Slow N-acetylation as a possible contributor to bladder carcinogenesis.

Bladder cancer (BCa) is an exophytic tumor that presents as either noninvasive confined to the mucosa (NMIBC) or invading the detrusor muscle (MIBC), and was recently further subgrouped into molecular subtypes. Arylamines, major BCa environmental and occupational risk factors, are mainly metabolized by the genetically polymorphic N-acetyltransferases 1, NAT1 and NAT2. In this study, we investigated the association between N-acetyltransferases genetic polymorphism and key MIBC and NMIBC tumor biomarkers and subtypes. A cohort of 250 males with histologically confirmed urothelial BCa was identified. Tumors were genotyped for NAT1 and NAT2 using real-time polymerase chain reaction (PCR), and characterized for mutations in TP53, RB1, and FGFR3 by PCR-restriction fragment length polymorphism. Pathology data and patients' smoking status were obtained from medical records. Pearson χ2 and Fisher exact tests were used to check for associations and interactions. Results show that NAT1 G560 A polymorphism is significantly associated with higher muscle-invasiveness (MIBC vs NMIBC; P = .001), higher tumor grade (high grade vs low grade; P = .011), and higher FGFR3 mutation frequency within the MIBC subgroup (P = .042; .027). NAT2 G857 A polymorphism is also found to be significantly associated with higher muscle-invasiveness (MIBC vs NMIBC; P = .041). Our results indicate that slow N-acetylation is a contributor to bladder carcinogenesis and muscle-invasiveness. These findings highlight NAT1 as a biomarker candidate in BCa and a potential target for drug development.

Genetic polymorphisms of PPAR genes and human cancers: evidence for gene-environment interactions.

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in lipid metabolism, cell proliferation, terminal differentiation, apoptosis, and inflammation. Although several cancer models have been suggested to explain PPARs' involvement in tumorigenesis, however, their role is still unclear. In this review, we examined associations of the different PPARs, polymorphisms and various types of cancer with a focus on gene-environment interactions. Reviewed evidence suggests that functional genetic variants of the different PPARs may modulate the relationship between environmental exposure and cancer risk. In addition, this report unveils the scarcity of reliable quantitative environmental exposure data when examining these interactions, and the current gaps in studying gene-environment interactions in many types of cancer, particularly colorectal, prostate, and bladder cancers.

NAT1 genotypic and phenotypic contribution to urinary bladder cancer risk: a systematic review and meta-analysis.

N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline, PubMed, EMBASE, Scopus, Web of Science, OpenGrey, and BASE databases were searched to identify eligible studies. The random-effect model was used to calculate pooled effects estimates. Statistical heterogeneity was tested with Chi-square and I2. Twenty case-control studies, including 5606 cases and 6620 controls, met the inclusion criteria. Pooled odds ratios (OR) analyses showed a statistically significant difference in NAT1*10 versus non-NAT1*10 acetylators in the total sample (OR: 0.87; 95% CI: 0.79-0.96) but was borderline among Caucasians (OR: 0.88 with 95% CI: 0.77-1.01). No statistically significant differences in BCa risk were found for: NAT1*10 versus NAT1*4 wild type (OR: 0.97; 95% CI: 0.78-1.19), NAT1 'Fast' versus 'Normal' acetylators (OR: 1.03; 95% CI: 0.84-1.27), and NAT1 'Slow' versus 'Fast' (OR: 2.32; 95% CI: 0.93-5.84) or 'Slow' versus 'Normal' acetylators (OR: 1.84; 95% CI: 0.92-3.68). When stratifying by smoking status, no statistically significant differences in BCa risk were found for NAT1*10 versus non-NAT1*10 acetylators among the different subgroups. Our study suggests a modest protective role for NAT1*10 and a possible risk contributory role for slow acetylation genotypes in BCa risk. Further research is recommended to confirm these associations.

Bisphenol A exposure assessment from olive oil consumption.

The use of bisphenol A (BPA) in packaging has grown over the past 50 years despite concerns of its migration into packaged food and beverages, resulting in human exposure. Many studies have reported tumorigenic effects and endocrine alterations associated with BPA in animal models. This study aims at assessing human exposure to BPA from olive oil. A total of 27 olive oil samples were collected from mills and local villagers in the Hasbaya District, a major olive oil harvesting region in Lebanon. Information on storage conditions was also collected. BPA was extracted and quantified by HPLC. Results showed significantly higher BPA levels in olive oil samples stored in plastic vs. non-plastic packaging (mean = 333 vs. 150 µg/kg, p value = 0.006), samples with a plastic storage duration of >1 year compared to those with a storage duration of <1 year (mean = 452 vs. 288 µg/kg, p value = 0.008), and oil samples sourced from locals compared to oil mills (mean = 376 vs. 228 µg/kg, p value = 0.022). Statistically significant higher BPA levels remained for samples stored in plastic vs. non-plastic packaging in the bootstrap multivariable linear regression (B = 121.56, 95% CI 53.44-194.39, p value = 0.009). This is the first report on BPA levels in Mediterranean olive oil. The estimated exposure was 1.38% of the EFSA tolerable daily intake, hence there are no concerns about potential health risks from olive oil consumption.

Toxicogenetic profile and cancer risk in Lebanese.

An increasing number of genetic polymorphisms in drug-metabolizing enzymes (DME) were identified among different ethnic groups. Some of these polymorphisms are associated with an increased cancer risk, while others remain equivocal. However, there is sufficient evidence that these associations become significant in populations overexposed to environmental carcinogens. Hence, genetic differences in expression activity of both Phase I and Phase II enzymes may affect cancer risk in exposed populations. In Lebanon, there has been a marked rise in reported cancer incidence since the 1990s. There are also indicators of exposure to unusually high levels of environmental pollutants and carcinogens in the country. This review considers this high cancer incidence by exploring a potential gene-environment model based on available DME polymorphism prevalence, and their impact on bladder, colorectal, prostate, breast, and lung cancer in the Lebanese population. The examined DME include glutathione S-transferases (GST), N-acetyltransferases (NAT), and cytochromes P-450 (CYP). Data suggest that these DME influence bladder cancer risk in the Lebanese population. Evidence indicates that identification of a gene-environment interaction model may help in defining future research priorities and preventive cancer control strategies in this country, particularly for breast and lung cancer.

Exposure assessment of endocrine disruptors in bottled drinking water of Lebanon.

Bisphenol A (BPA) is a commonly used monomer in various products including bottled water. Numerous studies have reported endocrine adverse effects and neoplasia associated with BPA exposure in animals. However, considerable discrepancies exist among these studies with respect to both the nature of the toxic effects and the threshold dose. In Lebanon, 19-L polycarbonate (PC) bottles of drinking water are widely used in urban areas. The present study aims at assessing BPA human exposure and associated health risks from drinking water in Lebanese. A total of 22 bottled water sources, packaged in PC, were identified from licensed and non-licensed sources. Water samples were analyzed following exposure to sunlight for 72 h. BPA in water was quantified by HPLC, and other potential organic pollutants were screened by GC/MS. Fifty-nine percent of samples showed BPA levels above detection limits (>0.05 ng/mL). The median BPA level was 0.1 ng/mL (range 0.05 to 1.37 ng/mL). The mean BPA level for the total number of samples was 0.169 ng/mL (±0.280). A higher mean BPA level was found in water from licensed companies compared to non-licensed sources, however, not statistically significant. Screening showed the presence of dibutyl-phthalate and dioctyl-phthalate in only two samples. Endocrine disruptors (EDR) are ubiquitous contaminants in bottled water in Lebanon with potential health risk implications. Although estimated exposure levels are below the reference dose (RfD), further studies are needed to quantitate exposure from various sources and to investigate EDR contribution to existing epidemics in the country.

Cytotoxicity of water supply in a Palestinian refugee camp and a Syrian informal tented settlement in Lebanon.

Deficient water, sanitation, and hygiene (WASH) significantly account for a high burden of disease across the globe. Lebanon, an Eastern Mediterranean lower-middle-income country with a polluted environment, a fragmented healthcare system, and an ongoing severe economic crisis, faces serious challenges in sustaining safe water supplies, especially in vulnerable communities, while also hosting the world highest refugee population per capita. This study aimed to examine the mutagenicity, and the estrogenic and androgenic activities of water supplies, across both a Palestinian refugee camp and a Syrian informal settlement. Water samples were collected from two targeted camps in Dbayeh and Choueifat, North and South of the Capital City Beirut, respectively, between the months of September and October 2022. Microbial and physicochemical properties of samples were determined, including fecal contamination, total dissolved solids, and various minerals and salts. Organic pollutants were extracted using pre-packed solid phase extraction (SPE) columns, and then mutagenicity of extracts was examined using the Ames test in two Salmonella typhi bacterial strains. The estrogenic and androgenic activities of extracts were assessed using the yeast estrogen and androgen screen tests assays (YES/YAS). Results show excessive levels of total coliforms and total dissolved solids (TDS) in samples from both sites. In addition, the water supply from the Dbayeh Palestinian refugee camp is mutagenic, while the water supply from the Choueifat Syrian informal settlement shows anti-androgen activity. Our findings provide valuable WASH baseline data in two major vulnerable communities in Lebanon, and highlight the importance of a water toxicity testing approach concomitant with a water safety plan, based on a holistic strategy that covers all stages of the water supply chain.

Feature selection approaches for predictive modelling of cadmium sources and pollution levels in water springs.

The World Health Organization lists cadmium (Cd) as one of the top ten chemicals of public health concern. Cd is toxic at relatively low exposure levels and has acute and chronic effects on both health and the environment. In this study, we investigate a suite of data-driven methods that could assist decision-makers in estimating Cd levels in water springs, and in identifying polluting sources. Machine learning (ML) regression models were used to identify sources of contamination and predict Cd levels based on support vector machines and a variety of tree-based models, including Random Forests, M5Tree, CatBoost, and gradient boosting. Feature selection analysis revealed that heavy traffic and distance to a major power plant in the sampled area play a leading role in springs Cd contamination, together with precipitation levels and average of slopes of the closest waste dumps upstream to sampled springs. Our best performing ML model was the Adaboost regression tree using all the features (RMSE = 19.36, R^2 = 0.64). Our findings highlight the effectiveness of predictive data-driven modeling in addressing environmental challenges, particularly in high-risk areas with low resources.

Effect of BPA on CYP450s expression, and nicotine modulation, in fetal rat brain.

Human exposure to bisphenol A (BPA) is mainly due to migration from plastic packaging into food and beverages. Studies reported BPA endocrine disruptions through interactions with different nuclear receptors, including the arylhydrocarbon receptor (AhR). AhR mediates xenobiotic responses and regulates expression of drug-metabolizing enzymes (DMEs), including many CYP450s. This study aimed to assess the effects of BPA maternal exposure on CYP450s expression in fetal brain. Sprague-Dawley dams were exposed to BPA concentrations of 0, 0.5, 5, and 50 mg/L in drinking water, individually, and with nicotine. Fetal brains were isolated at gestational days GD14 and GD19, and protein expression was assessed by Western blotting. Results showed a BPA-induced significant decrease in CYP1B1 expression levels at GD14 (p = 0.001), and CYP19A1 (aromatase) expression at both mid- and late-stage development (p < 0.001). In addition, nicotine individually decreased expression levels of all examined protein targets, significantly for CYP1B1 (p < 0.001), CYP19A1 (p = 0.010), AhRR (p = 0.042), and ARNT (p < 0.001), compared to control. When combined with BPA, nicotine suppressive effects were attenuated at both GD14 and GD19. In conclusion, BPA suppresses CYP1B1 and CYP19A1 expression in fetal brain, and attenuates the suppressive effects of nicotine. Observed effects may be mediated by AhR-ARNT independent mechanisms that need further examination.

AhRR methylation contributes to disease progression in urothelial bladder cancer.

BACKGROUND: Bladder Cancer (BCa) is the tenth most incident malignancy worldwide. BCa is mostly attributed to environmental exposure and lifestyle, particularly tobacco smoking. The Aryl Hydrocarbon Receptor Repressor (AhRR) participates in the induction of many enzymes involved in metabolizing carcinogens, including tobacco smoke components. Additionally, studies have shown that smoking demethylates the (AhRR) gene in blood, suggesting AhRR demethylation as a specific serum smoking biomarker. OBJECTIVE: This study aimed to validate AhRR demethylation as a smoking biomarker in the target tissue and investigate its contribution to bladder carcinogenesis. METHODS: AhRR percent methylation was tested for its association with patient smoking status and oncogenic outcome indicators, particularly p53, RB1, and FGFR3 activating mutations, muscle-invasiveness, and tumor grade, in 180 BCa tissue-based DNA. RESULTS: Results showed significantly higher AhRR percent methylation in muscle-invasive compared to non-muscle invasive tumors (42.86% vs. 33.98%; p= 0.011), while lower AhRR methylation was significantly associated with FGFR3 Codon 248 mutant genotype compared to wild-type (28.11% ± 9.44 vs. 37.87% ± 22.53; p= 0.036). All other tested associations were non-statistically significant. CONCLUSIONS: Although AhRR methylation did not predict smoking status in BCa tumors, it may be a contributor to carcinogenesis and disease progression. Our findings constitute the basis for further research.

Serum Cadmium Levels and Risk of Metabolic Syndrome: A Cross-Sectional Study.

The increase in the prevalence of metabolic disorders globally is becoming a public health concern. Previous studies have reported an association between environmental exposures to hazardous substances, including various heavy metals, and the risk for metabolic syndrome. However, reports on the contributions of cadmium (Cd) to the risk for obesity and diabetes remain inconsistent. This study aims to investigate an association between serum Cd levels (SCL) and diabesity and dyslipidemia risk scores. A total of 140 subjects were identified from a public academic institution in Lebanon. Socio-demographic information, diabesity, and obesity risk scores were determined using an interview-based adapted FINDRISC questionnaire and analysis of an acquired blood sample. SCL was quantified using inductively coupled plasma mass spectrometry (ICP-MS). The statistical analysis relied on a chi-squared test and multivariate logistic regression models, along with checks for confounders and effect modifiers. Our results showed a Cd geometric mean of 4.04 µg/L (± 2.5). High SCL was significantly associated with higher dyslipidemia risk (OR: 3.05 [95% CI: 1.19-7.86], P = 0.02), even after adjusting for confounders. However, SCL did not show a statistically significant association with diabetes and obesity outcomes. Elevated SCL increases the risk of dyslipidemia and alters the blood lipid profile. In addition, our findings do not support a role for Cd in diabesity.

Beirut Ammonium Nitrate Blast: Analysis, Review, and Recommendations.

A massive chemical detonation occurred on August 4, 2020 in the Port of Beirut, Lebanon. An uncontrolled fire in an adjacent warehouse ignited ~2,750 tons of Ammonium Nitrate (AN), producing one of the most devastating blasts in recent history. The blast supersonic pressure and heat wave claimed the lives of 220 people and injured more than 6,500 instantaneously, with severe damage to the nearby dense residential and commercial areas. This review represents one of the in-depth reports to provide a detailed analysis of the Beirut blast and its health and environmental implications. It further reviews prior AN incidents and suggests actionable recommendations and strategies to optimize chemical safety measures, improve emergency preparedness, and mitigate the delayed clinical effects of blast and toxic gas exposures. These recommended actionable steps offer a starting point for government officials and policymakers to build frameworks, adopt regulations, and implement chemical safety protocols to ensure safe storage of hazardous materials as well as reorganizing healthcare system disaster preparedness to improve emergency preparedness in response to similar large-scale disasters and promote population safety. Future clinical efforts should involve detailed assessment of physical injuries sustained by blast victims, with systemic mitigation and possible treatment of late blast effects involving individuals, communities and the region at large.

Prenatal exposure to criteria air pollutants and associations with congenital anomalies: A Lebanese national study.

Maternal exposure to air pollution has been associated with a higher birth defect (BD) risk. Previous studies suffer from inaccurate exposure assessment methods, confounding individual-level variations, and classical analytical modelling. This study aimed to examine the association between maternal exposure to criteria air pollutants and BD risk. A total of 553 cases and 10,214 controls were identified from private and public databases. Two subgroups were then formed: one for a matched case-control design, and another for Feature Selection (FS) analysis. Exposure assessment was based on the mean air pollutant-specific levels in the mother's residential area during the specific BD gestational time window of risk (GTWR) and other time intervals. Multivariate regression models outcomes consistently showed a significant protective effect for folic acid intake and highlighted parental consanguinity as a strong BD risk factor. After adjusting for these putative risk factors and other covariates, results show that maternal exposure to PM2.5 during the first trimester is significantly associated with a higher overall BD risk (OR:1.05, 95%CI:1.01-1.09), and with a higher risk of genitourinary defects (GUD) (OR:1.06, 95%CI:1.01-1.11) and neural tube defects (NTD) (OR:1.10, 95%CI:1.03-1.17) during specific GTWRs. Maternal exposure to NO2 during GTWR exhibited a significant protective effect for NTD (OR:0.94, 95%CI:0.90-0.99), while all other examined associations were not statistically significant. Additionally, maternal exposure to SO2 during GTWR showed a significant association with a higher GUD risk (OR:1.17, 95%CI:1.08-1.26). When limiting selection to designated monitor coverage radiuses, PM2.5 maintained significance with BD risk and showed a significant gene-environment interaction for GUD (p = 0.018), while NO2 protective effect expanded to other subtypes. On the other hand, FS analysis confirmed maternal exposure to PM2.5 and NO2 as important features for GUD, CHD, and NTD. Our findings, set the basis for building a novel BD risk prediction model.

Quantitative cancer risk assessment and local mortality burden for ambient air pollution in an eastern Mediterranean City.

Health risks posed by ambient air pollutants to the urban Lebanese population have not been well characterized. The aim of this study is to assess cancer risk and mortality burden of non-methane hydrocarbons (NMHCs) and particulates (PM) based on two field-sampling campaigns conducted during summer and winter seasons in Beirut. Seventy NMHCs were analyzed by TD-GC-FID. PM2.5 elemental carbon (EC) components were examined using a Lab OC-EC aerosol Analyzer, and polycyclic aromatic hydrocarbons were analyzed by GC-MS. The US EPA fraction-based approach was used to assess non-cancer hazard and cancer risk for the hydrocarbon mixture, and the UK Committee on Medical Effects of Air Pollutants (COMEAP) guidelines were followed to determine the PM2.5 attributable mortality burden. The average cumulative cancer risk exceeded the US EPA acceptable level (10-6) by 40-fold in the summer and 30-fold in the winter. Benzene was found to be the highest contributor to cancer risk (39-43%), followed by 1,3-butadiene (25-29%), both originating from traffic gasoline evaporation and combustion. The EC attributable average mortality fraction was 7.8-10%, while the average attributable number of deaths (AD) and years of life lost (YLL) were found to be 257-327 and 3086-3923, respectively. Our findings provide a baseline for future air monitoring programs, and for interventions aiming at reducing cancer risk in this population.

Mercury health risk assessment among a young adult Lebanese population.

Mercury (Hg) exposure represents a significant public health concern at a global level. This study aims at assessing Hg exposure and risk among Lebanese young adults based on Hg biomonitoring and seafood intake. A group of 166 young adults were administered a questionnaire to assess Hg exposure and were asked to provide a hair sample. Risk assessment was performed: (1) using the US Environmental Protection Agency Hazard Quotient (HQ) model based on fish intake and previously studied local fish Hg concentrations, and (2) by determining the total hair Hg concentration (THHg) using continuous flow-chemical vapor generation atomic absorption spectrometry. Differences in THHg across demographic and exposure subgroups were tested using t test or ANOVA. Correlations between THHg concentrations, fish consumption, and HQ were determined by computing Pearson's r. Higher THHg correlated with higher consumption of Mediterranean rabbitfish/spinefoots (r = 0.27; p = 0.001) and geographical location (p < 0.001) in the bivariate analysis, and remained significant in the adjusted multivariable linear regression model (geographical location: ß = 0.255, 95%CI 0.121-0.388; rabbitfish/spinefoots consumption: ß = 0.016, 95%CI 0.004-0.027). No significant correlations were found between HQ and THHg. In conclusion, this is the first study examining hair Hg levels and fish consumption in a young adult Lebanese population. Our findings constitute valuable baseline data for a local fish advisory and Hg monitoring.

Cytochrome P450 CYP3A4/5 expression as a biomarker of outcome in osteosarcoma.

PURPOSE: Osteosarcoma, the most common pediatric primary bone tumor, is an aggressive malignancy with a tendency for early pulmonary metastasis. A reliable biomarker to predict clinical outcome at diagnosis has not yet been identified. To date, pathological review of neoadjuvant chemotherapy-induced necrosis is the most useful determinant of which patients are likely to develop metastatic disease. There is a clinical need to identify patients who will benefit from more aggressive preoperative therapy or perhaps require less aggressive chemotherapy. More than 30 human P450 isoenzymes have been characterized, with at least nine possessing some clinical relevance. One of these, CYP3A4/5 is involved in metabolic activation and detoxification of a wide number of carcinogens and chemotherapeutic agents, including many drugs that are useful in the treatment of osteosarcomas. MATERIALS AND METHODS: Osteosarcoma tissue microarray blocks containing biopsies from 18 primary tumors were used to analyze the expression of P450s 1A1/2, 1B1, 2B6, 2D6, and 3A4/5 by enzyme-linked avidin-biotin complexed immunohistochemistry. The frequencies of expression were 83%, 67%, and 83% for P450s 1A1/2, 1B1, and 3A4/5, respectively. P450s 2B6 and 2D6 were not detectable. RESULTS: These results were extended by developing a fluorescent-based quantitative immunocytochemistry technique to assess the levels of CYP3A4/5 in 18 paraffin-embedded primary biopsy sections. Expression of CYP3A4/5 was found to be significantly higher in primary biopsies of patients who developed distant metastatic disease compared with biopsies from patients with nonmetastatic disease (P = 0.0004). CONCLUSION: High cytochrome P450 CYP3A4/5 expression may predict metastasis and poor prognosis in osteosarcomas. Its use as a biomarker of therapeutic response will have implications for the treatment of these tumors.

Association of CYP3A4/5 genotypes and expression with the survival of patients with neuroblastoma.

Neuroblastoma (NB) is a rare pediatric disease in Lebanon for which poor prognosis remains a major challenge. Genetic polymorphism of genes coding for drug­metabolizing enzymes may influence the response of a patient to chemotherapy. This study investigates a possible association between CYP3A4/5 polymorphism and expression levels and survival in NB patients. All patients with stage III and IV NB diagnosed between 1993 and 2012 in three major hospitals in Beirut were included (n=27). Demographic information and survival time were obtained from medical records. CYP3A4 and CYP3A5 genotypes and expression levels were determined in archival tumors by polymerase chain reaction (PCR) and restriction fragment length polymorphism and quantitative PCR, respectively. Additionally, MYCN amplification was assessed. A Cox proportional hazards model was used to evaluate potential associations, adjusting for MYCN amplification. A statistically significant increase in the risk of mortality was observed in patients with MYCN amplification [hazard ratio (HR) 4.11, 95% confidence interval (CI) 1.14­14.80]. Patients with CYP3A5 expression levels above the median had a lower risk of mortality (HR 0.61, 95% CI 0.21­1.74) and patients with CYP3A4 expression levels above the median had a higher risk of mortality (HR 2.00, 95% CI 0.67­5.90). CYP3A5*3/*3 homozygote mutants had a 4.3­fold increase in the risk of mortality compared with that of homozygote wild­type or heterozygote mutants (HR 4.30, 95% CI 0.56­33.30). Carriers of the CYP3A4*1B mutant allele had a 52% lower risk of mortality compared with that of non­carriers (HR 0.48, 95% CI 0.06­3.76). Although the results of the present study did not achieve statistical significance, associations were observed, which indicates that CYP3A4 and CYP3A5 may modulate the clinical outcome of NB. Further studies with larger sample sizes are required to characterize the effects of the polymorphism and expression levels of CYP3A4/5 on the survival of patients with NB.

CYP2E1 and NQO1 genotypes and bladder cancer risk in a Lebanese population.

Urinary bladder cancer incidence in Lebanon ranks among the highest in the world. Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N-Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated in bladder cancer. The present study attempts to investigate the role of these DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and 106 controls were recruited from two hospitals in Beirut. An interview-based questionnaire was administered to assess suspected environmental and occupational risk factors. PCR-RFLP was performed on blood-based DNA samples to determine DMEs genotypes. Associations between bladder cancer and putative risk factors were measured using adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Results showed CYP2E1 c1/c1, NAT1*14A, and smoking, to be risk factors for bladder cancer. No significant differences in frequency distribution of the NQO1 genotypes were found in cases versus controls. The odds of carrying the CYP2E1 c1/c1 genotype were 4 times higher in cases compared to controls (OR=3.97, 95% CI: 0.48-32.7). The odds of carrying at least one NAT1*14A allele were 14 times higher in cases versus controls (OR=14.4, 95% CI: 1.016-204.9). Our study suggests CYP2E1 c1/c1, NAT1*14A, and smoking, as potential risk factors for bladder cancer in Lebanese. Further studies with larger samples must be conducted to confirm these findings.

N-Acetyltransferase 1 (NAT1) Genotype: A Risk Factor for Urinary Bladder Cancer in a Lebanese Population.

In Lebanon, bladder cancer is the second most incident cancer among men. This study investigates a possible association between N-acetyltransferase 1 (NAT1) genotype, a drug-metabolizing enzyme coding gene, and bladder cancer in Lebanese men. A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were conveniently identified and selected from the same settings. Data was collected using interview questionnaire and blood analysis. NAT1 genotypes were determined by PCR-RFLP. Statistical analysis revolved around univariate, bivariate, and multivariate logistic regression models, along with checks for effect modification. Results showed NAT1(∗)14A allele, smoking, occupational exposure to combustion fumes, and prostate-related symptoms, to be risk factors for bladder cancer. The odds of carrying at least one NAT1(∗)14A allele are 7 times higher in cases compared to controls (OR = 7.86, 95% CI: 1.53-40.39). A gene-environment interaction was identified for NAT1(∗)14A allele with occupational exposure to combustion fumes. Among carriers of NAT1(∗)14A allele, the odds of bladder cancer dropped to 2.03 from 3.72. Our study suggests NAT1(∗)14A allele as a possible biomarker for bladder cancer. Further research is recommended to confirm this association.