Association of opium use and tobacco smoking with α-, ß-, and γ-human papillomavirus oral infection.

Head and neck squamous cell carcinomas (HNSCCs) are linked to tobacco smoking, opium use, and human papillomavirus (HPV) infection. However, little is known about the association of HPV infection with risk factors of HNSCCs, including opium and tobacco use. This cross-sectional analysis of a national multi-center case-control study in Iran included 498 HNSCC cases and 242 controls. We investigated the association of opium and tobacco use with α- (n = 21), ß- (n = 46), and γ-HPV (n = 52) types in saliva samples using type-specific bead-based multiplex genotyping assays (TS-MPG). We found that α-HPV positivity was significantly associated with tobacco smoking (OR = 10.35; 95% CI = 1.15, 93; p = .03), but not with opium use (OR = 1.06; 95% CI = 0.41, 2.76; p = .89). Additionally, tobacco smoking correlated with an elevated risk of ß-species 2 HPV infection (OR = 1.28; 95% CI = 1.04, 1.58; p = .020). Conversely, opium use showed a positive association with γ-species 12 HPV infection (OR = 5.67; 95% CI = 1.43, 22.44; p = .013). These findings indicate that tobacco and opium use may influence the risk of HPV infection in different ways depending on the HPV genus and species. Further studies are needed to replicate these findings in other populations.

Population attributable proportion and number of cancer cases attributed to potentially modifiable risk factors in Iran in 2020.

In the current study, we aimed to calculate the fraction of cancer attributable to modifiable risk factors in Iran in 2020. Population attributable fractions (PAFs) were calculated for established cancer risk factors using three data sources: the national cancer incidence reports, relative risks extracted from global and national meta-analyses, and exposure prevalence from national/subnational population-based surveys. In addition to overall cancers, the PAFs were estimated separately for each cancer site among men and women. Overall, 32.6% of cancers in 2020 in Iran were attributable to known risk factors. The PAF in men (40.2%) was twice as high as in women (21.1%). Cigarette smoking (15.4%), being overweight (5.0%), opium use (3.9%) and H. pylori infection (3.8%) were the leading causes of cancers. For men, the highest PAFs belonged to cigarette smoking (26.3%), opium use (6.8%) and being overweight (3.1%), while for women, the highest PAFs belonged to being overweight (7.2%), H. pylori infection (2.7%) and cigarette smoking (2.7%). Among Iranian men and women, the PAFs of waterpipe smoking were 2% and 0.9%, respectively. A third of incident cancers in Iran are due to modifiable exposures, mainly cigarette smoking, being overweight, and H. pylori infection. Opium consumption and waterpipe smoking collectively accounted for 8.8% of cancer occurrence in men and 1.3% in women in Iran. These emerging risk factors should be taken into consideration in future PAF studies.

Opium use and risk of lung cancer: A multicenter case-control study in Iran.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.

Opium use and risk of colorectal cancer: a multi-center case-referent study in Iran.

BACKGROUND: Opium use has been associated with an increased risk of cancers of the lung, oesophagus, and pancreas, and it was recently classified by the International Agency for Cancer Research as carcinogenic to humans. It is not clear whether opium also increases the risk of colorectal cancer (CRC). The aim of our study was to assess the association between various metrics of opium use and the risk of CRC. METHODS: This case-referent study from seven provinces in Iran comprised 848 CRC cases and 3215 referents. Data on opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure odds ratios (OR) adjusted for age, gender, province, marital status, family history of CRC-linked cancers, consumption of red meat, fruits and vegetables, body shape, occupational physical activity, and socioeconomic status. RESULTS: Regular opium consumption was not associated with the risk of CRC (OR 0.9, 95% confidence interval, CI: 0.7, 1.2) compared to subjects who never used opium. However, frequent opium use more than twice a day was associated with an increased risk of CRC compared to non-users of opium (OR: 2.0, 95% CI: 1.1, 3.8; p for quadratic trend 0.008). CONCLUSION: There seems to be no overall association between opium use and CRC, but the risk of CRC might be increased among persons who use opium many times a day.

Geographic distribution and time trends of water-pipe use among Iranian youth and teenage students: A meta-analysis and systematic review.

Water-pipe tobacco smoking is harmful to health, yet its rate of prevalence remains uncertain. Recent evidence has shown that the prevalence of water-pipe smoking among students is higher than in the general population. In this study, a systematic review of related literature on water-pipe use was conducted, and for this purpose, 76 articles were examined in the study. In this vein, geographic distribution and time trends of water-pipe consumption in Iran were considered. The results of this study showed that lifetime, last-year, and last-month prevalence of water-pipe smoking use among Iranian students were 28.78 (25.07-32.49), 20.84 (16.01-25.66), and 16.36 (11.86-20.85), respectively. The results also showed a wide variation by the region and sex in Iran. This study has shown the importance of addressing public prevention and alerting programs in schools and universities.

The Impact of Socioeconomic Inequality on Mental Health among Adolescents in Qazvin, Iran: Blinder-Oaxaca Decomposition Method.

Background: Mental health is integral to public health in adolescents. Although previous studies have shown that low socioeconomic status (SES) is associated with mental disorders (MD), it is unclear which mental health domains are most important. Thus, our study aimed to investigate the associations between 5 domains of mental disorder and SES inequality in adolescents. Methods: We conducted a cross-sectional study among adolescents (N = 1724). Associations between SES inequality with mental disorders, such as emotional symptoms, conduct problems, hyperactivity, peer relationship problems, and prosocial behavior, were examined. We used the concentration index (CI) to determine inequality. The gap between the low and high socioeconomic groups was decomposed into its determinants using the Blinder-Oaxaca decomposition method. Results: Mental health's overall CI was -0.085 (P ˂ 0.001). The emotional problem was primarily caused by SES inequality (-0.094 [P = 0.004]). Decomposition of the gap between the 2 economic groups showed that physical activity, school performance, exercise, parents' smoking status, and gender were the most important determinants of inequality. Conclusion: SES inequality plays a vital role in adolescents' mental health. It seems that the emotional problem domain of mental health might be more amenable to interventions than other domains.

National surveillance of cancer survival in Iran (IRANCANSURV): Analysis of data of 15 cancer sites from nine population-based cancer registries.

Cancer survival is a key indicator for the national cancer control programs. However, survival data in the East Mediterranean region (EMR) are limited. We designed a national cancer survival study based on population-based cancer registries (PBCRs) from nine provinces in Iran. The current study reports 5-year net survival of 15 cancers in Iranian adults (15-99 years) during 2014 to 2015 in nine provinces of Iran. We used data linkages between the cancer registries and the causes of death registry and vital statistics and active follow-up approaches to ascertain the vital status of the patients. Five-year net survival was estimated through the relative survival analysis. We applied the international cancer survival standard weights for age standardization. Five-year survival was highest for prostate cancer (74.9%, 95% CI 73.0, 76.8), followed by breast (74.4%, 95% CI 72.50, 76.3), bladder (70.4%, 95% CI 69.0, 71.8) and cervix (65.2%, 95% CI 60.5, 69.6). Survival was below 25% for cancers of the pancreas, lung, liver, stomach and esophagus. Iranian cancer patients experience a relatively poor prognosis as compared to those in high-income countries. Implementation of early detection programs and improving the quality of care are required to improve the cancer survival among Iranian patients. Further studies are needed to monitor the outcomes of cancer patients in Iran and other EMR countries.

Opium use and the risk of head and neck squamous cell carcinoma.

Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case-control study-Iran Opium and Cancer study, we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx and 28 other subsites within the head and neck) and 3065 frequency-matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95% confidence intervals (95% CIs) were obtained using mixed-effects logistic regression because of heterogeneity among centers. The adjusted OR (95% CI) for regular opium use was 3.76 (2.96-4.79) for all HNSCC combined. Strong dose-response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx and other subsites within the head and neck with OR (95% CI) of 2.90 (1.40-6.02), 6.55 (4.69-9.13) and 5.95 (2.41-14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20-10.74). For the first time, the current study showed opium users have an increased risk of several anatomic subsites of HNSCC.

Dietary N-nitroso compounds intake and bladder cancer risk: A systematic review and meta-analysis.

Bladder cancer is the most common cancer of the urinary tract. While tobacco smoking is responsible for more than half of the bladder cancer cases, occupational exposures is also an established risk factor of bladder cancer. Strong evidence of carcinogenicity of N-nitroso compounds (NOCs) have been provided in animal and human studies, but the target organ of occurring cancer in human including bladder cancer is still obscure. A wide range of NOCs sources surrounded us like diet, drinking water, cigarette smoking, workplace, and indoor air population. We conducted a meta-analysis to elucidate the association between NOCs in drinking water and food source and bladder cancer risk. Ten articles were included after removing the duplicates and irrelevant articles. The majority studies of our meta-analysis was done on women, maybe because of cigarette smoking as a main risk factor among men which is more common among men than women. Although the number of articles was limited our meta-analysis showed no significant association between dietary intakes of NOCs and bladder cancer risk (OR = 0.96, 95% CI = 0.88, 1.05; I2 = 50%, P-value = 0.007), neither subgrouping of NOCS type and source of NOCs nor dose of nitrate and nitrite intake indicated any associations.

Dietary carbohydrate quality and risk of breast cancer among women.

BACKGROUND: A few studies have examined the relationship between carbohydrate quality index (CQI) and risk of breast cancer (BC) among women in Middle Eastern countries. We studied the associations between carbohydrate quality index and the risk of BC in overall and by menopausal status. METHODS: In this case-control study, dietary intake of 461 women with pathologically confirmed BC within the past year were examined. The same information were collected for 495 apparently healthy controls using a 168-item validated FFQ. Carbohydrate quality was determined by considering four criteria including: ratio of solid carbohydrates to total carbohydrates, dietary fiber intake, GI and the ratio of whole grains to total grains. RESULTS: Mean GI and GL of participants were totally 57.5 ± 7.2 and 245.7 ± 64.7, respectively. A trend toward significant association was seen between GI and odds of BC in the whole population; such that after stratifying analysis by menopausal status, premenopausal women in the highest quartile of GI were 1.85 times higher likely to have BC than those in the lowest quartile (95% CI: 1.12, 3.07, P = 0.01). We found that women with the greatest CQI had lower odds for BC, compared with those with the lowest CQI (0.63; 95% CI: 0.43-0.94, P = 0.03). This association was remained after stratifying analysis by menopausal status in premenopausal (0.55; 95% CI: 0.34-0.90, P = 0.04). CONCLUSION: We found that GI was directly and CQI inversely associated with odds of BC. In order to determine the effects of dietary carbohydrate quality prospective cohort studies are needed.

Opium use reporting error in case-control studies: neighborhood controls versus hospital visitor controls.

Background: There are relatively scant data to determine whether hospital visitors could serve as a proper source of controls in case-control studies of illicit drug use. The aim of this study was to evaluate using neighborhood versus hospital visitor controls in reporting opium use. Methods: We used data from 2 independent case-control studies of cancer in Iran. In the first study, controls were selected from neighborhoods of the patients. For the second one, controls were selected from among hospital visitors. In the latter study, hospital visitors were companions of the patients or others visiting the hospital for reasons other than disease treatment. We used stata (version 12; Stata Corp( for all analyses and with a significance level of 0.05. Results: Data from 616 of neighborhood controls and 414 of hospital visitor controls were analyzed. Opium point prevalence among men was significantly higher in hospital visitors than neighborhood controls (43.3% vs 32.2%; P = 0.047), while the prevalence of cigarette smoking was very similar in both control groups (46.3% vs 47.2%; P =.847). Using a logistic regression analysis, in an unadjusted analysis, neighborhood controls were less likely to report opium use in both genders, with (unadjusted OR = 0.77; 95% CI: 0.59,1). After adjusting for potential confounders, the differences of opium use between the 2 control groups became more pronounced (Adjusted OR = 0.26; 95% CI: 0.10, 0.69). Conclusion: Because of the similarity of reporting cigarette smoking among neighborhood controls but substantially lower reporting of opium use among them, we concluded that neighborhood controls underreport opium use-a sensitive question- and that using neighborhood control biases the findings in case-control studies. Hospital visitor controls may be more appropriate than neighborhood controls for case-control studies of illicit drugs.

Occult hepatitis C virus infection in patients with beta-thalassemia major: Is it a neglected and unexplained phenomenon?

Occult hepatitis C virus (HCV) infection (OCI) is described as the presence of viral genome in both hepatocytes and peripheral blood mononuclear cells (PBMCs) despite constant negative results on serum HCV RNA tests. Beta-thalassemia major (BTM) describes a group of inherited blood diseases. Patients with BTM require repeated blood transfusions, increasing the risk of exposure to infectious agents. We aimed to assess the prevalence of OCI in Iranian BTM patients and to identify the role of host factors in OCI positivity. A total of 181 BTM patients with HCV negative markers were selected. HCV RNA was tested in PBMCs using nested polymerase chain reaction assay. The positive samples were then genotyped via restriction fragment-length polymorphism (RFLP) and 5'-untranslated region sequencing. Six (3.3%) out of 181 BTM patients had viral HCV genomes in PBMC samples. Three (50.0%), two (33.3%), and one (16.7%) out of these six patients were infected with HCV-1b, HCV-1a, and HCV-3a, respectively. OCI positivity was significantly associated with the serum level of uric acid (P = 0.045) and ABO blood group (P = 0.032). Also, OCI patients had unfavorable IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ∆G/∆G genotypes. In conclusion, we indicated the low frequency of OCI in BTM patients. Nevertheless, more attention is warranted considering the importance of this infection. Also, further studies are necessary to determine the actual prevalence of OCI among BTM patients in Iran.

Low viral load of Merkel cell polyomavirus in Iranian patients with head and neck squamous cell carcinoma: Is it clinically important?

Recent studies show that the human Merkel cell polyomavirus (MCPyV) may be involved in causing cancer. The objective of this study was to assess the impact of MCPyV on the development of head and neck squamous cell carcinoma (HNSCC). In total, 50 paraffin-embedded HNSCC biopsy samples and 50 adjacent non-cancerous samples were evaluated for the presence of MCPyV DNA and RNA. Among patients, the five most frequent histopathologic sites were the tongue (22.0%), lip (16.0%), submandibular (14.0%), cheek (14.0%), and throat (14.0%). MCPyV DNA was positive in eight (16.0%) samples. The median MCPyV LT-Ag copy number in the eight positive samples and in one non-cancerous sample was 4.8 × 10-3 and 2.6 × 10-5 copies/cell, respectively. Quantification of MCPyV LT-Ag revealed increased expression in stage III (5.6 × 10-3 copies/cell) than in the other stages. The MCPyV DNA load in different stages of HNSCC was also statistically significant (P = 0.027). The viral load was low, suggesting that only a fraction of cancerous cells is infected. This result provides evidence confirming the presence of MCPyV in a subset of Iranian patients with HNSCCs, but further studies needed to confirm our findings.

Systematic review of priority setting studies in health research in the Islamic Republic of Iran.

BACKGROUND: Several research priority-setting studies have been conducted in different countries, including the Islamic Republic of Iran. AIMS: We conducted a systematic review and evaluated the quality of the priority-setting reports about health research in the Islamic Republic of Iran. METHODS: English and Farsi databases were searched from January to July 2016 to extract reports (up to December 2015) about priority setting in health research in the Islamic Republic of Iran. We constructed a checklist to extract data from the identified studies. Articles were studied in detail and content analysis was carried out. Relevant items were scored and analysed using Microsoft Excel. RESULTS: We identified 36 articles. Eight articles involved all the main stakeholders. About half the articles used valid criteria for ranking. Transparency was fulfilled in 13 articles. Upstream rules and regulations were ignored in 26 articles. An implementation plan was considered in 9 articles and context analysis was demonstrated in only 3. CONCLUSIONS: Developing standard packages for priority setting, training of researchers and improving the capacity of organizations may improve the quality of priority-setting studies in the future.

Potential impact of controlling opium use prevalence on future cancer incidence in Iran.

Background: The International Agency for Research on Cancer (IARC) recently classified opium consumption as carcinogenic to humans. This study aimed to estimate the potential reduction in incident cancers by 2035 in Iran, which accounts for 42% of global opium consumption, through decreasing opium use prevalence. Methods: The population attributable fraction (PAF) of opium-related cancers was projected using national cancer incidence, age- and gender-specific opium use prevalence, relative cancer risks associated with opium use, and annual percentage changes in cancer incidence rates in Iran. Opium-related cancers were defined based on IARC monographs as cancers of lung, larynx, bladder, esophagus, stomach, pancreas, and pharynx. The number of preventable cancer cases under different opium prevalence scenarios was determined by subtracting attributable cases in each year based on current prevalence from those in alternative scenarios. Findings: By 2035, an estimated 3,001,421 new cancer cases are expected in Iran, with 904,013 (30.1%) occurring in opium-related sites. Maintaining the current opium prevalence (5.6%) is projected to cause 111,130 new cancer cases (3.7% of all cancers, 12.3% of opium-related). A 10%, 30%, and 50% reduction in opium prevalence could prevent 9,016, 28,161, and 49,006 total incident cancers by 2035 in Iran, respectively. Reducing opium use prevalence by 10%-50% is projected to have the highest impact on lung cancer (prevention of 2,946-15,831 cases), stomach cancer (prevention of 2,404-12,593 cases), and bladder cancer (prevention of 1,725-9,520 cases). Interpretation: Our results highlight the significant benefits that can be achieved through effective cancer prevention policies targeting opium use in Iran. Neglecting this risk factor is estimated to pose a significant burden on cancer incidence in the next decade in this population. Funding: None.

Dietary Inflammatory Index and Head and Neck Cancer: A Multicenter Case-Control Study in Iran.

BACKGROUND: The inflammatory potential of diet may affect carcinogenesis. This study aimed to determine the association between dietary inflammatory index (DII) and the risk of head and neck cancer (HNC), as well as the interaction between DII and cigarette smoking in HNC development within the Iranian population. Study Design: This is a case-control study. METHODS: In this multicenter case-control study, participants' dietary intake was assessed using a validated 130-item food frequency questionnaire, from which DII was computed. The study recruited 876 new cases from referral hospitals across 10 provinces and 3409 healthy controls who were frequency-matched based on age, gender, and residential place. Logistic regression was used to obtain odds ratios (ORs) for HNC across tertiles of DII, which were adjusted for confounding variables. RESULTS: A higher pro-inflammatory diet was associated with an increased risk of all HNC (OR T3 vs. T1 [95% CI]: 1.31 [1.06, 1.62]; P-trend=0.013). There was a significant association between lip and oral cavity cancers and DII (OR T3 vs. T1 [95% CI]: 1.56 [1.16, 1.66]; P-trend=0.004). Furthermore, an inflammatory diet was associated with an increased risk of pharynx cancer (OR T3 vs. T1 [95% CI]: 2.08 [1.14, 3.79]; P-trend=0.02). Additionally, no significant association was observed between DII and larynx cancer, while an interaction was found between DII and tobacco use on the risk of HNC (OR T3 vs. T1 [95% CI]: 2.52 [1.78, 3.57]; P-interaction=0.03). CONCLUSION: DII was positively associated with HNC risk. There was a significant association between DII and the risk of lip, oral cavity, and pharynx cancers. Additionally, there was an interaction between tobacco use and DII in determining the risk of HNC.

Exposure to second-hand smoke and risk of lung cancer among Iranian population: A multicenter case-control study.

OBJECTIVE: Despite the implementation of the WHO Framework Convention on Tobacco Control (FCTC) program in Iran, the regulation of second-hand smoke (SHS) exposure-an often-overlooked hazard-, still requires improvement. We employed a multi-center case-control study to investigate the association between exposure to secondhand smoke (SHS) from various tobacco products (cigarettes, water-pipes, pipes, and chopogh), opium use, and the risk of lung cancer. METHOD: We included 627 lung cancer cases and 3477 controls. Exposure to SHS tobacco and SHS opium was collected through a questionnaire. We used mixed-model logistic regressions to estimate odds ratios (ORs) and 95% confidence intervals (CI). RESULT: Among the overall population exposed to second-hand tobacco smoke (SHTS), the odds ratio (OR) compared to those never exposed was 1.35 (95% CI: 1.08-1.71). Never smokers who were ever exposed to second-hand tobacco smoke (SHTS) had 1.69-fold risk of lung cancer compared to those who were never exposed (95% CI: 1.13-2.52). Exposure to SHTS between 2-3 per day (OR = 2.27, 95% CI: 1.13-4.53) and more than three hours per day (OR = 2.29, 95% CI: 1.20-4.37) can increase the risk of lung cancer compared with the no exposure group (P-trend <0.01). We did not observe any association between exposure to second-hand opium smoke (SHOS) and the risk of lung cancer, either in the overall population or among never-smokers. CONCLUSION: Our study estimates the impact of second-hand tobacco smoke (SHTS) on lung cancer risk in both the overall population and never-smokers. Additional studies are required to evaluate the association between exposure to second-hand smoke from opium and other type of tobacco, including water-pipe and the risk of lung cancer.

Allergies and risk of head and neck cancer: a case-control study.

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case-control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58-88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

Unveiling an Association between Waterpipe Smoking and Bladder Cancer Risk: A Multicenter Case-Control Study in Iran.

BACKGROUND: Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern. METHODS: We used the IROPICAN database in Iran and used multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer. RESULTS: We analyzed 717 cases and 3,477 controls and a subset of 215 patients and 2,145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 [95% confidence interval (CI), 0.69-1.20], we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR = 1.78; 95% CI, 1.16-2.72) compared with non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR = 2.25; 95% CI, 1.21-4.18) and for initiating waterpipe smoking at an age less than 20 (OR = 2.73; 95% CI, 1.11-6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR = 2.35; 95% CI, 1.24-4.42) than in current smokers (OR = 1.52; 95% CI, 0.72-3.15). All observed associations were consistently higher for urothelial histology. CONCLUSIONS: Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium. IMPACT: The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers. See related In the Spotlight, p. 461.

Association of Dietary Nitrate, Nitrite, and N-Nitroso Compounds Intake and Gastrointestinal Cancers: A Systematic Review and Meta-Analysis.

N-nitroso compounds (NOCs) are a class of chemical carcinogens found in various environmental sources such as food, drinking water, cigarette smoke, the work environment, and the indoor air population. We conducted a systematic review and meta-analysis to investigate the links between nitrate, nitrite, and NOCs in food and water and the risk of gastrointestinal (GI) cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC). A systematic search of the literature in Scopus, PubMed, Google Scholar, Web of Science, ScienceDirect, and Embase was performed for studies on the association between NOCs in drinking water and food sources and GI cancers. Forest plots of relative risk (RR) were constructed for all the cancer sites and the intake sources. The random-effects model was used to assess the heterogeneity between studies. Forty articles were included after removing duplicate and irrelevant articles. The meta-analysis indicated that the intake of high dose vs. low dose of these compounds was significantly associated with the overall GI cancer risk and nitrite (RR = 1.18, 95% CI = 1.07-1.29), and N-nitrosodimethylamine (NDMA) (RR = 1.32, 95% CI = 1.06-1.65). We found that dietary nitrite intake increased GC (RR = 1.33, 95% CI = 1.02-1.73), and EC (RR = 1.38, 95% CI = 1.01-1.89). Additionally, dietary NDMA intake increased the risk of CRC (RR = 1.36, 95% CI = 1.18-1.58). This meta-analysis provides some evidence that the intake of dietary and water nitrate, nitrite, and NOCs may be associated with GI cancers. In particular, dietary nitrite is linked to GC and EC risks and dietary NDMA intake is associated with CRC.