Risk Of Squamous Cell Carcinoma Research Articles

Anal cytology screening in men who have sex with men with HIV at a university hospital in Bogotá, Colombia.

Risk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV. This retrospective observational cohort study included MSM ≥18years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology. A total of 211 patients were included. Mean age was 35.6years. Sixty-eight (32.3%) had an abnormal anal cytology result: ASC-US 33.8% (n = 23); LSIL 60.3% (n = 41); and HSIL 5.9% (n = 4). MSM with an STI diagnosis in the previous 12 months (RR 1.48, [95% CI 1.03-2.12], p = 0.032) or with a CD4+ T cell count <200 (RR 2.08 [95% CI 1.16-3.73], p = 0.014) were significantly more likely to have abnormal anal cytology. These data provide crucial information to guide scale up of anal cancer screening at select centers in Colombia. Our results also suggest STI prevention efforts and improved virological control among MSM living with HIV may have the secondary benefit of reducing the risk of anal cancer.

Association Between Diabetes Risk Reduction Diet and Lung Cancer Risk in 98,159 Participants: Results From a Prospective Study.

PurposeTo evaluate the association between diabetes risk reduction diet (DRRD) score and the risk of lung cancer in a large population.MethodsData of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in the Cox proportional hazards regression model for the association of DRRD score and lung cancer incidence in all included participants. Prespecified subgroup analyses were performed to evaluate whether the observed association was modified by age, sex, BMI, race/ethnicity, family history of lung cancer, smoking status and history of diabetes.ResultsA total of 98,159 participants were included in this study. The mean (SD) age of the study participants cohort at baseline was 65.5 (5.73) years old. The mean (SD) follow-up time was 8.83 (1.96) years. The mean (SD) score of DRRD was 26.82 (5.19), and ranged from 20.47 (2.3) to 33.65 (2.42) from the lowest quartile to the highest quartile of the DRRD score, inferring the possibility of highest through the lowest risk of type 2 diabetes. The calculated HRs showed there was a trend that higher quartile indicated lower risk of lung cancer after adjusted for covariates (HRQ4vsQ1: 0.85; 95% CI:0.73,0.98; p for trend =0.036). The inverse trend between higher DRRD score and the risk of squamous cell carcinoma was more evident (HRQ4vsQ1: 0.50; 95% CI:0.34,0.73; p for trend =0.002). The inverse association between DRRD score and the incidence of lung cancer was more pronounced in participants who had a clear family history of lung cancer (p for interaction=0.016).ConclusionA protective association between DRRD score and risk of lung cancer is obtained. People are encouraged to adhere to higher DRRD score in their daily diet. Further studies should be conducted to confirm the result and explore the mechanism.

Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis

Treatment of actinic keratosis (AK) aims to prevent cutaneous squamous cell carcinoma (cSCC). However, whether AK can progress into invasive cSCC is a matter of debate, and little is known about the effect of treatment on preventing cSCC. To evaluate the risk of invasive cSCC and factors that may contribute to increased risk in patients with multiple AKs. In this secondary analysis of a multicenter randomized clinical trial, 624 patients with a minimum of 5 AKs within an area of 25 to 100 cm2 on the head were recruited from the Department of Dermatology of 4 hospitals in the Netherlands. Long-term follow-up was performed from July 1, 2019, to December 31, 2020. Patients were randomized to treatment with 5% fluorouracil, 5% imiquimod cream, methylaminolevulinate photodynamic therapy, or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with invasive cSCC in the target area during follow-up. Secondary outcomes were the associations between risk of invasive cSCC and a priori defined potential prognostic factors, including type of treatment, severity of AK (Olsen grade), history of nonmelanoma skin cancer, and additional treatment. Of the 624 patients (558 [89.4%] male; median age, 73 years [range, 48-94 years]) in the study, 26 were diagnosed with a histologically proven invasive cSCC in the target area during follow-up. The total 4-year risk of developing cSCC in a previously treated area of AK was 3.7% (95% CI, 2.4%-5.7%), varying from 2.2% (95% CI, 0.7%-6.6%) in patients treated with fluorouracil to 5.8% (95% CI, 2.9%-11.3%) in patients treated with imiquimod. In patients with severe AK (Olsen grade III), the risk was 20.9% (95% CI, 10.8%-38.1%), and the risk was especially high (33.5%; 95% CI, 18.2%-56.3%) in patients with severe AK who needed additional treatment. In this secondary analysis of a randomized clinical trial, risk of invasive cSCC was highest in patients with Olsen grade III AK and was substantially increased in patients who received additional treatment. These patients should be closely followed up after treatment. ClinicalTrials.gov Identifier: NCT02281682.

Atopic Dermatitis and Skin Cancer Risk: A Systematic Review.

IntroductionAtopic dermatitis (AD) is one of the most common skin diseases, and it may be associated with skin cancer risk. However, there is a controversy pertaining to whether it implies a greater or decreased risk of skin cancers. We aimed to study the relationship between AD and skin cancer risk.MethodsPubMed and Embase databases from their inception to 4 August 2021 were systematically searched.ResultsWe evaluated 16 studies involving a total of 9,638,093 participants examining the contribution of AD to skin cancers. Random-effects model was applied to estimate the overall effect sizes. The pooled analysis of 16 studies indicated that AD was significantly associated with an overall increased risk of skin cancer. Subgroup pooled analyses showed that AD was statistically associated with an increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). With regard to cohort study, AD was statistically associated with an increased risk of nonmelanoma skin cancer (NMSC), BCC, and SCC, but not melanoma risk. Sensitivity analysis revealed that excluding each study in turn did not alter the overall combined results. No publication bias existed among the studies.ConclusionIt can be concluded that AD is associated with risk of skin cancers; however, this association still needs to be verified in well-designed, worldwide trials (especially prospective, non-Western studies). The mechanism of AD leading to skin cancer is not clear, and further research is needed to explore the possibility of a potential pathogenesis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00720-2.

Hot Tea Consumption and Esophageal Cancer Risk: A Meta-Analysis of Observational Studies

ObjectiveMany laboratory studies have shown that tea consumption protected against the development of esophageal cancer (EC). However, in epidemiological studies, inconsistent or even contradictory results were frequently observed, especially when drinking tea at higher temperatures.MethodsWe conducted a meta-analysis based on published observational studies to explore whether hot tea consumption was a risk factor of EC. Relevant studies were searched in PubMed, Embase, and Web of science up to October 13, 2021, and we also manually retrieved the literature in the included studies and recent reviews.ResultsA total of 23 eligible reports were identified, including 5,050 cases and 10,609 controls, and a meta-analysis with Comprehensive Meta-Analysis (CMA) software (version 2.0) was conducted. A statistically significant increased EC risk was observed when drinking tea at higher temperature (odds ratios (ORs) = 1.79, 95% CI: 1.48–2.15, p = 0.00). Except for esophageal adenocarcinoma (EAC), this increased risk was also found in the majority of subgroups, which are the European and Australian populations.ConclusionsThis meta-analysis showed that people who drank hot tea had a significantly increased risk of Esophageal squamous cell carcinoma (ESCC), but no significant association for EAC.

Laser Therapy for the Treatment of Actinic Cheilitis: A Systematic Review.

Actinic cheilitis (AC) is a chronic inflammation of the lip considered an oral, potentially malignant disorder associated with an increased risk of lip squamous cell carcinoma (SCC) development. Controversies surrounding current therapeutic modalities of AC are under debate, and the implications of laser treatment have not been specifically investigated through a systematic review design. The present study aims to evaluate the degree of evidence of laser for the treatment of AC in terms of efficacy and safety. We searched for primary-level studies published before January 2022 through MEDLINE/PubMed, Embase, Web of Science, Scopus and CENTRAL, with no limitation in publication language or date. We evaluated the methodological quality and risk of bias of the studies included using the updated Cochrane Collaboration’s tool for assessing risk of bias (RoB-2). Twenty studies (512 patients) met our eligibility criteria. Laser therapy showed a complete clearance of AC in 92.5% patients, with a maximum recurrence rate of 21.43%, and a very low frequency of malignant transformation to SCC (detected in only 3/20 studies analyzed). In addition, cosmetic outcomes and patient satisfaction were described as excellent. In conclusion, our findings indicate that laser therapy is a high efficacy approach to AC.

The Association Between Cyclooxygenase-2 -1195G/A (rs689466) Gene Polymorphism and the Clinicopathology of Lung Cancer in the Japanese Population: A Case-Controlled Study.

The single nucleotide polymorphisms of COX-2 gene, also known as PTGS2, which encodes a pro-inflammatory factor cyclooxygenase-2, alter the risk of developing multiple tumors, but these findings are not consistent for lung cancer. We previously reported that the homozygous COX-2 –1195A genotype is associated with an increased risk for chronic obstructive pulmonary disease (COPD) in Japanese individuals. COPD is a significant risk factor for lung cancer due to genetic susceptibility to cigarette smoke. In this study, we investigated the association between COX-2 –1195G/A polymorphism and lung cancer susceptibility in the Japanese population. We evaluated the genotype distribution of COX-2 –1195G/A using a polymerase chain reaction-restriction fragment length polymorphism assay for 330 newly diagnosed patients with lung cancer and 162 healthy controls. Our results show that no relationship exists between the COX-2 –1195G/A polymorphism and the risk of developing lung cancer. However, compared to the control group, the homozygous COX-2 –1195A genotype increased the risk for lung squamous cell carcinoma (odds ratio = 2.902; 95% confidence interval, 1.171–7.195; p = 0.021), whereas no association is observed with the risk for adenocarcinoma. In addition, Kaplan-Meier analysis shows that the genotype distribution of homozygous COX-2 –1195A does not correlate with the overall survival of patients with lung squamous cell carcinoma. Thus, we conclude that the homozygous COX-2 –1195A genotype confers an increased risk for lung squamous cell carcinoma in Japanese individuals and could be used as a predictive factor for early detection of lung squamous cell carcinoma.

Many hands make light work: CNV of GSTM1 effect on the oral carcinoma risk

BackgroundGenetic alterations of oral squamous cell carcinoma (OSCC) allow the understanding of the oral carcinogenesis and the identification of molecular biomarkers that aid the early diagnosis of the disease. The copy number variation (CNV) of GSTM1 and GSTT1 are promising targets because these two genes codify enzymes that perform the inactivation of tobacco carcinogens, which are the main risk factor of OSCC. However, the different levels of - detoxification mechanism in relation to each copy of the genes are unknown. Therefore, this study aimed to investigate the possible association of the CNV of GSTM1 and GSTT1 with the risk of development of OSCC. MethodsA total of 234 OSCC patients and 422 patients without any cancer diagnoses were recruited from Heliópolis Hospital from 2000 to 2011. The CNV was determined by TaqMan real-time PCR and the CopyCaller software. Odds ratio (OR) and 95% confidence interval (95% CI) values were calculated by Multiple Logistic Regression. ResultsMost OSCC patients reported they continued smoking high amounts of cigarettes despite the tumor diagnosis. The CNV of GSTM1 varied from zero to two copies and the analysis revealed that two copies of GSTM1 decreased by 53% the OSCC risk (OR 0.47; 95% CI 0.24–0.92) and the risk of the tumor was modified according to the interaction of the CNV of GSTM1 and the cigarette smoking consumption, which for the amount of 40 packs-year of cigarettes the OSCC risk diminished progressively according to the increase of copies of GSTM1. Although the GSTT1 gene varied from zero to three copies, none of them were associated with the tumor risk. ConclusionThe findings suggest that the CNV of GSTM1 might be applied as a tool for the surveillance of patients and the early detection of OSCC.

Identification of genetic instability in peripheral blood lymphocyte of oral squamous cell carcinoma patients assess by comet assay.

Context:Studies established that human cancer is principally a genetic disease; it arises as accumulation of a set of genetic changes. In the pathogenesis of cancer, genetic instability is the sequential event to a carcinogenic stimulus resulting in various genomic changes including DNA damage.Aims:To assess genetic instability, as susceptibility to DNA damage, we used single-cell gel electrophoresis (comet assay) to study double strand breaks in associated with the risk of oral squamous cell carcinoma (OSCC).Materials and Methods:We used comet assay to measure double strand break in individual peripheral blood lymphocytes from 50 individuals with OSCC and 30 healthy control subjects. All personal information was gathered from subjects including tobacco history. DNA damage was visualized as comet assay and quantified by movement of damaged strands as length of tail.Results:Study results of OSCC patients were observed in relation to clinical staging and histological grading of carcinoma. On the basis of clinical observation, cases were grouped in to Stage I, Stage II, Stage III and Stage IV. No stage I cases were in study sample. The mean DNA damage migration length was observed 4.600 ± 0.4613 μm in stage II, whereas in Stage III and Stage IV, it was observed to be 4.961 ± 0.5620 μm and 4.883 ± 0.410 μm, respectively. The DNA damage length in histological grades of squamous cell carcinoma patients in Grade I was 4.6437 ± 0.3061 μm and Grade II was 5.3533 ± 0.3831 μm. In comparison with control group and squamous cell carcinoma group, it was observed in the range of 0.02–0.36 μm and varied from 4.04 to 5.84 μm range, respectively. Thus, the results were statistically significant with the histological grading of OSCC.Statistical Analysis:Unpaired' test and “ANOVA” test are used for statistics.Statistical Analysis:Unpaired' test and “ANOVA” test are used for statistics.Conclusion:The amount of DNA strand breaks in peripheral lymphocytes are measured by comet assay which is associated with relative risk of OSCC.

Measuring ultraviolet exposure to the face in patients with xeroderma pigmentosum

British Journal of DermatologyVolume 186, Issue 4 p. e184-e184 Plain Language Summary Measuring ultraviolet exposure to the face in patients with xeroderma pigmentosum First published: 04 April 2022 https://doi.org/10.1111/bjd.21078AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Sarkany et al. Br J Dermatol 2022; 186:713–720. Xeroderma pigmentosum (XP) is a genetic disease in which the system that repairs damage caused by ultraviolet (UV) radiation (which mainly comes from the sun) is faulty. Patients with XP develop eye and skin cancers from childhood and usually die in early adulthood. The main means of preventing the cancers and increasing lifespan is extreme protection against the UV found in daylight, particularly for the face, which is where the cancers mostly occur. Not enough is known about how well patients with XP protect against UV radiation. In this paper, with authors from the UK, the Netherlands and Denmark, a new method was used to estimate face exposure in 36 patients with XP over 3 weeks in the summer. The method combines measurements from a wrist-worn UV detector with an ‘activity diary’ of what patients did to protect their face when outside. Some patients with XP protected themselves well whereas others did not. The difference between the face UV dose in the best and worst protecting patients was over 100-fold. Those patients protecting themselves the least from UV exposure had exposure levels similar to healthy adults. Adults and children with XP had similar exposure to UV but achieved it differently. Adults protected less well when outside but went outside less whereas children went outside more but protected better. This variation in UV exposure is important. Poor protection in patients with XP is likely to cause cancers and premature death. As well as being useful in XP, this new method to estimate facial UV exposure may also be useful in other more common diseases, particularly patients at high risk of basal and squamous cell carcinomas, which are mostly caused by UV and mainly affect the face. Volume186, Issue4April 2022Pages e184-e184 RelatedInformation

Dietary fatty acid patterns and risk of oesophageal squamous cell carcinoma.

BackgroundTo characterize and examine the associations between dietary fatty acid intake patterns and the risk of oesophageal squamous cell carcinoma (ESCC).MethodsA total of 422 patients and 423 controls were recruited. Dietary fatty acids were entered into a factor analysis. Multivariable logistic regression and restricted cubic spline were used to evaluate the risk of ESCC specific for different dietary fatty acid patterns (FAPs). A forest plot was applied to show the association between FAPs and ESCC risk after stratification by lifestyle exposure factors (tobacco smoking, alcohol drinking, pickled food, fried food, hot food, hard food).ResultsThe factor analysis generated four major fatty acid patterns: a medium- and long-chain SFA (MLC-SFA) pattern; an even-chain unsaturated fatty acid (EC-UFA) pattern, a saturated fatty acid (SFA) pattern and an n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) pattern. In the multivariate-adjusted model, the odds ratios (ORs) with 95% confidence intervals (CIs) of ESCC were 2.07 (1.31, 3.26) and 0.53 (0.34, 0.81) for the highest versus the lowest tertiles of the EC-UFA pattern and n-3 LC-PUFA pattern, respectively. The MLC-SFA and SFA patterns were not associated with ESCC. An association between FAPs and ESCC risk after stratification by lifestyle exposure factors was also observed.ConclusionsOur study indicates that the EC-UFA pattern and n-3 LC-PUFA pattern intake are associated with ESCC, providing a potential dietary intervention for ESCC prevention.

Life Course Tobacco Smoking and Risk of HPV-Negative Squamous Cell Carcinomas of Oral Cavity in Two Countries

BackgroundTobacco smoking remains one of the major risk factors for oral cavity cancers (OCC), a subgroup of head and neck cancer (HNC) less attributed to human papillomavirus (HPV) infection. Although a strong dose-dependent association between tobacco smoking and OCC exists, several important questions on the age-dependent effects of this habit remain unanswered. We investigated which life course hypothesis best describes the association between tobacco smoking and HPV-negative (HPV−ve) OCC in Canada and India.MethodsWe used data from the HeNCe Life study, a hospital-based case-control study conducted in Canada and India, using similar protocols. Cases were newly diagnosed subjects with primary squamous cell carcinomas of the head and neck region. Control subjects were patients with non-cancer selected from various outpatient clinics in a hospital located in the same catchment area as the cases and frequency-matched to cases according to age and sex. We collected information on an array of life course exposures using a structured questionnaire with the help of a life grid. Tobacco exposure (pack-years) during three life periods (≤ 30, 31−50, and >50 years of age) was calculated from the entire life course history of smoking. We used CDx brushes to collect oral exfoliated cells. Alpha HPV DNA detection and genotyping were performed for 36 HPV genotypes using the linear array. Participants who tested positive for HPV were excluded from the analysis. We used the Bayesian relevant life course exposure model (BRLM) to identify the life course hypothesis that best described the relationship between tobacco smoking and HPV−ve OCC.ResultsWe show evidence for a late-life sensitive period (>50 years of age) for tobacco smoking in relation to the risk of HPV−ve OCC in both Canada and India. An increase of 1 pack-year of tobacco smoking increased the risk of OCC by ~3% in both countries.ConclusionOur findings from the Canadian and Indian data suggest that smoking tobacco after 50 years of age may carry a higher risk of developing oral cancer than earlier in life. Further studies are warranted to confirm the results.

Does hydrochlorothiazide increase the incidence of skin, lip and oral cancer in a UK population?

Data sources Data was from The Health Improvement Network (THIN) database from January 1999 to May 2016.Study selection This was a series of population-based, case-control studies looking to evaluate the association between hydrochlorothiazide (HCTZ) exposure and skin, lip and oral cancer in the UK population.Case/control selection Using the THIN database, patients with the following outcomes were grouped: squamous cell carcinoma (SCC) skin cancer; basal cell carcinoma (BCC) skin cancer; melanoma; lip cancer and oral cancer. Patients within the lip cancer and oral cancer groups were accepted with a history of non-melanoma skin cancer (NMSC). Patients in the SCC and BCC groups were not accepted with a history of cancer. Patients with a history of organ transplantation, human immunodeficiency virus (HIV) or immunosuppressant drug use before the index date were not accepted, due to the risk of predisposition to cancer. Controls were randomly selected using incidence density sampling. Up to 100 controls were randomly selected, matched on sex, exact year of birth and calendar year of cohort entry for lip cancer. However, for the remaining outcomes, only 20 controls were matched as above. Adults with incident NMSC, melanoma, lip cancer and oral cancer were matched to controls. Incidence rate ratios (IRRs) for the aforementioned outcomes were calculated for every cumulative HCTZ exposure.Data analysis Odds ratios were calculated using conditional logistic regression. Associations were presented using a two-year HCTZ exposure lag-time and a five-year HCTZ exposure lag-time. Associations were evaluated using sensitivity analysis, restricted to patients with at least ten years' follow-up. There was adjustment for smoking status and BMI. Published incidence rates were used to calculate the absolute risk estimate for SCC as the incidence of SCC in the cohort was less than expected. For high-dose cumulative HCTZ exposure, the number of patients needed to treat to cause one additional cancer (number needed to harm) per year overall was estimated using rate differences. Analysis was carried out using SAS Enterprise Guidev7.1 and STATAv15.Results Relative incidence of SCC, BCC and lip cancer was significantly elevated with every use of HCTZ. Relative incidence of melanoma and oral cancer was not significantly elevated with HCTZ exposure. Smoking was inversely associated with BCC and melanoma risk, but significantly increased the risk of lip and oral cavity cancers. SCC risk was not strongly associated with smoking. Significantly reduced risk of SCC, BCC melanoma and oral cavity cancer was associated with a BMI ≥30 kg/m2.Conclusions The risk of NMSC and lip cancer in a UK population is increased with cumulative high-dose HCTZ exposure. It is therefore important for dentists to note as it may increase suspicion of lesions in patients taking these medications.

What is the malignant transformation potential of oral lichen planus?

Data sources In this systematic review and meta-analysis, Medline, Scopus and Web of Science databases were searched using Medical Subject Headings (MeSH) to identify studies assessing the risk of malignant transformation in oral lichen planus (OLP).Study selection Observational studies published in English between 2003-2020 were independently assessed for inclusion by two blinded investigators.Data extraction and synthesis Data were extracted independently by two investigators followed by discussion to reach consensus. This included: study design and patient characteristics; length of follow-up; risk of bias; method of OLP diagnosis; oral squamous cell carcinoma (OSCC) risk factors; rate of malignant transformation; and individual characteristics of malignant transformation cases. Cases of malignant transformation in the included studies were only included in meta-analysis if: 1) OLP diagnosis met current diagnostic criteria; 2) OSCC developed in the same site as previously diagnosed OLP after at least six months' follow-up; 3) the patient had no history of systemic immunosuppressive therapy, head and neck malignancy, or organ transplantation. Risk of bias was assessed using the modified Newcastle-Ottawa scale, and meta-analysis was conducted to estimate overall risk of OLP malignant transformation using the DerSimonian and Laird method. Pooled univariate odds ratios (OR) for malignant transformation were calculated based on gender, smoking status, alcohol consumption, hepatitis C infection and OLP subtype.Results In total, 593 studies were identified after removal of duplicates and 33 studies were included for data extraction. The included sample comprised 12,838 patients with OLP, and 151 malignant transformation cases were reported in the included studies. The authors excluded 56 malignant transformation cases from the meta-analysis, most commonly because of the absence of pathological OLP diagnosis. Among included malignant transformation cases, the mean (SD) age was 58.1 (12.4) years, and 64% of the sample was female. Random-effects meta-analysis estimated an OLP malignant transformation rate of 0.2% (95%CI: 0.1-0.3%). Heterogeneity was low (I2 = 28.74%, p = 0.065). Malignant transformation was significantly higher among smokers (OR = 4.62, p = 0.001), alcohol consumers (OR = 3.22, p = 0.05), those with hepatitis C (OR = 3.77, p = 0.03) and atrophic or erosive OLP subtypes (OR = 2.70, p = 0.03). Gender was not associated with increased risk of malignant transformation.Conclusions The malignant transformation rate of OLP is likely to be lower than previously reported, possibly as a result of variable diagnostic criteria. Whilst encouraging, clinical vigilance remains necessary, as OLP does carry a small risk of malignant transformation. Smoking, alcohol use, hepatitis C infection and erosive or atrophic subtypes appear to have a greater rate of malignant transformation.

Dietary antioxidant supplements and risk of keratinocyte cancers in women: a prospective cohort study.

Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate the associations between antioxidant supplement intake and keratinocyte cancer (KC) risk. E3N is an ongoing prospective cohort initiated in 1990 and involving 98,995 French women aged 40-65years at recruitment. Intakes of dietary antioxidants were estimated via a validated dietary questionnaire in 1993 and self-reported antioxidant supplement use was collected in 1995. We used Cox models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and skin cancer risk factors. Over 1995-2014, 2426 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KC risk (HR = 1.37, 95% CI 1.15-1.62), particularly with BCC (HR = 1.40, 95% CI 1.17-1.69); and between vitamin E supplement use and risks of both BCC (HR = 1.21, 95% CI 1.03-1.52) and SCC (HR = 1.43, 95% CI 1.03-1.99). Intake of beta-carotene supplements was associated with an increased SCC risk (HR = 1.59, 95% CI 1.00-2.54). Vitamin C supplement use was not associated with KC risk. We found similar results when considering total antioxidant intake. Intakes of vitamin A or E supplements were associated with an increased KC risk in women. Further studies with information on doses and duration of supplement use and the ability to examine their underlying mechanisms are needed.

Hydrochlorothiazide use is associated with the risk of cutaneous and lip squamous cell carcinoma: A systematic review and meta-analysis.

The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development. We performed a systematic review and meta-analysis of case-control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0). A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71-1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg. Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development.

Gene-gene and gene-environment interaction: An important predictor of oral cancer among smokeless tobacco users in Karachi.

To determine the risk for oral cancer caused by simultaneous occurrence of more than one of the tested cytochrome P450 CYP1A1 MspI, glutathione S-transferase M1 null gnd Glutathione S-transferases T1 null gene polymorphisms. The cross-sectional case-control study was conducted from December 2011 to October 2016 at the Ziauddin University, Karachi, in collaboration with Dow University of Health Sciences, Karachi, and comprised oral squamous cell carcinoma cases in group A and healthy tobacco habit-matched controls in group B. All investigations were done using standardised laboratory protocols. The outcomes were determined in terms of association of various combinations of cytochrome P450 1A1MspI, glutathione S-transferasesM1 null and glutathione S-transferases T1 null polymorphisms with oral cancer. Data was analysed using SPSS 20. Of the 238 subjects, 140(58.8%) were in group A and 98(41.2%) were in group B. Mean ages in group A and B were 47.1±12.22 and 41.6±14.58 years, respectively. Male/Female ratio in group A was 1.88:1 while 83.4% were using tobacco. When cytochrome P450 1A1MspI homozygous (m2/m2) and glutathione S-transferases M1 null variants occured simultaneously in an individual, an odds ratio of 12.8 (95% confidence interval: 1.20-135.5; p=0.03) among overall tobacco chewers was observed. For glutathione S-transferases M1 not null and glutathione S-transferases T1 null variant combination among overall tobacco users, the conferred odds ratio was 4.58 (95% confidence interval: 0.99-21.2; p=0.05). The other studied gene combinations did not reveal significant associations (p>0.05). A higher risk of oral squamous cell carcinoma was found to be associated with combined-gene polymorphisms of phase I and phase II enzymes than that attributed to a single-gene polymorphism.

The Single Nucleotide Polymorphisms of AP1S1 are Associated with Risk of Esophageal Squamous Cell Carcinoma in Chinese Population.

BackgroundThe σ1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of AP1S1 among Chinese population.MethodsA database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P<0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step.ResultsAP1S1 rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers.ConclusionAP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.

Dietary intake of monounsaturated and polyunsaturated fatty acids is related to the reduced risk of esophageal squamous cell carcinoma

BackgroundThe relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk.MethodsThis case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model.ResultsWhen comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21–0.51), PUFA (OR: 0.32, 95% CI: 0.20–0.51), and TFA (OR: 0.44, 95% CI: 0.28–0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19–0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC.ConclusionsThis study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.

Chemoprevention of cutaneous squamous cell carcinoma and its precursors in solid organ transplant recipients using topical sirolimus: A randomized, double-blind, placebo-controlled pilot trial

To the Editor: Immunosuppression in solid organ transplant recipients (SOTR) greatly increases the risk of keratinocyte cancer (KC), indisputably a significant burden in terms of morbidity, mortality, and cost. Switching calcineurin inhibitors to sirolimus is a major strategy that has resulted in a two-fold reduction in the risk of squamous cell carcinomas (SCC) but is poorly tolerated with many serious adverse events.1,2