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.

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.

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.

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.

Substitution of dietary macronutrients and their sources in association with breast cancer: results from a large-scale case-control study.

PURPOSE: To evaluate the association between dietary replacement of carbohydrates, proteins, fats, and their sources and odds of developing breast cancer (BC). METHODS: This hospital-based large-scale case-control study recruited 464 women with confirmed BC within the past year and 500 apparently healthy controls matched in terms of age and residential place. Dietary data as well as other variables were collected by trained interviewers. RESULTS: After adjustment for all possible confounders, substituting every 50 kcal of energy from dietary carbohydrates for the same amount of energy from total fats was associated with lower odds for developing BC among all participants [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95-0.99] as well as premenopausal women (OR 0.96, 95% CI 0.94-0.99). Replacing protein intake with fat was associated with a higher likelihood of BC among postmenopausal women (OR 1.11, 95% CI 1.03-1.20). Replacement of carbohydrates with MUFAs might be associated with a decreased odds of BC and replacement of dietary carbohydrates with PUFAs might be associated with an increased odds of BC in all participants as well as postmenopausal women (P < 0.05). The same association was shown for protein only in postmenopausal women. Substituting MUFAs for saturated (SFAs) and PUFAs was associated with a significant decreased odds of BC in the whole population (P < 0.05). The same association was observed for replacing MUFAs for PUFAs in postmenopausal women. CONCLUSION: Substitution of dietary carbohydrates for total fats and PUFAs might reduce the odds of breast cancer. Also, substituting MUFAs for carbohydrates, SFAs and PUFAs might lower the disease risk. Future prospective investigations are highly recommended.

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.

Does Opium Consumption Have Shared Impact on Atherosclerotic Cardiovascular Disease and Cancer?

Although atherosclerotic cardiovascular disease (ASCVD) and cancer are seemingly different types of disease, they have multiple shared underlying mechanisms and lifestyle-related risk factors like smoking, unhealthy diet, excessive alcohol consumption, and inadequate physical activity. Opium abuse is prevalent in developing countries, especially the Middle East region and many Asian countries. Besides recreational purposes, many people use opium based on a traditional belief that opium consumption may confer protection against heart attack and improve the control of the risk factors of ASCVD such as diabetes mellitus, hypertension, and dyslipidemia. However, scientific reports indicate an increased risk of ASCVD and poor control of ASCVD risk factors among opium abusers compared with nonusers. Moreover, there is accumulating evidence that opium consumption exerts potential carcinogenic effects and increases the risk of developing various types of cancer. We conducted a review of the literature to review the current evidence on the relationship between opium consumption and ASCVD as well as various kinds of cancer. In addition, we will discuss the potential shared pathophysiologic mechanisms underlying the association between opium abuse and both ASCVD and cancer.

Association between dietary fat and fat subtypes with the risk of breast cancer in an Iranian population: a case-control study.

AIM: To examine the relationship between dietary fat intake and breast cancer (BC) development. METHOD: This case-control study included 473 women with breast cancer (pathologically confirmed) and 501 healthy subjects matched by age and residency. Dietary intakes of different types and sources of fatty acids were assessed using a validated food frequency questionnaire. The association between dietary fats and odds of BC was assessed using a logistic regression model in crude and multivariable-adjusted models. P values below 0.05 were regarded as statistically significant. RESULTS: Participants' age and body mass index were 44.0 ± 10.8 years and 28.4 ± 5.6 kg/m2, respectively. Individuals with the highest quartile of total fat intake and polyunsaturated fatty acid (PUFA) intake were 1.50 times more at risk to develop BC than others. A positive significant association was observed between animal fat (Q4 vs. Q1, OR = 1.89, 95 % CI = 0.93-3.81), saturated fatty acid (SFA) (Q4 vs. Q1, OR = 1.70, 95 % CI = 0.88-3.30), monounsaturated fatty acid (MUFA) (Q4 vs. Q1 OR = 1.85, 95 % CI = 0.95-3.61) and PUFA intake (Q4 vs. Q1, OR = 2.12, 95 % CI = 1.05-4.27) with BC risk in postmenopausal women. However, there was no association in premenopausal women. CONCLUSIONS: Total dietary fat and its subtypes might increase the risk of BC, especially in postmenopausal women. This observational study confirms the role of dietary fat in breast cancer development. Intervention studies involving different estrogen receptor subgroups are needed.

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.

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.

Gene Panel Testing in Hereditary Breast Cancer.

BACKGROUND: Breast cancer (BC) is a highly complex, heterogeneous and multifactorial disease and is the most commonly diagnosed cancer and the leading cause of cancer-related mortality in women worldwide. Family history and genetic mutations are important risk factors for BC. While studies in twins have estimated that about 10%-30% of BC are due to hereditary factors, only 4%-5% of them are due to mutations in BRCA1 or BRCA2 genes. Our aim was to investigate the role of other BC genes in familial BC among the Iranian population. METHODS: We selected 61 BC patients who were wild-type for BRCA1 and BRCA2 mutations but who met the criteria for hereditary BC based on the American College of Medical Genetics and Genomics (ACMG) and the National Comprehensive Cancer Network (NCCN) guidelines. We performed targeted sequencing covering the exons of 130 known cancer susceptibility genes based on the Cancer Gene Census list. RESULTS: We found seven mutations in seven known BC susceptibility genes (RAD50, PTEN, TP53, POLH, DKC1, WRN and CHEK2) in seven patients including two pathogenic frameshift variants in RAD50 and WRN genes, four pathogenic missense variants in TP53, PTEN, POLH, and DKC1 genes and a pathogenic splice donor variant in the CHEK2 gene. The presence of all these variants was confirmed by Sanger sequencing and Gap reverse transcription-polymerase chain reaction (RT-PCR) for the splice variant. In silico analysis of all of these variants predicted them to be pathogenic. CONCLUSION: Panel testing of BC patients who met the established criteria for hereditary BC but who were negative for BRCA1/2 mutations provided additional relevant clinical information for approximately 11.5% of the families. Our findings indicate that next generation sequencing (NGS) is a powerful tool to investigative putative mutagenic variants among patients who meet the criteria for hereditary BC, but with negative results on BRCA1/2 testing.

An Exploratory Study of Units of Reporting Opium Usein Iran: Implications for Epidemiologic Studies.

BACKGROUND: Measuring the amount of opium use is a challenge in epidemiologic studies. Self-report of amount of opium use at each consumption, widely used in the literature, usually fails to provide a good estimate. The purpose of this study is to systematically study the perceived weight units of reported opium use in Iran, and compare them to the standardized units of weight measurement. METHODS: An exploratory descriptive study was conducted in six major cities of Iran. Study participants were interviewed and asked to use a Play-Doh-like material to demonstrate the amount of opium they use. To obtain an estimate of the weight of the material used, we multiplied the volume by the density of the opium product. We experimentally determined the density of the commonly used opium products. We used medians and inter-quartile ranges (IQRs) to report the typical amount of each unit. RESULTS: A total of 108 individuals participated in this study. The most frequently reported unit was "gram"; the median perceived weight for one gram (g) of opium was 0.24 (IQR: 0.16) g. The second most commonly used unit was nokhod with a median of 0.16 (IQR: 0.16) g, followed by mesghaal and hab/habeh, which were 1.28 (IQR: 0.81) and 0.16 (IQR: 0.16) g, respectively. The median perceived weight of mesghaal and gram in the studied cities was less than the expected standardized values. CONCLUSION: In conclusion, the reported amount of opium use is highly inaccurate and unreliable, and is mainly subject to underestimation.

Travel Burden and Clinical Profile of Cancer Patients Admitted to the Cancer Institute of Iran in 2012.

BACKGROUND: Burden of cancer is increasing in developing countries, where healthcare infrastructures and resources are limited. Evaluating the pattern of care would provide evidence for planning and improvement of the situation. MATERIALS AND METHODS: We studied the pattern of residential place and clinical information of cancer patients who were admitted to the Cancer Institute of Iran from January 1, to May 31, 2012. RESULTS: We studied 1,705 consecutive cancer patients admitted to the Cancer Institute in the study period. The most common cancers were breast (29.2%), colorectal (9.0%), stomach (8.3%), head & neck (8.0%) and esophageal (3.8%) cancers. Radiotherapy was the main treatment (52.1%) followed by chemotherapy (43.8%) and surgery (29.1%). We found that 60% of the patients presented in the loco-regional or advanced stages. About 35% of patients travelled from other provinces mainly from Mazandaran (13.4%), Lorestan (10.6%), Zanjan (7.8%) and Ghazvin (6.6%). On average, the cancer patients travelled about 455 kilometers to receive care in the cancer institute. We found more than 38% patients who were referred from other provinces had an early stage tumor. CONCLUSION: Establishment of comprehensive cancer centers in different geographical regions and implementation of a proper referral system for advanced cancer patients is needed to improve the patient outcomes and mitigate the burden of travel of patients for cancer care.

Situation analysis of the National Comprehensive Cancer Control Program (2013) in the I. R. of Iran; assessment and recommendations based on the IAEA imPACT mission.

INTRODUCTION: Iran was engaged in the Program of Action for Cancer Therapy (PACT) in 2012, and delegates from the International Atomic Energy Agency (IAEA), and the World Health Organization (WHO) evaluated the National Cancer Control Program (NCCP) status (the imPACT mission), based on which they provided recommendations for improvements of NCCP in the I.R. of Iran. We reported the results of this situational analysis and discussed the recommendations and their implication in the promotion of NCCP in the I.R. of Iran.  METHODS: International delegates visited the I.R. of Iran and evaluated different aspects and capacities of NCCP in Iran. In addition, a Farsi version of the WHO/IAEA self-assessment tool was completed by local experts and stakeholders, including experts from different departments of the Ministry of Health and Medical Education (MOHME) and representatives from the National Cancer Research Network (NCRN). Following these evaluations, the PACT office provided recommendations for improving the NCCP in Iran. Almost all the recommendations were endorsed by MOHME. RESULTS: The PACT program provided 31 recommendations for improvement of NCCP in Iran in six categories, including planning, cancer registration and information, prevention, early detection, diagnosis and treatment, and palliative care. The most important recommendation was to establish a strong, multi-sectoral NCCP committee and develop an updated national cancer control program. CONCLUSION: The imPACT mission report provided a comprehensive view about the NCCP status in Iran. An appropriate response to these recommendations and filing the observed gaps will improve the NCCP status in the I.R. of Iran.