Simple predictors of nonresponse to direct-acting antivirals in chronic hepatitis C patients.

OBJECTIVES: The introduction of direct acting antivirals (DAAs) has resulted in very high sustained virological response rates (SVR) in patients with chronic hepatitis-C (CHC). There are still a minority who fails to achieve SVR. This study aims to identify simple factors associated with nonresponse to DAAs using routine pretreatment workup. METHODS: A retrospective study included 10 655 CHC patients who were candidates for anti-viral therapy. Pretreatment demographics, laboratory results, ultrasonography and FIB-4were obtained. RESULTS: At post-treatment week 4, 10 495 patients (98.5%) were responders and 160 (1.5%) were non-responders. About 50.6% of non-responders were males and 61.3% were cirrhotic. Non-responders had significantly higher baseline BMI, liver enzymes, AFP and a significantly lower albumin, platelet count by univariate analysis ((P < 0.001). Sex, previous treatment, BMI, liver cirrhosis, AST, Albumin and platelet counts were the independent predictors of non-response. At post-treatment week 12, HCV-PCR results were available only for 7259 patients and 210 (2.9%) were non-responders. 54.8% of non-responders were cirrhotic and 51.4% were males. Non-responders had significantly higher AST, AFP and INR and a significantly lower albumin level, platelet count by univariate analysis (P < 0.05). Sex, previous treatment, AST, Albumin, WBC and platelet counts were the independent predictors of non-response. SVR-4 among treatment naive patients was 98.6% while among treatment experienced was 96.8%. SVR-12 among treatment naive patients was 97.9% while among treatment experienced was 87.9%.Cirrhotics had SVR-4 rate 97.7% and SVR-12 rate 96.21%. CONCLUSION: Routine pre-treatment work up for HCV G4 patients receiving DAAs can help in prediction of non-response.

Circumstances of Substance Use by Street Youth in Egypt Support the Case for Intervening to Prevent Adverse Childhood Experiences.

BACKGROUND: Egyptian street youth use substances including tobacco, illicit drugs, and pharmaceutical drugs. To understand the circumstances, including adverse childhood experiences, that place adolescents at risk for engaging in substance use, we conducted in-depth interviews among a sample of Egyptian street children. METHODS: From youth residing at or attending Caritas, a non-profit organization, which provides shelter and education to street youth, seven girls and twelve boys, aged 12 to 18 years, participated in open-ended, in-depth interviews. RESULTS: Eight out of the 19 participants reported family history (early exposure) to substance use; and seven of them were initiated by either a family member (sibling), friend or coworker. Most of the participants reported a history of conflict with or abuse (verbal or physical) by their parents or siblings, or stressful situations at home; they used substance(s) to alleviate their stress. Few attended school, and some were forced to work and help their family. CONCLUSIONS: Among Egyptian youth, adverse childhood experiences, such as poverty, child abuse, and family substance use, challenge somewhat susceptible youths and lead them to the path of substance use and addiction. Prevention intervention should be multifaceted, culturally adaptable, and primarily targeting the social environment during childhood.

Spontaneous Viral Load Decline and Subsequent Clearance of Chronic Hepatitis C Virus in Postpartum Women Correlates With Favorable Interleukin-28B Gene Allele.

BACKGROUND: Postpartum hepatitis C viral (HCV) load decline followed by spontaneous clearance has been previously described. Herein we identify predictors for viral decline in a cohort of HCV-infected postpartum women. METHODS: Pregnant women at Cairo University were screened for anti-HCV antibodies and HCV RNA, and viremic women were tested for quantitative HCV RNA at 3, 6, 9, and 12 months postpartum. Spontaneous clearance was defined as undetectable viremia twice at least 6-months apart. Associations between viral load and demographic, obstetrical, HCV risk factors, and interleukin-28B gene (IL28B) polymorphism (rs12979860) were assessed. RESULTS: Of 2514 women, 97 (3.9%) had anti-HCV antibodies, 54 (2.1%) were viremic and of those, 52 (2.1%) agreed to IL28B testing. From pregnancy until 12 months postpartum, IL28B-CC allele women had a significant viral decline (P = .009). After adjusting, the IL28B-CC allele had a near significant difference compared to the CT allele (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.75,1.00; P = .05), but not the TT allele (OR, 0.91; 95% CI, 0.61,1.38; P = .64). All 14/52 (26.9%) women who subsequently cleared were among the 15 with undetectable viremia at 12 months, making that time point a strong predictor of subsequent clearance (sensitivity = 100%, specificity = 97.4%, positive predictive value = 93.3%, negative predictive value = 100%). CONCLUSIONS: IL28B-CC genotype and 12-month postpartum undetectable viremia were the best predictors for viral decline and subsequent clearance. These 2 predictors should influence clinical decision making.

Use of personal digital assistants to detect healthcare-associated infections in a neonatal intensive care unit in Egypt.

INTRODUCTION: Personal digital assistants (PDAs) used in electronic laboratory-based surveillance are a promising alternative to conventional surveillance to detect healthcare-associated infections (HAIs). The aim of the study was to monitor, detect, and analyze HAIs using PDAs in a neonatal intensive care unit (NICU). METHODOLOGY: In this descriptive study, 1,053 neonates admitted to the NICU in the obstetrics and gynecology ward at the Cairo University hospital were included and evaluated for HAIs by collecting data using PDAs programmed by Naval Medical Research Unit 3, Cairo, with the definitions for HAIs provided by the National Healthcare Safety Network of the Centers for Disease Control and Prevention. Case records were reviewed three times a week over 19 months, from March 2012 to September 2013. RESULTS: Of 124 suspected episodes of infection recorded in PDAs, 89 confirmed episodes of infection were identified. HAI and NICU infection rates were 7.4 and 2.72/1,000 patient-days, respectively. Primary bloodstream infection was detected in 81 episodes and pneumonia in 8 episodes. The majority of infections (62%) were acquired in the ward before NICU admission. Klebsiella spp. was isolated most frequently (42%), followed by coagulase-negative Staphylococci (31%). CONCLUSIONS: This study is the first to report the use of PDAs in surveillance to detect HAIs in the NICU in our hospital. The majority of infections were acquired at the obstetric care department, indicating the importance of implementing rigorous prevention and control programs and a more detailed surveillance to identify other risk factors for infections.

Parental perceptions of congenital cardiovascular malformations in their children.

We assessed parental attitudes towards congenital cardiovascular malformations in their children in a cross-sectional study in Egypt. Parents face many problems related to concerns about their child's prognosis, but these associations with parental stress have never been evaluated in Egypt or examined in relation to religiosity in a predominantly Muslim society. Accordingly, we conducted interviews in Cairo with mothers of 99 sequential infants born with conotruncal heart malformations (cases) and 65 mothers of age-matched controls. The survey assessed healthcare access and usage, knowledge of congenital cardiovascular malformations, religiosity, the Locus of Control Scale, and the Parenting Stress Index. Results showed that 45% of the mothers of cases had correct knowledge about their child's diagnosis; 85% were satisfied with the clinical care; and 79% reported that the cost of care was burdensome. Compared with parents of cases, parents of controls were more likely to report stress overall and all its subscales. Regarding belief about locus of control over health, God as a determining factor was given the highest endorsement. Mothers in the congenital cardiovascular malformations group reported a higher level of parental locus of control than did those in the control group. The correlations between stress and locus of control were stronger in the control than in the case group. Religiosity was related neither to stress nor to locus of control. Future studies can explore the roles that personal, familial, and societal factors play in exacerbating or reducing stress levels among parents of sick children, particularly in developing countries where economic pressures are acute.

Viral transmission risk factors in an Egyptian population with high hepatitis C prevalence.

BACKGROUND: Egypt has the world's highest prevalence of infection with hepatitis C virus (HCV), which is a major cause of hepatocellular carcinoma. The high HCV prevalence is largely attributed to the parenteral antischistosomal therapy (PAT) campaigns conducted from the 1950s through the 1980s; however, the primary modes of transmission in the post-PAT period are not well known. In this study we examined the associations between HCV prevalence and exposures to risk factors, including PAT, in a high HCV prevalence population. METHODS: Using a cross-sectional design, we examined the associations between demographic characteristics and risk factors for HCV transmission and HCV positivity prevalence among a sample of Egyptian residents. Data were collected through an interview-administered survey, and the association estimates were determined using χ (2) and logistic regression. RESULTS: The highest HCV positivity prevalence was observed in cohorts born before 1960, and declined precipitously thereafter; whereas the proportion of subjects reporting PAT remained relatively stable. Being male, having a rural residence, and having received PAT were all associated with HCV positivity; however, PAT alone could not account for the high prevalence of HCV. CONCLUSIONS: In Egypt, PAT and other transmission factors yet to be identified, as well as cohorts born before the 1960s and infected with HCV, are most likely the main contributors to the current HCV endemic.

Preventing hepatocellular carcinoma in Egypt: results of a Pilot Health Education Intervention Study.

BACKGROUND: Hepatocellular carcinoma (HCC), one of the most fatal malignancies, is particularly prevalent in Egypt, where we previously found deficiencies in knowledge concerning HCC and its risk factors. Hepatitis B and C viral infections are highly prevalent in Egypt, pesticides are very commonly used, and diets are often contaminated by aflatoxin, especially in rural areas. METHODS: We conducted a study to pilot test a health education intervention addressing HCC, its risk factors, and its main modes of prevention. It included four health education modules: HCC, hepatitis viruses, pesticides and aflatoxin. We used a pre- and post-intervention set of questionnaires to assess knowledge gained by the participants. RESULTS: A total of 25 participants from a village in the Nile Delta area attended the health education session and completed the questionnaires. The education intervention significantly increased the participants' knowledge on HCC and its risk factors, particularly regarding the use of pesticides at home and aflatoxin contaminated foods (both p < 0.05). Overall, there was a 12% increase in the number of participants who believed that HCC could be prevented, and they reported their intention to practice prevention for HCC risk factors. CONCLUSIONS: We found that the education intervention we pilot tested was feasible and proved effective in increasing participants' knowledge. Future efforts should focus on implementing targeted education programs in high-risk populations in Egypt.

Hepatitis C Virus (HCV) Vertical Transmission in 12-Month-Old Infants Born to HCV-Infected Women and Assessment of Maternal Risk Factors.

Background. Hepatitis C virus (HCV) is an underappreciated cause of pediatric liver disease, most frequently acquired by vertical transmission (VT). Current guidelines that include the option of screening infants for HCV RNA at 1-2 months are based on data prior to current real-time polymerase chain reaction (PCR)-based testing. Previous studies have demonstrated VT rates of 4%-15% and an association with high maternal viral load. We evaluated HCV RNA in infants with HCV VT and assessed maternal risk factors in a prospective cohort in Cairo, Egypt. Methods. Pregnant women were screened for HCV from December 2012 to March 2014. For those with HCV viremia, their infants were tested at 12 months for HCV RNA using real-time PCR. Maternal risk factors assessed for HCV VT association included HCV RNA levels, mode of delivery, and maternal IL28B genotype. Results. Of 2514 women screened, a total of 54 women were viremic (2.1%) and delivered 56 infants. Of those, 51 infants of 49 women were tested at 12 months of age. Only 7 infants were viremic, with an HCV VT rate of 14.3% (7 of 49). Median HCV RNA in the infants was 2100 IU/mL. None of the maternal risk factors analyzed were associated with transmission. Conclusions. In Egypt where HCV is highly endemic, we observed an overall 12-month HCV VT rate of 14.3%. Further studies should focus on better identification of pregnant women more likely to vertically transmit HCV and earlier testing of infants to identify those likely to develop chronicity.

Substance use by Egyptian youth: current patterns and potential avenues for prevention.

BACKGROUND: Substance abuse in Egypt is a serious public health threat. Recent studies have demonstrated increases in the prevalence of the use of tobacco, illegal drugs, and over-the-counter drugs, particularly among youth. METHODS: We conducted focus groups with a total of 40 male and female youth participants, ages 12-14 and 15-18, recruited from two different areas (Cairo and Alexandria) in 2012. We investigated their knowledge and perceptions regarding current substance use, its sources, and promoting and protecting factors, broadly addressing the use of tobacco products, illicit and prescription drugs, inhaled substances such as glue and solvents, and alcohol. RESULTS: Our findings suggest that: (1) youth in Egypt had access to and were actively using substances encountered in similar research worldwide, including tobacco, alcohol, illicit drugs, glue sniffing, and pharmaceutical agents; (2) smoking cigarettes and using hashish were the most common practices, and Tramadol was the most commonly used pharmaceutical drug; (3) peer pressure from friends stood out as the most common reason to start and continue using substances, followed by adverse life events and having a parent or family member who used substances; (4) strict parenting, religiosity, and having non-user friends were among the factors perceived by youth to prevent substance use or help them quit using substances; (5) most youths were aware of the adverse health effects of substance use. CONCLUSION: These findings will inform the design of quantitative surveys aimed at estimating the prevalence of specific behaviors related to substance use among youth and potential avenues for prevention.

Reliability of risk-based screening for hepatitis C virus infection among pregnant women in Egypt.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) only recommends risk-based HCV screening for pregnant women in the United States. This study sought to determine the reliability of risk-based versus universal HCV screening for pregnant women in Egypt, a country with the world's highest HCV prevalence that also relies on risk-based screening, and to identify additional characteristics that could increase the reliability of risk-based screening. METHODS: Pregnant women attending the Cairo University antenatal clinic were tested for anti-HCV antibodies and RNA, and demographic characteristics and risk factors for infection were assessed. RESULTS: All 1250 pregnant women approached agreed to participate (100%) with a mean age of 27.4 ± 5.5 years (range:16-45). HCV antibodies and RNA were positive in 52 (4.2%) and 30 (2.4%) women respectively. After adjustment, only age (OR:1.08, 95%CI:1.002-1.16, p < 0.01), history of prior pregnancies (OR:1.20, 95%CI:1.01-1.43, p < 0.04), and working in the healthcare sector (OR:8.68, 95%CI:1.72-43.62, p < 0.01), remained significantly associated with chronic HCV infection. CONCLUSIONS: Universal antenatal HCV screening was widely accepted (100%) and traditional risk-based screening alone would have missed 3 (10%) chronically infected women, thereby supporting universal screening of pregnant women whenever possible. Otherwise, risk-based screening should be modified to include history of prior pregnancy and healthcare employment.

Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers.

This study examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H: quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. Logistic regression was used to analyze data from a multicenter case-control study and estimate adjusted odds ratio (OR) and 95% confidence interval (CI). Exposure to pesticides was associated with increased bladder cancer risk (odds ratio (95% confidence interval): 1.68 (1.23-2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79 (1.25-2.56)) than for squamous cell (1.55 (1.03-2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19-3.85)) activities as compared with those with high NQO1 and low SOD2 genotypes (1.53 (0.73-3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism.

Applicability and efficacy of a model for prevention of perinatal transmission of hepatitis B virus infection: single center study in Egypt.

AIM: To identify possible maternal risk factors for hepatitis B virus (HBV) acquisition and assess the efficacy of immunoprophylaxis given to infants born to hepatitis B virus surface antigen (HBsAg) positive mothers. METHODS: Screening of 2000 pregnant females was carried out using rapid test and confirmed by enzyme immunoassay. A questionnaire consisting of 20 questions about the possible risk factors for acquisition of HBV infection was filled for every pregnant HBsAg positive female in addition to at least 2 pregnant HBsAg negative females for each positive case. Infants of HBsAg positive women were offered passive and active immunoprophylaxis within the 1st 48 h after birth, in addition to 2nd and 3rd doses of HBV vaccine after 1 and 6 mo respectively. Infants were tested for HBsAg and hepatitis B surface antibodies (HBsAb) at six months of age. RESULTS: HBsAg was confirmed positive in 1.2% of tested pregnant women. Risk factors significantly associated with HBV positivity were; history of injections (OR = 5.65), history of seeking medical advice in a clinic (OR = 7.02), history of hospitalization (OR = 6.82), history of surgery (OR = 4) and family history of hepatitis (OR = 3.89) (P < 0.05). Dropout rate was 28% for HBsAg women whose rapid test was not confirmed and could not be reached to provide immunoprophylaxis for thier newborns. Immunoprophylaxis failure was detected in only one newborn (3.7%) who tested positive for HBsAg at 6 mo of age; and vaccine failure (seronegative to HBsAb after 4 doses of the vaccine) was detected in another one (3.7%). The success rate of the immunoprophylaxis regimen was 92.6%. CONCLUSION: This pilot study shows that a successful national program for prevention of perinatal transmission of HBV needs to be preceded by an awareness campaign to avoid a high dropout rate.

Knowledge and perceptions of hepatitis C infection and pesticides use in two rural villages in Egypt.

BACKGROUND: Hepatocellular carcinoma (HCC), one of the most fatal types of malignancy, is increasing worldwide, and particularly in Egypt where there is a confluence of its contributing factors, including high prevalence of hepatitis C virus (HCV) infection, widespread use of pesticides, and diets that are contaminated by aflatoxin B1 (AFB1) in rural areas. We investigated knowledge, attitudes, and prevention practices related to HCV infection and pesticides use in rural Egypt, where over half of the population resides and agriculture is the predominant occupation. METHODS: From two rural villages we recruited 67 residents aged 18-80 years, who completed a 40-item survey that included questions about demographics, knowledge of and protective measures relevant to pesticides use in the home and in agriculture, awareness and perceptions of HCV infection and its treatment and prevention. RESULTS: Among the 67 study participants, gender distribution was equal, the mean age was 47.2, and one third never attended school. More than 50% reported using pesticides at home, but fewer reported having some knowledge about its health effects. Twelve participants were agricultural workers, and 11 of them applied pesticides in the field and knew about their toxicity; however only one person was correctly using the appropriate protective equipment. Among all the participants, 52 did not know what causes HCV infection, and 42 of those who knew it was a virus mentioned incorrect modes of transmission; and 30 did not know the disease manifestations. CONCLUSION: In rural Egypt, there is a significant lack of knowledge of HCV infection and its transmission mode and limited use of protective measures against pesticides despite familiarity with these chemicals.

Association of interferon-γ inducible protein-10 pretreatment level and sustained virological response in HCV-positive Egyptian patients.

BACKGROUND: The response to antiviral therapy in HCV infected patients depends on several predictive factors; however, the ability to achieve sustained virological response is still limited to around 60% of the patients infected with the HCV-4 genotype. Increased serum and intrahepatic interferon -γ inducible protein 10 (IP-10) levels in patients with chronic hepatitis C have been described. The aim of the work was to study the impact of pretreatment serum IP-10 level on the antiviral treatment outcome in a group of Egyptian patients infected with HCV. MATERIALS AND METHODS: The study included 80 treatment naive HCV patients. Serum IP-10 levels were determined by an enzyme linked immunosorbent assay before therapy was introduced. Serum samples were examined twice by Real-Time PCR after complete course of therapy for detection of HCV RNA; at the end of the antiviral therapy and six months later to detect sustained virological response (SVR). RESULTS: 57 patients (71%) achieved SVR while 23 (29%) patients were non-responders (NR). Pretreatment serum IP-10 levels were significantly lower in patients who achieved SVR than in NR (p=0.000). CONCLUSION: Low pretreatment serum IP-10 is a favorable predictive of response to antiviral HCV therapy in Egyptian patients.

Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt.

BACKGROUND: Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H: quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer. METHODS: We assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%. RESULTS: Water pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86-10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97-6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21-5.84]) than among the former (OR [CI 95%] = 1.86 [1.33-2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32-8.38]). CONCLUSION: Our findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection.

Agricultural workers and urinary bladder cancer risk in Egypt.

The authors examined the associations between farming and the risk for squamous cell (SCC) or urothelial cell (UC) carcinoma of the urinary bladder among Egyptians. The authors used data from a multicenter case-control study (1,525 male and 315 female cases, and 2,069 male and 547 female age- and residence-matched, population-based controls) to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Men in farming and who never smoked had increased risk for either SCC or UC (AOR [95% CI]: 4.65 [2.59-8.36] and 6.22 [3.82-10.15], respectively). If they ever smoked, their risks were 2.27 (1.75-2.95) and 1.93 (1.58-2.35), respectively. Women in farmer households were at increased risk for SCC (1.40 [0.93-2.09] and UC [1.25 (0.82-1.89]), although not statistically significant. Occupational and environmental exposures to farming increased the risk for bladder cancer among Egyptians.

Adipokines and insulin resistance, predictors of response to therapy in Egyptian patients with chronic hepatitis C virus genotype 4.

BACKGROUND: Hepatitis C virus (HCV) infection has major health impact worldwide and is a significant cause of chronic liver disease. In Egypt, HCV is highly endemic (up to 15% of the population); 91% of the patients are infected with genotype 4. Searching for new predictors of response to therapy is mandatory to decrease the cost and the adverse effects of current therapy. AIM: The aim of this study was to clarify the usefulness of serum leptin, adiponectin, and insulin resistance (IR) as predictors of response to treatment in hepatitis C virus genotype 4 (HCVG4). METHODS: One hundred patients with chronic HCVG4 who were candidates for treatment with pegylated interferon α and ribavirin were included in the study. Age, sex, and BMI were determined, and quantitative HCV PCR, assessment of serum leptin, adiponectin, IR, and pretreatment liver profile, and liver biopsy were performed. RESULTS: The male to female ratio was 68/32; the mean age of the patients was 40.9 ± 7.8 years and BMI was 28.3 ± 10 kg/m. Sustained virological response (SVR) was achieved by 56% of the patients. On performing logistic regression, BMI [odds ratio (OR) 6.5; P=0.004], serum leptin (OR 27.8; P ≤ 0.001), aspartate aminotransferase (OR 1.06; P ≤ 0.001), IR (OR 1.15; P ≤ 0.001), histological activity index (OR 1.77; P=0.006), and fibrosis (OR 2.93; P=0.001) were found to be independent negative predictors of SVR, whereas serum adiponectin (OR 0.74; P ≤ 0.001) was found to be an independent positive predictor of SVR. Pretreatment adiponectin (cutoff 13.75; sensitivity 92.86%; specificity 86.86%) shows area under the curve of 0.879 (95% confidence interval 0.802-0.956; P<0.001) and insignificant area under the curve for leptin or IR. CONCLUSION: BMI, pretreatment high leptin levels, and IR are negative predictors for SVR and pretreatment low adiponectin levels are an independent positive predictor for SVR in HCVG4.

Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt.

OBJECTIVES: To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men. MATERIALS AND METHODS: We used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively. RESULTS: The study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n = 169), and 527 controls. The odds of having either type of bladder cancer were lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0.34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women. CONCLUSIONS: These findings suggest that even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared with women in South Egypt.

Urinary bladder cancer risk factors in Egypt: a multicenter case-control study.

BACKGROUND: We investigated associations between tobacco exposure, history of schistosomiasis, and bladder cancer risk in Egypt. METHODS: We analyzed data from a case-control study (1,886 newly diagnosed and histologically confirmed cases and 2,716 age-, gender-, and residence-matched, population-based controls). Using logistic regression, we estimated the covariate-adjusted ORs and 95% confidence interval (CI) of the associations. RESULTS: Among men, cigarette smoking was associated with an increased risk of urothelial carcinoma (OR = 1.8; 95% CI, 1.4-2.2) but not squamous cell carcinoma (SCC); smoking both water pipes and cigarettes was associated with an even greater risk for urothelial carcinoma (OR = 2.9; 95% CI, 2.1-3.9) and a statistically significant risk for SCC (OR = 1.8; 95% CI, 1.2-2.6). Among nonsmoking men and women, environmental tobacco smoke exposure was associated with an increased risk of urothelial carcinoma. History of schistosomiasis was associated with increased risk of both urothelial carcinoma (OR = 1.9; 95% CI, 1.2-2.9) and SCC (OR = 1.9; 95% CI, 1.2-3.0) in women and to a lesser extent (OR = 1.4; 95% CI, 1.2-1.7 and OR = 1.4; 95% CI, 1.1-1.7, for urothelial carcinoma and SCC, respectively) in men. CONCLUSIONS: The results suggest that schistosomiasis and tobacco smoking increase the risk of both SCC and urothelial carcinoma. IMPACT: This study provides new evidence for associations between bladder cancer subtypes and schistosomiasis and suggests that smoking both cigarettes and water pipes increases the risk for SCC and urothelial carcinoma in Egyptian men.

GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt.

BACKGROUND: Bladder cancer is the most common male malignancy in Egypt, consists predominantly of urothelial cell carcinoma (UCC) and squamous cell carcinoma (SCC), and disparities in incidence exist between men and women regardless of geographic region. Tobacco smoke exposure and Schistosoma haematobium (SH) infection and the presence of GSTM1, GSTT1, and GPX1 genotypes, as modulators of the carcinogenic effect of reactive oxidative species, were hypothesized to modify bladder cancer risk and possibly explain these gender differences. METHODS: We evaluated the association between bladder cancer risk and functional polymorphisms in the GSTM1, GSTT1, and GPX1 genes in 625 cases and 626 matched population-based controls in Egypt and assessed for potential interactions between these candidate genes and environmental exposures, such as smoking and SH infection. We analyzed the risk for developing UCC and SCC separately. RESULTS: None of these functional polymorphisms were significantly associated with bladder cancer risk. There were no significant interactions between genotypes and smoking or SH infection in this population, nor was any difference detected in genotypic risk between men and women. CONCLUSIONS: Our findings suggest that common genetic variations in GSTM1, GSTT1, and GPX1 are not associated with bladder cancer risk overall and that well-known environmental risk factors, such as smoking and SH infection, do not interact with these genes to modulate the risk. IMPACT: Our data indicate that common genetic variations in GSTM1, GSTT1, and GPX1 were not associated with bladder cancer risk.