 0.91)]; inclusion of the neutron dose adjustment in the model did not modify the estimated SCC risk. No modification of the BCC and SCC incidence risks by sex, age at hire, attained age and facility type was observed.

-2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Chlebicka I, Stefaniak A, Matusiak Ł, Szepietowski JC. -2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma. Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. 2022. doi:10.5114/pdia.2015.55178. APA Chlebicka, I., Stefaniak, A., Matusiak, Ł., & Szepietowski, J. C. (2022). -2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma. Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. https://doi.org/10.5114/pdia.2015.55178 Chicago Chlebicka, Iwona, Aleksandra Stefaniak, Łukasz Matusiak, and Jacek C Szepietowski. 2022. "-2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma". Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. doi:10.5114/pdia.2015.55178. Harvard Chlebicka, I., Stefaniak, A., Matusiak, Ł., and Szepietowski, J. (2022). -2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma. Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. https://doi.org/10.5114/pdia.2015.55178 MLA Chlebicka, Iwona et al. "-2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma." Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology, 2022. doi:10.5114/pdia.2015.55178. Vancouver Chlebicka I, Stefaniak A, Matusiak Ł, Szepietowski J. -2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma. Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. 2022. doi:10.5114/pdia.2015.55178.

Risk of keratinocyte carcinomas with vitamin D and calcium supplementation: a secondary analysis of a randomized clinical trial

It is unknown whether dietary supplementation with vitamin D or calcium prevents keratinocyte carcinomas, also known as nonmelanoma skin cancers. This study aimed to determine whether daily vitamin D or calcium supplementation alters the risk of basal cell carcinoma (BCC) or invasive cutaneous squamous cell carcinoma (SCC). The Vitamin D/Calcium Polyp Prevention Study is a completed multicenter, double-blind, placebo-controlled, partial 2 × 2 factorial, randomized clinical trial of vitamin D, calcium, or both for the prevention of colorectal adenomas. During 2004-2008, a total of 2259 men and women, 45-75 y of age, recently diagnosed with a colorectal adenoma, were randomly assigned to 1000 IU/d of vitamin D3 or placebo and 1200 mg/d of calcium carbonate or placebo for 3 or 5 y, and followed after treatment ended. Reports of incident BCC or SCC were confirmed from pathology records. During a median follow-up of 8 y, 200 (9%) participants were diagnosed with BCC and 68 (3%) participants were diagnosed with SCC. BCC incidence was unrelated to treatment with vitamin D compared with no vitamin D (HR: 0.96; 95% CI: 0.73, 1.26), calcium compared with no calcium (HR: 1.01; 95% CI: 0.74, 1.39), and both agents compared with neither (HR: 0.99; 95% CI: 0.65, 1.51). SCC incidence was unrelated to treatment with vitamin D compared with no vitamin D (HR: 0.79; 95% CI: 0.49, 1.27), but there was suggestive evidence of beneficial treatment effects for calcium compared with no calcium (HR: 0.60; 95% CI: 0.36, 1.01) and both agents compared with neither (HR: 0.42; 95% CI: 0.19, 0.91). Calcium alone or in combination with vitamin D may reduce the risk of SCC, but not BCC. This trial was registered at clinicaltrials.gov as NCT00153816.

Vitamin D Receptor Polymorphisms and Non-Melanoma Skin Cancer Risk: A Case-Control Study.

Exposure to sunlight is the major source of vitamin D and the main environmental cause of non-melanocytic skin cancers. Vitamin D, partly mediated through the vitamin D receptor (VDR), has potential therapeutic applications in skin cancer. The aim of this study was to investigate the association of BsmI and ApaI VDR polymorphisms among patients with non-melanoma cancers and controls. An observational case-control study was conducted in a sample of 154 subjects. We observed no significant effects between these polymorphisms and skin cancer risk. When stratified for gender, GG and AG BsmI polymorphisms significantly increased the risk of basal cell carcinomas in males. In relation to ApaI, all three polymorphisms significantly increased the risk of basal cell carcinoma in males. When stratified for age, we found that being 70 years of age or younger was a protective factor against both skin cancers. Being a female and 70 years old or younger was a protective factor for basal cell carcinoma. A comparison of the frequencies of the VDR genotypes in patients older than 70 years vs. 70 years or younger also revealed age-dependent variations in patients with non-melanoma skin cancer. Our study suggests a role for VDR polymorphisms in non-melanoma skin cancer development.

Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant Recipients.

Keratinocyte cancers, which primarily comprise squamous cell carcinomas and basal cell carcinomas, represent a major concern and potential risk for kidney transplant recipients. Hydrochlorothiazide, a diuretic widely used to treat hypertension, has been implicated in skin photosensitivity reaction. Recent studies conducted in the general population have found that hydrochlorothiazide use is associated with a higher risk of keratinocyte cancer, especially squamous cell carcinomas. High-risk groups, however, including transplant recipients were excluded from these. Our aim was to investigate whether hydrochlorothiazide use was associated with keratinocyte cancer in kidney transplant recipients on immunosuppressive therapy. In a single-center cohort of kidney (n=2155), combined kidney-pancreas (n=282), and pancreas (n=59) transplant recipients from the Données Informatisées VAlidées Transplantation (DIVAT) database transplanted between 2000 and 2017 in Nantes, France, we evaluated the association between hydrochlorothiazide exposure and keratinocyte cancers. Multivariable cause-specific, time-varying Cox models were used to estimate the relationship between hydrochlorothiazide exposure and the hazard of squamous cell carcinoma and basal cell carcinoma, with hydrochlorothiazide designated as the time-dependent variable. Among the participants, 279 of 2496 (11%) were exposed to hydrochlorothiazide after the transplantation. Cumulative incidence rates of keratinocyte cancer by 10 and 15 years were 7% and 9% for squamous cell carcinomas, respectively, and 8% and 11% for basal cell carcinomas, respectively. We found a relationship between exposure to hydrochlorothiazide and the risk of squamous cell carcinomas (hazard ratio, 2.04; 95% confidence interval, 1.27 to 3.28). In contrast, we found no association between hydrochlorothiazide exposure and basal cell carcinomas (hazard ratio, 0.63; 95% confidence interval, 0.35 to 1.15). In a single-center cohort of kidney, combined kidney-pancreas, and pancreas transplant recipients, exposure to hydrochlorothiazide was associated with a two-fold higher risk of squamous cell carcinoma and no higher risk of basal cell carcinoma.

The Astounding Breadth of Health Disparity: Phenome-Wide Effects of Race on Disease Risk

ObjectiveWe conducted a phenotype-wide association study (PheWAS) to compare diagnoses among Blacks with those of Whites in one health center in Tennessee using data from 1,883,369 patients. MethodsWe used our deidentified EHR, the Synthetic Derivative, to assess risk of diagnoses associated with Black as compared with White race using Firth logistic regression with covariates including age, sex, and density of clinical encounters. ResultsThere were anchoring associations in both directions, including the highest increased risk for Blacks of having sickle cell anemia, and strongest decreased risk of basal cell carcinoma. Results included established areas of disparity and many novel associations. ConclusionsPheWAS is a viable tool for calculating risk associated with any biomarker. The current analysis provide a new approach to generating hypotheses and understanding the breadth of health disparities. Future analyses will further explore causality, risk factors, and potential confounders not accounted for here.