Determinants of early-onset colorectal cancer: a multicenter case-control study in Iran.

BACKGROUND: We aimed to study the risk factors of early-onset colorectal cancer (CRC) incidence in the Iranian population. Early onset CRC in Iran is a relevant health issue that deserves further epidemiological efforts to be defined and controlled as far as possible. Early age screening of low-tract of the intestine would be particularly useful in families of colorectal cancer patients. METHODS: We analyzed data from a multicenter hospital-based case-control study in Iran (The Iranian Study of Opium and Cancer). Sociodemographic and lifestyle information was collected using validated questionnaires. Multivariate logistic regressions estimated the odds ratios (OR) and 95% confidence intervals (CIs) for the association of early-onset CRC in individuals under the age of 50 and potential risk factors, including physical activity, socioeconomic status, body shape at age 15, dietary factors, vitamin D, cigarettes and waterpipe smoking, opium use and family history of CRC. Additionally, a subgroup analysis was conducted for individuals with a very young age of CRC onset (i.e. <35 years). RESULTS: We analyzed data of 189 developed CRC below age 50 (99 colon and 90 rectum), and 66 patients under the age 35 (13 colon and 21 rectum). Early CRC was inversely associated with vegetables (OR, 0.59; 95% CI, 0.38-0.92 for 422-576 g/day) and vitamin D (OR, 0.49; 95% CI, 0.26-0.94), and positively associated with red meat intake (OR, 1.80; 1.15-2.83 per 25.65 g/day). Vegetables (OR, 0.51; 95% CI, 0.27-0.98 for 576 g/day), red meat (OR, 2.05; 95% CI, 1.11-3.79 for 25.65 g/day), vitamin D (OR, 0.29; 95% CI, 0.10-0.86) and opium use (OR, 2.61; 95% CI, 1.01-6.74) were associated with early rectum cancer. Results were heterogeneous by cancer site for high fruit and vegetables intakes and cigarette smoking. Family history was associated with CRC (OR, 3.16; 95% CI, 1.29-10.9) and rectum cancer (OR, 3.22; 95% CI, 1.24-14.4) in subjects younger than 35, and, to a lesser extent, with CRC and rectum cancer before age 50. CONCLUSION: Early-onset CRC was related to the intake of vegetables, vitamin D and red meat in Iran. Early-onset rectum cancer was associated with regular opium use. Family history was associated with early CRC and early rectum cancer, particularly below the age of 35.

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.

Role of dietary intake of specific polyunsaturated fatty acids (PUFAs) on colorectal cancer risk in Iran.

High-fat diets have been associated with colorectal cancer (CRC) risk, and the role of polyunsaturated fatty acids (PUFAs) has been reported to vary based on the length of PUFAs. We explored the association between dietary omega-6 and omega-3 PUFAs intake and CRC. We analyzed 865 CRC patients and 3206 controls from a case-control study of Iran (IROPICAN study). We used multivariate logistic regression models to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the association between PUFAs intake and CRC risk. Our results showed that gamma-linolenic acid (18:3 n-6, GLA), arachidonic acid (20:4n-6, ARA), a-linolenic acid (Cis-18:3n-3, ALA), eicosapentaenoic acid (20:5n-3, EPA), docosahexaenoic acid (22:6n-3, DHA) consumption was not associated with the risk of CRC. However, the OR of linoleic acid (18: 2n-6, LA) intake was 1.47 (95% CI 1.01-2.14, p = 0.04) for proximal colon and that of docosapentaenoic acid (22:5n-3, DPA) intake was 1.33 (95% CI 1.05-1.69, p = 0.01) for rectum. This study indicates a high level of LA is associated with an increased risk of proximal colon cancer, and DPA intake was positively associated with rectum cancer risk. Furthermore, our study noted a high intake of n-6 (from vegetable oils) compared to n-3 PUFAs (from fish and seafood) in this population. Public awareness and government support is needed to increase fish and seafood production and consumption in Iran.

Determinants of waterpipe smoking in Iranian adults: results from the IROPICAN study.

Introduction: Waterpipe smoking has become increasingly popular in Western countries, particularly among young individuals. This study aims to identify the factors influencing waterpipe smoking by focusing on consumption patterns. Methods: We utilized data from a multicenter case-control study (IROPICAN) conducted in Iran. Multivariate logistic regression estimated the adjusted odds ratio and 95% confidence intervals as a measure of association between waterpipe smoking and different factors. Results: Among 3,477 subjects were included, 11.8% were waterpipe smokers. Most of <50 years old smokers were occasional (80%), while daily smokers were often >50 years (85%). Around 59% of occasional users started it before 30 years old. Low education, low SES, alcohol consumption, cigarette smoking, secondhand smoke exposure, and opium use were associated with waterpipe smoking. Stratified analysis by frequency pattern showed an association between occasional smoking with age 0.97 (0.96-0.98), university degree 0.36 (0.17-0.76), urban dwellers 1.40 (1.06-1.86) and between high SES and daily smoking 0.34 (0.17-0.69). Conclusion: Our results offer valuable information to policymakers for developing waterpipe smoking control measures. The occasional waterpipe smoking results may be generalized to the younger people in Western countries.

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.

Dietary total antioxidant capacity and head and neck cancer: a large case-control study in Iran.

Background: Data on the association between head and neck cancer (HNC) and dietary factors are inconclusive. No study has so far investigated the association between dietary total antioxidant capacity (dTAC) and HNC concerning interactions with other risk factors. Method: Pathologically confirmed new diagnosed HNC patients were included in this study. The control group was healthy hospital visitors who were frequently matched with patients on age (5 years interval), gender, and province of residence. Trained interviewers administered a validated Food Frequency Questionnaire (FFQ) to assess the participants' food intake 1 year before the cancer diagnosis. Data on TAC scores of foods was collected by Ferric Reducing Antioxidant Power (FRAP) and Total Radical-trapping Antioxidant Parameters (TRAP) from published data. We applied logistic regression adjusted for age, sex, energy intake, socioeconomic status, province, opium use, alcohol use, physical activity, and dental health. We also studied the interaction of dTAC with tobacco smoking status, and opium use on the risk of HNC. Results: We recruited 876 HNC patients and 3,409 healthy controls. We observed a significant decrease in the odds of HNC with increasing dTAC scores. The OR of HNC for the third vs. the first tertile was 0.49 (95%CI 0.39-0.61) for FRAP and 0.49 (95%CI 0.39-0.62) for TRAP. Both dTAC scores were inversely associated with lip and oral (T3 ver. T1 OR = 0.51; 95%CI 0.36-0.71 for FRAP and OR = 0.59; 95% CI 0.44-0.82 for TRAP) and larynx (T3 ver. T1 OR = 0.43; 95%CI 0.31-0.61 for FRAP and OR = 0.38; 95% CI 0.26-0.55 for TRAP) cancers. There was no interaction between tobacco smoking, opium use; and TRAP or FRAP on the risk of HNC. Conclusion: An antioxidant-rich diet in terms of FRAP or TRAP could decrease the risk of HNC and its subtypes.

Bladder cancer risk in relation to occupations held in a nationwide case-control study in Iran.

Globally, bladder cancer has been identified as one of the most frequent occupational cancers, but our understanding of occupational bladder cancer risk in Iran is less advanced. This study aimed to assess the risk of bladder cancer in relation to occupation in Iran. We used the IROPICAN case-control study data including 717 incident cases and 3477 controls. We assessed the risk of bladder cancer in relation to ever working in major groups of the International Standard Classification of Occupations (ISCO-68) while controlling for cigarette smoking, opium consumption. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). In men, decreased ORs for bladder cancer were observed in administrative and managerial workers (OR 0.4; CI: 0.2, 0.9), and clerks (OR 0.6; CI: 0.4, 0.9). Elevated ORs were observed in metal processors (OR 5.4; CI: 1.3, 23.4), and workers in occupations with likely exposure to aromatic amines (OR 2.2; CI: 1.2, 4.0). There was no evidence of interactions between working in aromatic amines-exposed occupations and tobacco smoking or opium use. Elevated risk of bladder cancer in men in metal processors and workers likely exposed to aromatic amines aligns with associations observed outside Iran. Other previously confirmed associations between high-risk occupations and bladder cancer were not observed, possibly due to small numbers or lack of details on exposure. Future epidemiological studies in Iran would benefit from the development of exposure assessment tools such as job exposure matrices, generally applicable for retrospective exposure assessment in epidemiological studies.

Dietary Choline and Betaine Intake and Risk of Colorectal Cancer in an Iranian Population.

BACKGROUND: Colorectal cancer (CRC) is increasing in low- and middle-income countries, likely due to changing lifestyle habits, including diet. We aimed to investigate the relationship between dietary betaine, choline, and choline-containing compounds and CRC risk. METHODS: We analyzed data from a case-control study, including 865 CRC cases and 3206 controls from Iran. Detailed information was collected by trained interviewers using validated questionnaires. The intake of free choline, phosphocholine (Pcho), glycerophosphocholine (GPC), phosphatidylcholine (PtdCho), and sphingomyelin (SM), as well as of betaine was estimated from food frequency questionnaires and categorized into quartiles. The odds ratios (OR) and 95% confidence intervals (CI) of CRC for choline and betaine quartiles were calculated using multivariate logistic regression by adjusting for potential confounders. RESULTS: We observed excess risk of CRC in the highest versus lowest intake of total choline (OR = 1.23, 95% CI 1.13, 1.33), GPC (OR = 1.13, 95% CI 1.00, 1.27), and SM (OR = 1.14, 95% CI 1.01, 1.28). The intake of betaine exerted an inverse association with CRC risk (OR = 0.91, 95% CI 0.83, 0.99). There was no association between free choline, Pcho, PtdCho, and CRC. Analyses stratified by gender showed an elevated OR of CRC in men for SM intake OR = 1.20, 95% CI 1.03, 1.40) and a significantly decreased CRC risk in women for betaine intake (OR = 0.84, 95% CI 0.73, 0.97). CONCLUSION: Dietary modifications leading to an increase in betaine sources and managing the use of animal products as references for SM or other choline types might contribute to decreasing the risk of CRC.

Direct and indirect medical costs of bladder cancer in Iran.

BACKGROUND: Bladder cancer is one of the most prevalent and costly cancers in the world. Estimating the economic burden of bladder cancer is essential for allocating resources to different sectors of health systems and determining the appropriate payment mechanisms. The present study aimed at estimating the economic burden of bladder cancer in Iran. METHODS: In this study, we used a prevalence-based approach for estimating the economic burden of bladder cancer. Direct and indirect costs of bladder cancer were calculated using the cost of illness and human capital approaches. Data were collected using a researcher-made checklist obtained from several sources including Iran bladder cancer clinical practice guideline, the Statistical Center of Iran, Iran's Ministry of Cooperatives, Labor, and Social Welfare, Relative Value of Health Services (RVHS) book and Iranian Food and Drug Administration organization. The analyses were done by Microsoft Excel 2013 and Stata 13. RESULTS: The number of the cases of 5-year prevalence of bladder cancer in Iran was estimated as 21,807 people in 2018. The economic burden of bladder cancer in Iran was estimated at US$ 86,695,474. Indirect medical costs constituted about two-third of the economic burden of bladder cancer, and mostly related to productivity loss due to mortality. Most of the direct medical costs (29.7%) were related to the stage T2-T3 and transurethral resection of bladder (31.01%) and radical cystectomy (19.99%) procedures. CONCLUSION: Our results showed that the costs of bladder cancer, imposed on the healthcare system, were significant and mostly related to lost production costs. The implementation of screening and diagnostic programs can improve the survival rate and quality of life of patients and reduce the cost of lost productivity due to mortality in these patients.

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.

Association between dietary fat intake and colorectal cancer: A multicenter case-control study in Iran.

The evolving trends in colorectal cancer (CRC) as one of the most common malignancies worldwide, have likely been influenced by the implementation of screening programs and changes in lifestyle habits. Changing lifestyle, including the shift in diet composition with higher fat, sugar, and animal-source foods intake, led to an increasing burden of CRC in countries undergoing rapid socioeconomic improvement. Results for the link between specific fatty acids (FAs) and CRC are generally inconclusive and more limited in developing countries than elsewhere. This study aims to investigate the association between FA intakes and CRC and its anatomical subsites in a large Iranian case-control study. A food frequency questionnaire was used to collect information on dietary intake in 865 cases and 3206 controls. We conducted multivariate logistic regression models to calculate the odds ratio (OR) and 95% confidence interval (CI). We found positive association between CRC and high intake of dietary total fat (OR highest quartile Q4 = 1.77, 95% CI = 1.32-2.38), cholesterol (ORQ4 = 1.58, 95% CI = 1.22-2.05), and palmitoleic acid (ORQ4 = 2.16, 95% CI = 1.19, 3.91), and an inverse association with high intake of dietary heptanoic acid (ORQ4 = 0.33, 95% CI = 0.14, 0.79) and low intake of palmitic acid (OR lowest quartile Q2 = 0.53, 95% CI = 0.31-0.88). None of the fat variables were associated with rectal cancer. Our study suggests that the recommendation of limited consumption of fats may decrease the risk of CRC among the Iranian population.

Dietary Ruminant and Industrial Trans-Fatty Acids Intake and Colorectal Cancer Risk.

As colorectal cancer (CRC) is largely due to modifiable lifestyle habits, the awareness on its risk factors is highly important. Dietary fatty acids have been linked to CRC risk. We explored the association between dietary trans fatty acids (TFAs) intake and CRC risk. We analyzed 865 CRC cases (434 in colon and 404 in rectum) and 3206 controls of the IROPICAN study, with data collected by trained interviewers using validated questionnaires. TFAs intake (industrial and ruminant types) was categorized into quartiles. Multivariate logistic regression models were built to calculate the odds ratios (OR) for the association between CRC and TFAs. We observed a positive association between industrial TFAs and colon cancer (OR for highest vs lowest quartile [ORQ4vsQ1] = 1.28, 95% confidence interval 1.07-1.54). A higher association was observed between industrial TFAs and CRC, occurring after 50 years of age. In addition, elaidic acid was associated with an increased risk of colon (ORQ4vsQ1 = 1.58, 1.24-2.02) and specifically of proximal colon cancer (OR Q4vsQ1 = 2.12, 1.40-3.20), as well as of rectum cancer (ORQ4vsQ1 = 1.40, 1.07-1.83). An inverse association was observed between ruminant TFAs intake and colon cancer risk (ORQ4vsQ1 = 0.80, 0.67-0.97). Industrial TFAs, such as semisolid/solid hydrogenated oils, may increase the risk of CRC, especially colon and proximal colon cancer. In contrast, ruminant TFAs do not appear to be associated with CRC. Awareness programs and regulatory actions regarding hydrogenated oils are warranted, given their high consumption through ultra-processed foods in more developed and less developed countries.

Lung cancer risk in relation to jobs held in a nationwide case-control study in Iran.

BACKGROUND: Globally, lung cancer is the most frequent occupational cancer, but the risk associated with the occupations or occupational environment in Iran is not clear. We aimed to assess occupations with the risk of lung cancer. METHODS: We used the IROPICAN nationwide case-control study data including 658 incident lung cancer cases and 3477 controls. We assessed the risk of lung cancer in relation to ever working in major groups of International Standard Classification of Occupations, high-risk occupations for lung cancer and duration of employment and lung cancer subtype among construction workers and farmers while controlling for cigarette smoking and opium consumption. We used unconditional regression logistic models to estimate ORs for the association between increased lung cancer risk and occupations. RESULTS: We observed elevated ORs for lung cancer in male construction workers (OR=1.4; 95% CI: 1.0 to 1.8), petroleum industry workers (OR=3.2; 95% CI: 1.1 to 9.8), female farmers (OR=2.6; 95% CI: 1.3 to 5.3) and female bakers (OR=5.5; 95% CI: 1.0 to 29.8). A positive trend by the duration of employment was observed for male construction workers (p< 0.001). Increased risk of squamous cell carcinoma was observed in male construction workers (OR=1.9; 95% CI: 1.2 to 3.0) and female farmers (OR=4.3; 95% CI: 1.1 to 17.2), who also experienced an increased risk of adenocarcinoma (OR=3.8; 95% CI: 1.4 to 9.9). DISCUSSION: Although we observed associations between some occupations and lung cancer consistent with the literature, further studies with larger samples focusing on exposures are needed to better understand the occupational lung cancer burden in Iran.

Estimating the Prevalence of Bladder Cancer by Stage in Iran as a Developing Country.

Background: Bladder cancer is among the 10 most common cancers globally and in Iran. The prevalence rate is a crucial metric for both estimating disease burden and policymakers. On the other hand, bladder cancer is a heterogeneous disease with different stages, high recurrence, and progression rate. In planning treatment procedures, it is important to know the prevalence of bladder cancer by stages. In the current study, we aimed to estimate the 5-year prevalence of bladder cancer by stages using the Markov model. Methods: This was a simulation study. To estimate the 5-year prevalence of bladder cancer by stages, we used the Markov model with a time horizon of 5 years following diagnosis. We simulated the natural history of bladder cancer using a literature review. We extracted survival rate, stage-specific recurrence, and progression rate using local and international publications and expert opinion. In addition, we used the Iranian life table and extracted probabilities of mortality due to other causes of death. Results: Five-year prevalence of bladder cancer for the year 2018 was estimated at 21,807 patients. Non- muscle-invasive bladder cancer accounted for around 68% of all cases, with 42% in the Ta low-grade stage. About 32% of bladder cancer prevalent cases were muscle-invasive bladder cancer patients, from which about 8% had metastatic tumors. Conclusion: Researchers and policymakers can utilize the findings of this study to conduct economic burden analyses and plan resource allocation.

Consumption of Yoghurt and Other Dairy Products and Risk of Colorectal Cancer in Iran: The IROPICAN Study.

BACKGROUND: There is evidence of an inverse association between yoghurt intake and risk of colorectal cancer (CRC). We aimed at investigating the association between the intake of yoghurt and other dairy foods consumed in Iran and CRC risk. METHODS: Our analysis included 4070 subjects within the IROPICAN (Iran Study of Opium and Cancer) study. Detailed information was collected by the use of validated questionnaires. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between the intake of total dairy products, and, separately, of yoghurt, milk, cheese, kashk, dough, cream, ice cream, and other milk products, and CRC using unconditional logistic regression analyses. The intake was categorized in tertiles. RESULTS: Overall, we analyzed 865 cases and 3205 controls. Total dairy products intake was not associated with CRC. The OR for one tertile increase (OR_T) in yoghurt intake was 0.97 (95% CI 0.87-1.08) for CRC and 0.66 (95% CI 0.52-0.84) for proximal colon cancer. Cream intake was associated with CRC (OR_T3 = 1.33, 95% CI 1.08-1.64), colon (OR_T3 = 1.37, 95% CI 1.03-1.81), and proximal cancer (OR_T3 = 1.29, 95% CI 1.04-1.61). The OR of distal colon cancer for ice cream intake was 0.59 (95% CI 0.43-0.82). Other dairy products were not associated with CRC risk.

Human Papillomavirus and Risk of Head and Neck Squamous Cell Carcinoma in Iran.

Human papillomavirus (HPV) causes a subset of head and neck squamous cell carcinoma (HNSCC). Knowledge of determinants of α-, ß-, and γ-HPVs types in the oral cavity is required for a better understanding of HNSCC development. Oral rinse samples of 498 HNSCC cases and 242 controls from the IROPICAN study-a large multicenter case-control study in Iran-were screened for 21 α-HPV, 46 ß-HPVs, and 52 γ-HPVs using bead-based HPV genotyping assays. α-HPVs were detected only in 1.2% of the patients and 2.9% of the controls from which HPV16 was the most prevalent type among participants. ß-HPVs were detected in 43.8% of the patients and 38.6% of the controls where the lip and oral cavity (45.5%) had the highest positivity. Values for γ-HPV prevalence in patients and controls were 26.1% and 24.7%, respectively. The highest percentage of γ-HPV positivity was found in the larynx (30.4%). Concerning the ß genus, HPV23 and HPV38 were the most prevalent types among the patients and controls, respectively. For the γ genus, SD2 in cases and HPV134 in controls were the most prevalent types. Overall, detection of α-HPVs (aOR, 0.40; 95% CI = 0.1 to 1.2; P = 0.11), ß-HPVs (aOR, 1.9; 95% CI = 0.9 to 1.6; P = 0.29), and γ-HPVs infections (aOR, 1.04; 95% CI = 0.7 to 1.5; P = 0.83) was not associated with the HNSCC development. Our data did not suggest an HPV-related etiology for HNSCC pathogenesis. Nonetheless, this study provides novel insights into the diversity of ß-, and γ-HPVs in different HNSCC anatomical subsites. IMPORTANCE Infection with human papillomavirus (HPV) is responsible for a subset of neck squamous cell carcinoma (HNSCC), but knowledge of the prevalence of and risk factors for oral HPV infection, especially cutaneous types in Iran, remains unknown. In a large retrospective study, the authors used a sensitive assay for the detection of α-, ß-, and γ-HPVs in oral rinse samples of HNSCC and matched controls. They find that the α-HPV contribution to HNSCC in Iran is lower than global prevalence. High-risk α-HPVs or cutaneous ß- and γ-HPVs were not associated with the HNSCC development. Besides, this study provides novel insights into the diversity of ß- and γ-HPVs in different HNSCC anatomical subsites.

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

BACKGROUND: Bladder cancer (BC) is the 10th most common type of cancer worldwide and the fourth most common type of cancer in Iran. Opium use is considered as one of the risk factors for BC. We aim to assess the association between various parameters of opium use, which in Iran is mainly ingested or smoked in various forms, and the risk of BC. METHOD: In this multi-centre case-referent study in Iran, 717 BC cases and 3477 referents were recruited to the study from May 2017 until July 2020. Detailed histories of opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure adjusted odds ratio (OR) and 95% confidence intervals (CI). The ORs were adjusted for age, gender, place of residence and pack-years of cigarette smoking. RESULTS: Regular opium consumption was associated with an increased risk of BC (OR 3.5, 95% CI: 2.8, 4.3) compared with subjects who never used opium. Compared with continuous users, the risk decreased to one-third for those who stopped opium more than 10 years ago. The adjusted OR for those who used both crude opium (teriak) and opium juice was 7.4 (95% CI: 4.1, 13.3). There was a joint effect of opium and tobacco (OR for users of both opium and tobacco 7.7, 95% CI: 6.0, 9.7). CONCLUSIONS: Regular opium use is associated with an approximately 4-fold risk for BC. The OR decreases along with the increasing time since stopping opium use.

Correction: Sensitivity of self-reported opioid use in case-control studies: Healthy individuals versus hospitalized patients.

[This corrects the article DOI: 10.1371/journal.pone.0183017.].

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.

The Iranian Study of Opium and Cancer (IROPICAN): Rationale, Design, and Initial Findings.

BACKGROUND: The International Agency for Research on Cancer (IARC) recently classified opium use as a Group 1 carcinogen. However, much remains to be studied on the relation between opium and cancer. We designed the Iranian Opium and Cancer (IROPICAN) study to further investigate the association of opium use and cancers of the head and neck, bladder, lung, and colon and rectum. In this paper, we describe the rationale, design, and some initial results of the IROPICAN Study. METHODS: The IROPICAN is a multi-center case-control study conducted in 10 provinces of Iran. The cases were all histologically confirmed and the controls were selected from hospital visitors who were free of cancer, were not family members or friends of the cancer patients, and were visiting the hospital for reasons other than their own ailment. The questionnaires included detailed questions on opium use (including age at initiation, duration, frequency, typical amount, and route), and potential confounders, such as tobacco use (e.g., cigarettes, nass and water-pipe), and dietary factors. Biological samples, including blood and saliva, were also collected. RESULTS: The validation and pilot phases showed reasonably good validity, with sensitivities of 70% and 69% for the cases and controls, respectively, in reporting opium use. The results also showed excellent reliability, with intra-class correlation coefficients of 0.96 for ever opium use and 0.88 (95% CI: 0.80, 0.92) for regular opium use. In the main phase, we recruited 3299 cancer cases (99% response rate) and 3477 hospital visitor controls (89% response rate). The proportion of ever-use of opium was 40% among cases and 18% among controls. CONCLUSION: The IROPICAN study will serve as a major resource in studies addressing the effect of opium on risk of cancers of the head and neck, bladder, lung, and colon and rectum.