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Is Opium a Real Risk Factor for Esophageal Cancer or Just a Methodological Artifact? Hospital and Neighborhood Controls in Case-Control Studies

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Authors:
Ramin Shakeri at Tehran University of Medical Sciences
Ramin Shakeri
Farin Kamangar at Morgan State University
Farin Kamangar
Dariush Nasrollahzadeh
Dariush Nasrollahzadeh
Dariush Nasrollahzadeh
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Mehdi Nouraie at University of Pittsburgh
Mehdi Nouraie
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Abstract and Figures

Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC). We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age- and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age- and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17-2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63-1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure. Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.
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... A total of 106 studies were retained following the first screening of titles and abstracts and the exclusion of studies that were not relevant. Following a second screen of the full text of the manuscripts, 35 studies were included (one publication [41] included two studies). These 35 studies then underwent quality assessment and data abstraction. ...
... There were a total of six new case-control studies identified following the Monographs meeting [30,35,38,[42][43][44]. A total of 15 studies examined the association between opium consumption and bladder cancer (1 cohort and 14 case-control), 7 for laryngeal cancer (1 cohort and 6 case-control), 6 for oesophageal cancer (1 cohort and 4 case-control, one publication [41] describes two separate studies, with different sets of cases and controls), 5 for stomach cancer (2 cohort and 3 case-control), 5 for lung cancer (1 cohort and 4 case-control), and 4 for pancreatic cancer (1 cohort and 3 case-control). The studies included approximately 8400 cancer cases, of whom 2947 reported opium consumption (bladder cancer, n = 1091; oesophageal cancer, n = 295; laryngeal cancer, n = 545; lung cancer, n = 536; pancreatic cancer, n = 231; and stomach cancer, n = 249). ...
... Several case-control (n = at least 9) studies also used the GCS questionnaire (GCSQ) [7,31,32,34,35,37,41,52,55]. A similarly detailed questionnaire was also used in the IROPICAN study [38,42,43,52]. ...
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... Most researchers agree, there is no ideal control group in a case-control study, and researchers must carefully consider the representativeness of the control group, because a biased control group can lead to wrong results [39]. In this study, we selected hospital controls, despite the well-documented tendency for the use of hospital controls to weaken or obscure relationships [40,41] ,but the majority of our results remained statistically significant. ...
The Association between Allergy and Cancer: A Case-Control Study
Article
Full-text available
  • Aug 2024
Background: Allergies may either have a protective or a promoting effect on cancers. This study seeks to explore the relationship between various types of allergies and three specific cancer types: lung, breast, and colorectal cancer, thereby adding fresh insights to the existing scientific. Methods: Among the 556 patients, there were 115 cases of colorectal cancer, 305 cases of breast cancer, and 136 cases of lung cancer. The ratio of the case group to the control group was 1:1. We assessed the association between various variables, such as family history of allergy, allergies since the age of 10, pet allergies, seasonal flu, night and activity-related coughing, food allergies, itching or urticaria, childhood respiratory infections, and common colds, with the aforementioned cancers. The data were also analyzed using conditional logistic regression. Results: The results showed a protective association between itching or urticaria due to environmental factors and colorectal cancer (adjusted odds ratio [AOR]: 0.4, 95% CI: 0.17-0.94), as well as lung cancer (AOR: 0.26, 95% CI: 0.09-0.75). Additionally, a borderline association was observed between itching or urticaria and breast cancer (AOR: 0.54, 95% CI: 0.28-1.03). Allergy to pets also exhibited an inverse borderline association with breast cancer (AOR: 0.44, 95% CI: 0.18-1.05) and lung cancer (AOR: 0.25, 95% CI: 0.06-1.14). Furthermore, night coughing and allergies since the age of 10 were found to increase the odds of developing breast cancer (AOR: 2.38, 95% CI: 1.44-3.92; AOR: 5.10, 95% CI: 2.56-10.56, respectively) and lung cancer (AOR: 2.40, 95% CI: 1.29-4.46; AOR: 8.71, 95% CI: 3.29-23.03, respectively). Conclusion: allergies and cancer have a site-specific assciation . To confirm these findings and understand the reasons behind these associations, more investigation is required.
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... All digestive tract-related malignant diseases are considered gastrointestinal (GI) cancer which includes esophageal, pancreatic, gastric, hepatic, gallbladder and colorectal cancer [88]. In an epidemiological case-control study, Shakeri et al. [99] found that an emerging esophageal cancer cell carcinoma risk factor can be opium. To evaluate the association between opium use and cancer risk, the meta-analysis review of 21 observational studies, with a combined sample size of 64 412 individuals and 6658 cases of cancer was carried out by Mansouri et al. [13]. ...
Opium alkaloids, biosynthesis, pharmacology and association with cancer occurrence
Article
Full-text available
  • May 2023
Papaver somniferum L. (Family: Papaveraceae) is a species well known for its diverse alkaloids (100 different benzylisoquinoline alkaloids (BIAs)). L-tyrosine serves as a precursor of several specific metabolites like BIAs. It has been used as an antitussive and potent analgesic to alleviate mild to extreme pain since ancient times. The extraction of pharmaceutically important alkaloids like morphine and codeine from poppy plant reflects the need for the most suitable and standard methods. Several analytical and extraction techniques have been reported in open literature for morphine, codeine and other important alkaloids which play a vital function in drug development and drug discovery. Many studies suggest that opioids are also responsible for adverse effects or secondary complications like dependence and withdrawal. In recent years, opium consumption and addiction are the most important risk factors. Many evidence-based reviews suggest that opium consumption is directly linked or acts as a risk factor for different cancers. In this review, we highlight significant efforts related to research which have been done over the past 5 decades and the complete information on Papaver somniferum including its phytochemistry, pharmacological actions, biosynthetic pathways and analytical techniques of opium alkaloid extraction and the link between opium consumption and cancer-related updates.
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Opium use and gastrointestinal cancers: a systematic review and meta- analysis study
Article
Full-text available
  • Apr 2024
Aim: The current systematic review and meta-analysis aimed to assess the association between Gastrointestinal (GI) cancers and opium use. Background: GI malignancies are a global public health issue and are associated with many risk factors including genetic and lifestyle factors. Methods: PubMed, Web of Science, Embase and Scopus and the Google Scholar search engine in addition to Persian databases including Magiran and SID were searched using relevant keywords. The associations of opium use, long duration of opium use, high daily amount opium use and high cumulative opium use and GI cancer and various subtypes of GI cancers were estimated and pooled in format of odds ratios (OR) and their corresponding 95% confidence intervals (CI) with a random effects model. Results: 22 articles that were published between 1983 and 2022 entered the analyses. There were significant relationships between opium use based on crude effect sizes (OR: 2.53, 1.95-3.29) and adjusted effect sizes (OR: 2.64, 1.99-3.51), high daily opium use (or: 3.41, 1.92-6.06), long duration of opium use (OR: 3.03, 1.90-4.84) and high cumulative opium use (OR: 3.88, 2.35-6.41), all compared to never opium use, and GI cancer. The results were not sensitive to sensitivity analyses and no influential publication biases were found in these analyses. Conclusion: Our meta-analysis showed that opium use could be associated with increased risk of overall and some particular GI cancers including oropharyngeal, gastric, pancreatic and colorectal cancers. Opium use as a potentially modifiable factor, therefore, should be more emphasized.
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Opium use and gastrointestinal cancers: a systematic review and meta-analysis study
Article
Full-text available
  • Apr 2024
Aim: The current systematic review and meta-analysis aimed to assess the association between Gastrointestinal (GI) cancers and opium use. Background: GI malignancies are a global public health issue and are associated with many risk factors including genetic and lifestyle factors. Methods: PubMed, Web of Science, Embase and Scopus and the Google Scholar search engine in addition to Persian databases including Magiran and SID were searched using relevant keywords. The associations of opium use, long duration of opium use, high daily amount opium use and high cumulative opium use and GI cancer and various subtypes of GI cancers were estimated and pooled in format of odds ratios (OR) and their corresponding 95% confidence intervals (CI) with a random effects model. Results: 22 articles that were published between 1983 and 2022 entered the analyses. There were significant relationships between opium use based on crude effect sizes (OR: 2.53, 1.95-3.29) and adjusted effect sizes (OR: 2.64, 1.99-3.51), high daily opium use (or: 3.41, 1.92-6.06), long duration of opium use (OR: 3.03, 1.90-4.84) and high cumulative opium use (OR: 3.88, 2.35-6.41), all compared to never opium use, and GI cancer. The results were not sensitive to sensitivity analyses and no influential publication biases were found in these analyses. Conclusion: Our meta-analysis showed that opium use could be associated with increased risk of overall and some particular GI cancers including oropharyngeal, gastric, pancreatic and colorectal cancers. Opium use as a potentially modifiable factor, therefore, should be more emphasized. Keywords: Opium, Gastrointestinal tract, Cancer, Meta-analysis
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Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County
Article
Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.
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The carcinogenicity of opium consumption: a systematic review and meta-analysis
Article
Full-text available
  • Feb 2023
  • EUR J EPIDEMIOL
The carcinogenicity of opium consumption was recently evaluated by a Working Group convened by the International Agency for Research on Cancer (IARC). We supplement the recent IARC evaluation by conducting an extended systematic review as well as a quantitative meta-analytic assessment of the role of opium consumption and risk for selected cancers, evaluating in detail various aspects of study quality on meta-analytic findings. We searched the published literature to identify all relevant studies on opium consumption and risk of selected cancers in humans through 31 October, 2022. Meta-relative risks (mRRs) and associated 95% confidence intervals (CIs) were estimated using random-effects models for studies of cancer of the urinary bladder, larynx, lung, oesophagus, pancreas, and stomach. Heterogeneity among studies was assessed using the I2 statistic. We assessed study quality and conducted sensitivity analyses to evaluate the impact of potential reverse causation, protopathic bias, selection bias, information bias, and confounding. In total, 2 prospective cohort studies and 33 case–control studies were included. The overall pooled mRR estimated for ‘ever or regular’ versus ‘never’ use of opium ranged from 1.50 (95% CI 1.13–1.99, I2 = 0%, 6 studies) for oesophageal cancer to 7.97 (95% CI 4.79–13.3, I2 = 62%, 7 studies) for laryngeal cancer. Analyses of cumulative opium exposure suggested greater risk of cancer associated with higher opium consumption. Findings were robust in sensitivity analyses excluding studies prone to potential methodological sources of biases and confounding. Findings support an adverse association between opium consumption and cancers of the urinary bladder, larynx, lung, oesophagus, pancreas and stomach.
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Opium Use and the Risk of Liver Cancer: A Case-Control Study
Article
  • Sep 2022
Limited evidence is available to acknowledge the association between opium use and liver cancer. In a case–control study, we recruited 117 cases of primary liver cancer (PLC) and 234 age and sex-matched neighborhood controls from 2016 to 2018. We calculated odds ratios (OR) for opium use and 95% confidence intervals (95% CI), using conditional logistic regressions. Compared with non-users the adjusted OR (AOR, 95% CI) for opium use was 6.5 (95% CI, 2.87–13.44). Compared with people who had no history of use, a strong dose–response effect of opium use was observed by amount of use (AOR, 10.70; 95% CI, 3.92–28.70). Cumulative use of opium also indicated that using over 30 gr-year could increase the PLC risk dramatically (AOR, 11.0; 95% CI, 3.83–31.58). Those who used opium for more than 21 years were highly at risk of PLC (AOR, 11.66; 95% CI, 4.43–30.67). The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Prevention Relevance The results of this study indicate that opium use dramatically increased the risk of liver cancer. Because opioids are increasing for medical and non-medical use globally; accordingly, severe health consequences such as liver cancer have to be investigated widely.
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A Prospective Study of Tobacco, Alcohol, and the Risk of Esophageal and Gastric Cancer Subtypes
Article
Full-text available
  • Jun 2007
  • AM J EPIDEMIOL
Rates of esophageal adenocarcinoma and gastric cardia adenocarcinoma have increased, while rates of esophageal squamous cell carcinoma (ESCC) and gastric noncardia adenocarcinoma have decreased, suggesting distinct etiologies. The authors prospectively investigated the associations of alcohol and tobacco with these cancers in 474,606 US participants using Cox models adjusted for potential confounders. Between 1995/1996 and 2000, 97 incident cases of ESCC, 205 of esophageal adenocarcinoma, 188 of gastric cardia, and 187 of gastric noncardia cancer occurred. Compared with nonsmokers, current smokers were at increased risk for ESCC (hazard ratio (HR) = 9.27, 95% confidence interval (CI): 4.04, 21.29), esophageal adenocarcinoma (HR = 3.70, 95% CI: 2.20, 6.22), gastric cardia (HR = 2.86, 95% CI: 1.73, 4.70), and gastric noncardia (HR = 2.04, 95% CI: 1.32, 3.16). Assuming causality, ever smoking had population attributable risks of 77% (95% CI: 0.55, 0.89) for ESCC, 58% (95% CI: 0.38, 0.72) for esophageal adenocarcinoma, 47% (95% CI: 0.27, 0.63) for gastric cardia, and 19% (95% CI: 0.00, 0.37) for gastric noncardia. For drinkers of more than three alcoholic beverages per day, compared with those whose intake was up to one drink per day, the authors found significant associations between alcohol intake and ESCC risk (HR = 4.93, 95% CI: 2.69, 9.03) but not risk for esophageal, gastric cardia, or gastric noncardia adenocarcinoma.
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Tea drinking habits and oesophageal cancer in a high risk area in Northern Iran: Population based case-control study
Article
Full-text available
  • Feb 2009
  • Br Med J
To investigate the association between tea drinking habits in Golestan province, northern Iran, and risk of oesophageal squamous cell carcinoma. Population based case-control study. In addition, patterns of tea drinking and temperature at which tea was drunk were measured among healthy participants in a cohort study. Golestan province, northern Iran, an area with a high incidence of oesophageal squamous cell carcinoma. 300 histologically proved cases of oesophageal squamous cell carcinoma and 571 matched neighbourhood controls in the case-control study and 48 582 participants in the cohort study. Odds ratio of oesophageal squamous cell carcinoma associated with drinking hot tea. Nearly all (98%) of the cohort participants drank black tea regularly, with a mean volume consumed of over one litre a day. 39.0% of participants drank their tea at temperatures less than 60 degrees C, 38.9% at 60-64 degrees C, and 22.0% at 65 degrees C or higher. A moderate agreement was found between reported tea drinking temperature and actual temperature measurements (weighted kappa 0.49). The results of the case-control study showed that compared with drinking lukewarm or warm tea, drinking hot tea (odds ratio 2.07, 95% confidence interval 1.28 to 3.35) or very hot tea (8.16, 3.93 to 16.9) was associated with an increased risk of oesophageal cancer. Likewise, compared with drinking tea four or more minutes after being poured, drinking tea 2-3 minutes after pouring (2.49, 1.62 to 3.83) or less than two minutes after pouring (5.41, 2.63 to 11.1) was associated with a significantly increased risk. A strong agreement was found between responses to the questions on temperature at which tea was drunk and interval from tea being poured to being drunk (weighted kappa 0.68). Drinking hot tea, a habit common in Golestan province, was strongly associated with a higher risk of oesophageal cancer.
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Opium Consumption and the Risk of Traffic Injuries in Regular Users: A Case-Crossover Study in an Emergency Department
Article
The cause-specific annual death rate due to traffic injuries is around 30 in 100,000 in Iran. On the other hand, this country has the highest proportion of opiate users in the world. Little is known about the transient effect of opium on traffic injuries. The objective of this study was to explore the effect of opium consumption on traffic injuries in drivers who use opium. Seventy-five regular opium users who suffered traffic injuries were studied in a case-crossover investigation. The study subjects had been admitted to the single trauma emergency department in Kerman, a city in southeast Iran. The relative risk (RR) of short-term opium effect was estimated by considering frequency of driving after opium consumption during 6 hours before the accident in comparison to the usual frequency of driving after opium consumption by the same persons. Stratified data analysis was performed by the Mantel-Haenszel method. The opium consumption of drivers up to 6 hours before the accident was associated with an increased RR = 3.2, 95 percent confidence interval (CI): 1.9, 5.4. The third hour after consumption had the greatest magnitude of effect considering RR = 4.29, 95 percent CI:2.65, 6.95. These results suggest a heightened risk of traffic injuries after opium consumption in regular users. The RR in the third hour after consumption could be explained by considering the greater probability of driving compared to the immediate hours after use, rather than peak effect time of opiates. The results indicate necessity of regular assessment of all common drivers, especially truck and bus drivers, regarding use of opium.
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Tea Drinking Habits and Oesophagial Cancer in a High-Risk Area in Northern Iran: Population Based Case-Control Study
Article
  • Jun 2009
In a recently published paper in the "British Medical Journal", a joint collaboration of well-known international scientists represented by Islami et al. has tackled this issue.1 In a well-designed, laborious case-control study in Golestan, Iran, they looked at 300 cases of esophageal SCC and 571 age and sex matched neighborhood controls, assessed the temperature of the commonly used drink "tea" among them and compared it between the two groups. After adjusting for several confounders including ethnicity, daily vegetable intake, alcohol consumption, tobacco or opium use, duration of residence in rural areas, education level and car ownership (the latter two as indices of socio-economic status), they found that consuming hot tea is associated with significantly increased chance of developing esophageal SCC. The adjusted odds ratio(OR) for developing esophageal SCC in those who reported drinking "very hot tea" was 8.16 (95% CI: 3.93 to 16.91) as compared to those taking warm or lukewarm tea (P<0.001) and for those drinking "hot" tea the adjusted OR was 2.07 (95% CI: 1.28 to 3.35). According to Islami et al., 21.1% and 36.2% of the cases drank their tea "very hot" or "hot", respectively. Self-claim of "hot", "very hot", and "warm or "lukewarm" tea drinking correlated with the claimed time from pouring tea to its drinking by the individual (weighted kappa statistics: 0.69). They did not find any correlation between amount of tea consumed and development of esophageal SCC. They have also reported limited data of tea temperature measurement in addition to the self claims of tea drinking habits (as mentioned for the case-control study) from a large on-going cohort study in the same region. The authors conclude that it is probably the "hotness" rather than the "tea" which is responsible for this increased chance of SCC of esophagus. In an accompanying editorial, Whiteman suggests that people drink their tea at least 5 minutes after pouring it in their cups.
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Lifetime and baseline alcohol intake and risk of cancer of the upper aero‐digestive tract in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
Article
Recent alcohol consumption is an established risk factor for squamous cell carcinoma (SCC) of the upper aero-digestive tract. In contrast, the role of lifetime exposure to alcohol with regard to risk of SCC is not well established. Historical data on alcohol use are available in 271,253 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 2,330,381 person years, 392 incident SCC cases (279 men and 113 women) were identified. Cox regression was applied to model sex-specific associations between lifetime alcohol intake and SCC risk adjusting for potential confounders including smoking. Compared to men who drank 0.1-6.0 g/day alcohol at lifetime, the relative risks (RR) for developing SCC were significantly increased for men who drank 30.1-60.0 g/day (RR 1.65, 95% confidence interval:1.00-2.71), 60.1-96.0 g/day (RR 2.20, 95%CI 1.23-3.95), and >96.0 g/day, (RR 4.63, 95% CI 2.52-8.48), and for former drinkers (RR 4.14, 95%CI 2.38-7.19). These risk estimates did not considerably change when baseline alcohol intake was analyzed. Compared to women who drank 0.1-6.0 g/day alcohol intake at lifetime, the RR were significantly increased for women who drank >30 g/d (RR 6.05, 95%CI 2.98-12.3). Applying similar categories, the relative risk for baseline alcohol intake was 3.26 (95%CI 1.82-5.87). We observed a stronger association between alcohol intake at lifetime and risk of SCC in women compared to men (p for interaction = 0.045). The strong dose-response relation for lifetime alcohol use underscores that alcohol is an important risk factor of SCC of the upper aero-digestive tract throughout life.
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Environmental Causes of Esophageal Cancer
Article
  • Apr 2009
This article reviews the environmental risk factors and predisposing conditions for the two main histologic types of esophageal cancer. Tobacco smoking, excessive alcohol consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of esophageal squamous cell carcinoma. Results of investigations on other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and, probably, absence of H pylori in the stomach increase the risk of esophageal adenocarcinoma. Results of studies investigating other factors are also discussed.
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Vitamin E intake and Risk of Esophageal and Gastric Cancers in the NIH-AARP Diet and Health Study
Article
We investigated the association of dietary alpha-tocopherol, gamma-tocopherol and supplemental vitamin E intake with the risk of esophageal squamous cell carcinoma (n = 158), esophageal adenocarcinoma (n = 382), gastric cardia adenocarcinoma (n = 320) and gastric noncardia adenocarcinoma (GNCA; n = 327) in the NIH-AARP Diet and Health Study, a cohort of approximately 500,000 people. Data on dietary and supplemental vitamin E intake were collected using a validated questionnaire at baseline and were analyzed using Cox regression models. Intakes were analyzed as continuous variables and as quartiles. For dietary alpha-tocopherol, we found some evidence of association with decreased esophageal squamous cell carcinoma and increased esophageal adenocarcinoma risk in the continuous analyses, with adjusted hazard ratios and 95% confidence intervals of 0.90 (0.81-0.99) and 1.05 (1.00-1.11), respectively, per 1.17 mg (half the interquartile range) increased intake. However, in quartile analyses, the p value for trend was nonsignificant for both these cancers. There was no association between dietary alpha-tocopherol and gastric cardia adenocarcinoma or GNCA. We observed no statistically significant associations with gamma-tocopherol. For supplemental vitamin E, the results were mainly null, except for a significantly lower risk of GNCA with higher doses of supplemental vitamin E. An increase of 71 mg/day (half the interquartile range) in supplemental vitamin E had an hazard ratio (95% confidence interval) of 0.92 (0.85-1.00) and the p value for trend in the quartile analysis was 0.015.
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Selection of Controls in Case-Control Studies: II. Types of Controls
Article
  • Jun 1992
  • AM J EPIDEMIOL
Types of control groups are evaluated using the principles described in paper 1 of the series, “Selection of Controls in Case-Control Studies* (S. Wacholder et al. Am J Epidemiol 1992; 135: 1019–28). Advantages and disadvantages of population controls, neighborhood controls, hospital or registry controls, medical practice controls, friend controls, and relative controls are considered. Problems with the use of deceased controls and proxy respondents are discussed. Am J Epidemiol 1992; 135: 1029–41
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