Cigarette Smoking and Adenocarcinomas of the Esophagus and Esophagogastric Junction: A Pooled Analysis From the International BEACON Consortium

Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, 6120 Executive Blvd., Bethesda, MD 20852-7234, USA.
Journal of the National Cancer Institute (Impact Factor: 12.58). 09/2010; 102(17):1344-53. DOI: 10.1093/jnci/djq289
Source: PubMed


Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose-response, and duration of cigarette smoking cessation.
We used primary data from 10 population-based case-control studies and two cohort studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided.
The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose-response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and > or =10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar.
Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.

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    • "However, in addition to those variables included in the minimally adjusted models, we included the following covariates in all study-specific maximally adjusted models given previous evidence of associations between these exposures and adenocarcinomas of the esophagus: BMI (categorical: <25, 25–29.9, ≥30) [18], education (study-specific) [19], [20], alcohol consumption (categorical: <7, 7–20, ≥21 drinks per week) [21], and cigarette smoking (categorical: 0, 1–14, 15–29, 30–44, ≥45 pack-years) [13]. Results were not materially different between minimally and maximally adjusted models, thus we present only the latter results. "
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    ABSTRACT: Background Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues. Methods Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted. Results Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index. Conclusions This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.
    Full-text · Article · Jul 2014 · PLoS ONE
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    • "In cohort studies, cigarette smoking doubles the risk of EAC [17, 18], whereas in the sparse work in BE, it is former, rather than current smoking, for which positive associations are reported [12, 19]. A pooled analysis of two cohort and ten case–control studies reported strong associations between cigarette smoking with both esophageal adenocarcinoma and junctional adenocarcinoma [20]. For alcohol, there are a limited number of prospective studies which report no associations for either BE or EAC [12, 17, 18] and no associations according to the specific intakes of either beer, wine or spirits. "
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    ABSTRACT: The timing of the risk factors cigarette smoking, alcohol and obesity in the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) is unclear. To investigate these exposures in the aetiology of BE and EAC in the same population. The cohort included 24,068 men and women, aged 39-79 years, recruited between 1993 and 1997 into the prospective EPIC-Norfolk Study who provided information on anthropometry, smoking and alcohol intake. The cohort was monitored until December 2008 and incident cases identified. One hundred and four participants were diagnosed with BE and 66 with EAC. A body mass index (BMI) above 23 kg/m(2) was associated with a greater risk of BE [BMI ≥23 vs. 18.5 to <23, hazard ratio (HR) 3.73, 95 % CI 1.37-10.16], and within a normal BMI, the risk was greater in the higher category (HR 3.76, 95 % CI 1.30-10.85, BMI 23-25 vs. 18.5 to >23 kg/m(2)). Neither smoking nor alcohol intake were associated with risk for BE. For EAC, all BMI categories were associated with risk, although statistically significant for only the highest (BMI >35 vs. BMI 18.5 to <23, HR 4.95, 95 % CI 1.11-22.17). The risk was greater in the higher category of a normal BMI (HR 2.73, 95 % CI 0.93-8.00, p = 0.07, BMI 23-25 vs. 18.5 to >23 kg/m(2)). There was an inverse association with ≥7 units alcohol/week (HR 0.51, 95 % CI 0.29-0.88) and with wine (HR 0.49, 95 % CI 0.23-1.04, p = 0.06, drinkers vs. non-drinkers). Obesity may be involved early in carcinogenesis and the association with EAC and wine should be explored. The data have implications for aetiological investigations and prevention strategies.
    Full-text · Article · Feb 2014 · Digestive Diseases and Sciences
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    • "The Netherlands Cohort Study found a relative risk of 0.9 (95% CI, 0.6–1.3) among those in the highest quintile of dietary folate intake, compared with those in the lowest (Cook et al, 2010). Similarly, a more recent study examined stomach cancer risk in relation to dietary folate intake in the Swedish Mammography Cohort and reported no association between the two (RR (95% CI), 1.04 (0.61, 1.86)) (Bailey, 1990). "
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    ABSTRACT: Background: Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer. Methods: We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492 293 men and women. Results: We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1.91 (1.17, 3.10)), but no association with high intake. Folate intake was not associated with esophageal adenocarcinoma, gastric cardia adenocarcinoma, or non-cardia gastric adenocarcinoma. The intakes of methionine, vitamin B6, and vitamin B12 were not associated with esophageal and gastric cancer. Conclusion: Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma.
    Full-text · Article · Jan 2014 · British Journal of Cancer
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