Jessie Steevens

Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: A prospective cohort study

Objective: Alcohol consumption and cigarette smoking may be differentially associated with oesophageal squamous cell carcinoma (OSCC), oesophageal adenocarcinoma (OAC), gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). However, because this was based on retrospective studies, these hypotheses were examined in a prospective cohort. Methods: The prospective Netherlands Cohort Study consists of 120 852 participants who completed a baseline questionnaire on diet and other cancer risk factors in 1986. After 16.3 years of follow-up, 107 OSCC, 145 OAC, 164 GCA and 491 GNCA cases were available for analysis using Cox proportional hazards models and the case–cohort approach. Results: The multivariable adjusted incidence rate ratio (RR) for OSCC was 4.61 (95% CI 2.24 to 9.50) for ⩾30 g ethanol/day compared with abstainers (p trend <0.001), while no associations with alcohol were found for OAC, GCA or GNCA. Compared with never smokers, current smokers had RRs varying from 1.60 for GCA to 2.63 for OSCC, and were statistically significant or borderline statistically significant. Frequency, duration and pack-years of smoking were independently associated with risk of all four cancers. A positive interaction was found between alcohol consumption and smoking status regarding OSCC risk. The RR for current smokers who consumed >15 g/day of ethanol was 8.05 (95% CI 3.89 to 16.60; p interaction = 0.65), when compared with never smokers who consumed <5 g/day of ethanol. Conclusions: This prospective study found alcohol consumption to be associated with increased risk of only OSCC. Cigarette smoking was associated with risk of all four cancers.

Trends in incidence of oesophageal and stomach cancer subtypes in Europe.

Objective Time trend studies in the USA have shown that the incidences of adenocarcinomas of the oesophagus and gastric cardia have risen strongly since the 1970s, whereas the incidence of squamous cell carcinomas of the oesophagus has declined. Earlier, we found that the incidence of these adenocarcinomas also rose in some European countries until the early 1990s. The main goal of this study was to investigate more recent trends in the incidence of oesophageal and stomach cancer subtypes in the European countries. Methods Eurocim cancer incidence data of 23 cancer registries from 13 European countries were used to investigate the incidence trends in oesophageal and stomach cancer subtypes during the 1983–1997 period. We calculated estimated annual percentage changes (EAPCs) in European age-standardized incidence rates and 95% confidence intervals. Results The incidence of adenocarcinomas of the oesophagus and gastric cardia rose in most, but not all, registration areas (EAPCs were usually 1–7%), the strongest in the UK and Ireland. Oesophageal squamous cell carcinoma incidence rose mostly in Northern European and Slovakian men (EAPCs: 1–5%) and in women from all regions (EAPCs: 1–8%), but declined mostly in Southern and Western European men (EAPCs: −1 to −5%). Conclusion Our results are partly in line with earlier findings on adenocarcinomas of the oesophagus and gastric cardia. There was, however, substantial heterogeneity in trends of subtypes of these cancers within Europe. There may be different risk factors for these cancers, and the prevalence of these risk factors may differ among countries.

Vegetables and fruits consumption and risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.

Prospective epidemiologic data on vegetables and fruits consumption and risk of subtypes of esophageal and gastric cancer are sparse. We studied the association between vegetables and fruits consumption and risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in the Netherlands Cohort Study. In 1986, 120,852 Dutch men and women aged 55–69 filled out a questionnaire on diet and other cancer risk factors. After 16.3 years of follow‐up, 101 ESCC, 144 EAC, 156 GCA, 460 GNCA cases and 4,035 subcohort members were available for case–cohort analysis using Cox proportional hazards models. Multivariable adjusted incidence rate ratios (RRs) were generally below unity. Total vegetable consumption was nonsignificantly inversely associated with EAC and ESCC risk, but not with GCA and GNCA risk. Significant inverse associations were observed for raw vegetables and EAC risk [RR per 25 g/day: 0.81, 95% confidence interval (CI) 0.68–0.98], and Brassica vegetables and GCA risk (RR per 25 g/day: 0.72, 95% CI 0.54–0.95). Total fruit consumption was associated with a nonsignificantly decreased EAC risk. Citrus fruits were inversely associated with EAC and GCA risk (RRs for highest vs. lowest intake: 0.55, 95% CI 0.31–0.98 and 0.38, 95% CI 0.21–0.69, respectively). Specifically for current smokers, vegetables and possibly also fruits intake was inversely associated with ESCC and EAC risk. Consumption of (specific groups of) vegetables and fruits may protect against subtypes of esophageal and gastric cancer.

Selenium status and the risk of esophageal and gastric cancer subtypes: the Netherlands Cohort Study.

BACKGROUND & AIMS Selenium may protect against the development of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cardia adenocarcinoma (GCA). Only in very few studies have the associations with ESCC and GCA been investigated, and no epidemiologic studies exist on EAC. METHODS We studied the association between selenium and risk of ESCC, EAC, and GCA within the prospective Netherlands Cohort Study, conducted among 120,852 men and women aged 55-69 years at baseline. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 16.3 years of follow-up, 64 ESCC, 112 EAC, and 114 GCA cases and 2072 subcohort members were available for case-cohort analysis. Incidence rate ratios (RR) were calculated using Cox proportional hazards models. RESULTS In multivariable analyses of selenium status, we found an inverse association with ESCC (RR(per standard unit increment), 0.80; 95% confidence interval [CI]: 0.67-0.96) and a borderline significant inverse association with GCA (RR, 0.91; 95% CI: 0.80-1.02). No overall association was observed for EAC (RR, 1.05; 95% CI: 0.95-1.15), but, for women and never smokers, significant inverse associations were found (RR(per standard unit increment), 0.72; 95% CI: 0.61-0.84 and RR(per standard unit increment), 0.74; 95% CI: 0.64-0.86, respectively). CONCLUSIONS This prospective study supports an inverse association between toenail selenium and risk of ESCC and GCA and suggests an inverse association with risk of EAC in subgroups (women, never smokers, and low antioxidant consumers). These associations need confirmation.

Tea and coffee drinking and ovarian cancer risk: results from the Netherlands Cohort Study and a meta-analysis

In a cohort study, ovarian cancer (280 cases) showed no significant association with tea or coffee, the multivariable rate ratios being 0.94 (95% confidence interval (CI): 0.89, 1.00) and 1.04 (95% CI: 0.97, 1.12) per cup per day, respectively. A meta-analysis also produced no significant findings overall, though the cohort studies showed a significant inverse association for tea.

A Prospective Cohort Study on Overweight, Smoking, Alcohol Consumption, and Risk of Barrett's Esophagus

Background: Barretts esophagus (BE) is a precursor lesion of esophageal adenocarcinoma. Besides gastroesophageal reflux, possible risk factors for BE include overweight, cigarette smoking, and alcohol consumption. Our objective was to study these associations by using prospective data. Methods: The prospective Netherlands Cohort Study, initiated in 1986, consists of 120,852 men and women, aged 55 to 69 years at baseline. At baseline, all subjects completed a questionnaire on dietary habits and lifestyle. After 16.3 years of follow-up, 370 BE cases with specialized intestinal metaplasia and 3,866 subcohort members were available for case–cohort analysis. Cox proportional hazards models were used to calculate incidence rate ratios (RR) and 95% CIs. Results: Body mass index (BMI) at baseline was associated with risk of BE in women [multivariable adjusted RR per 1 kg/m2, 1.07 (1.03–1.11)] but not in men [RR per 1 kg/m2, 0.99 (0.93–1.05)]. The association in women was not specifically due to abdominal overweight. Former cigarette smokers were at increased risk of BE (RR = 1.33, 95% CI: 1.00–1.77), but current smokers were not. Smoking duration showed a positive association with BE risk (Ptrend = 0.03). For alcohol consumption, the RR per 10 g ethanol/d was 0.95 (0.87–1.03). Conclusions: Increased BMI was a risk factor for BE in women but not in men. Several aspects of cigarette smoking were positively associated with BE risk. Alcohol consumption was not associated with an increased risk of BE. Impact: Future research should focus on risk factors both for development and for progression of BE to esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 20(2); 345–58. ©2010 AACR.

Total Cancer Incidence and Overall Mortality Are Not Increased Among Patients With Barrett's Esophagus

BACKGROUND & AIMS Barretts esophagus (BE) increases risk for esophageal adenocarcinoma, but it is not clear how it affects risk for other cancers or overall mortality. We analyzed data from a population-based cohort of subjects with BE. METHODS The Netherlands Cohort Study was initiated in 1986 and included 120,852 participants (55-69 years old at baseline). Until December 2002, 626 incident cases of BE (excluding nonintestinal metaplasia) were identified by record linkage with the nationwide Pathology Registry. This cohort was followed for a median period of 5.7 years; data on cancer and mortality were obtained from record linkage to the Netherlands Cancer Registry and Statistics Netherlands. The expected number of cases was calculated using national cancer incidence and mortality data. RESULTS In the BE cohort, 13 individuals developed esophageal cancer and 5 developed gastric cancer. The ratio of observed:expected (O:E) incidence of esophageal and gastric cancer was 10.0 (95% confidence interval [CI], 5.3-17.1) and 1.8 (95% CI, 0.6-4.2), respectively. Total cancer incidence (excluding esophageal and gastric cancer) increased in the BE cohort, although not by a statistically significant amount (O:E, 1.3; 95% CI, 1.0-1.6). Of cancer subtypes, incidences of small intestinal and pancreatic cancer increased in subjects with BE, but not by a statistically significant amount, after exclusion of data from the first 6 months of follow-up. During the follow-up period, 225 individuals with BE died. Mortality from all causes (excluding esophageal and gastric cancer) was not increased among subjects with BE (O:E, 1.0; 95% CI, 0.9-1.2), nor was mortality from specific causes of death. CONCLUSIONS The incidence of esophageal cancer was increased in a population-based cohort of subjects with BE. However, when esophageal and gastric cancers were excluded, total cancer incidence and overall mortality were not increased among subjects with BE.

Treatment with curative intent of stage III non-small cell lung cancer patients of 75 years: A prospective population-based study

BACKGROUND There is little data on the survival of elderly patients with stage III non-small cell lung cancer (NSCLC). METHODS Patients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included. FINDINGS One thousand and two patients with stage III were diagnosed, of which 237 were 75 years or older. From 228 patients, co-morbidity scores were available. Only 33/237 patients (14.5%) had no co-morbidities, 195 (85.5%) had one or more important co-morbidities, 60 (26.3%) two or more co-morbidities, 18 (7.9%) three or more co-morbidities and 2 patients (0.9%) suffered from four co-morbidities. Forty-eight percent were treated with curative intent. No significant difference in Charlson co-morbidity, age or gender was found between patients receiving curative or palliative intent treatment. Treatment with curative intent was associated with increased overall survival (OS) compared to palliative treatment: median OS 14.2 months (9.6-18.7) versus 5.2 months (4.3-6.0), 2-year OS 35.5% versus 12.1%, for curative versus palliative treatment. FINDINGS Patients who received only radiotherapy with curative intent had a median OS of 11.1 months (95% confidence interval [95% CI] 6.4-15.8) and a 5-year OS of 20.3%; for sequential chemotherapy and radiotherapy, the median OS was 18.0 months (95% CI 12.2-23.7), with a 5-year OS of 14.9%. Only four patients received concurrent chemo-radiation. INTERPRETATION In this prospective series treating elderly patients with stage III NSCLC with curative intent was associated with significant 5-year survival rates.

Abstract A113: Toenail selenium and the risk of esophageal and gastric cancer subtypes: The Netherlands Cohort Study

Purpose: Selenium may protect against the development of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA). Only in very few studies have the associations with ESCC and GCA been investigated, and no epidemiologic studies exist on EAC. Methods: We studied the association between selenium and risk of ESCC, EAC, and GCA within the prospective Netherlands Cohort Study, conducted among 120,852 men and women aged 55–69 years at baseline. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 16.3 years of follow‐up, 64 ESCC, 112 EAC, and 114 GCA cases and 2072 subcohort members with toenail selenium data were available for case‐cohort analysis. Incidence rate ratios (RR) were calculated using Cox proportional hazards models. Results: In multivariable analyses of selenium status, we found an inverse association with ESCC (RR quartile 4 versus quartile 1 0.37, 95% confidence intervals (CI) 0.16–0.86), and a borderline significant inverse association with GCA (RR 0.52, 95% CI 0.27–1.02). No overall association was observed for EAC (RR 0.76, 95% CI 0.41–1.40), although results suggested an inverse association in women. Stratified analyses showed stronger associations in never smokers, and (only for EAC) in subjects with a low antioxidant intake. Conclusions: This prospective study supports an inverse association between toenail selenium and risk of ESCC and GCA and suggests an inverse association with risk of EAC in subgroups (women, never smokers, and low antioxidant consumers). These associations need confirmation. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A113.

Abstract A99: A prospective cohort study on the associations between alcohol consumption and smoking and risk of subtypes of esophageal and stomach cancer

A99 Background Previous studies have suggested that the etiology of histological subtypes of esophageal cancer and of topographical subtypes of stomach cancer may differ. It was found that risk of esophageal squamous cell carcinoma (ESCC) was strongly associated with alcohol consumption and tobacco smoking. However, esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) had no association with alcohol and a much weaker association with smoking. Because most studies were cases control studies, and only few cohort studies have been performed, the aim of our study is to investigate these associations within a large-scale prospective cohort study. Methods The Netherlands Cohort Study was initiated in 1986, when participants (58,279 men and 62,573 women) completed a self-administered questionnaire on risk factors for cancer, including alcohol consumption and smoking habits. Follow-up for incident cancer cases was established by record linkages to the pathology registry and cancer registries. After 16.3 years, we identified 120 ESCC cases, 168 EAC cases and 187 GCA cases. For reasons of efficiency, we used a case-cohort approach, for which a subcohort (n = 4,438) was randomly sampled from the cohort at baseline. Multivariable Cox proportional hazards models estimated incidence rate ratios (RR) and corresponding 95% confidence intervals (95% CI). We corrected for age, sex, alcohol consumption and smoking status, frequency and duration. The following confounders were added if they changed the RR by >5%: fruit consumption, vegetable consumption, energy intake, non-occupational physical activity, BMI, and socioeconomic status. Results The multivariable RRs associated with alcohol consumption were 1.30 per 10 g ethanol/day increment (95% CI 1.20-1.42, p The RRs (95% CI) of ESCC for former smokers and current smokers were 1.39 (0.75-2.59) and 2.65 (1.49-4.70), respectively (p-trend Conclusions The results of this cohort study suggest that alcohol and cigarette smoking are differently associated with ESCC than with EAC and GCA. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A99.