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.     

Tree nut,peanut, and peanut butter consumption and the risk of gastric and esophageal cancer subtypes: the Netherlands Cohort Study

Background

Nut consumption has been associated with reduced cancer-related mortality. However, it is unclear whether nut consumption also reduces the risk of esophageal and gastric cancer subtypes. We prospectively investigated the relationship of tree nut, peanut, and peanut butter intake with risk of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA) in the Netherlands Cohort Study.

Methods

In 1986, 120,852 males and females, aged 55–69 years, completed a baseline questionnaire on diet and cancer risk factors. After 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA cases, and 3,720 subcohort members were available for multivariable Cox regression analyses, using a case–cohort approach.

Results

Increased total nut consumption was significantly associated with a decreased risk of ESCC and GNCA [HRs (95% CIs) for 10?+?g/day vs. nonconsumers?=?0.54 (0.30–0.96) and 0.73 (0.55–0.97), respectively], but not with EAC and GCA risk. Similar trends were observed for tree nut and peanut intake, which were mostly nonsignificant. For peanut butter intake, no significant associations were found. When excluding the first four years of follow-up to reduce the possible influence of reversed causation, the relation between nut consumption and ESCC risk attenuated, but remained inverse.

Conclusions

Our findings suggest that increased tree nut and peanut consumption is inversely associated with GNCA risk and possibly with ESCC risk, but not with the risk of the other esophageal and gastric cancer subtypes.

     

Serum ghrelin and esophageal and gastric cancer in two cohorts in China

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case–cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case–control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR _Q1:Q4) for GNCA in NIT was 1.35 (95% CI: 0.89–2.05; p-trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02–2.70; p-trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR _Q1:Q4 = 2.00, 95% CI: 1.45–2.77; p-trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR _Q1:Q4 = 0.65, 95% CI: 0.45–0.92; p-trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.     

Vitamin E intake and risk of esophageal and gastric cancers in the NIH‐AARP Diet and Health Study

We investigated the association of dietary α‐tocopherol, γ‐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 α‐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 α‐tocopherol and gastric cardia adenocarcinoma or GNCA. We observed no statistically significant associations with γ‐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. © 2009 UICC     

Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH-AARP diet and health study

The aim of our study was to investigate whether intakes of total fat and fat subtypes were associated with esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cardia or gastric noncardia adenocarcinoma. From 1995-1996, dietary intake data was reported by 494,978 participants of the NIH-AARP cohort. The 630 EAC, 215 ESCC, 454 gastric cardia and 501 gastric noncardia adenocarcinomas accrued to the cohort. Cox proportional hazards regression was used to examine the association between the dietary fat intakes, whilst adjusting for potential confounders. Although apparent associations were observed in energy-adjusted models, multivariate adjustment attenuated results to null [e.g., EAC energy adjusted hazard ratio (HR) and 95% confidence interval (95% CI) 1.66 (1.27-2.18) p for trend <0.01; EAC multivariate adjusted HR (95% CI) 1.17 (0.84-1.64) p for trend = 0.58]. Similar patterns were also observed for fat subtypes [e.g., EAC saturated fat, energy adjusted HR (95% CI) 1.79 (1.37-2.33) p for trend <0.01; EAC saturated fat, multivariate adjusted HR (95% CI) 1.27 (0.91-1.78) p for trend = 0.28]. However, in multivariate models an inverse association for polyunsaturated fat (continuous) was seen for EAC in subjects with a body mass index (BMI) in the normal range (18.5-<25 kg/m(2)) [HR (95% CI) 0.76 (0.63-0.92)], that was not present in overweight subjects [HR (95% CI) 1.04 (0.96-1.14)], or in unstratified analysis [HR (95% CI) 0.97 (0.90-1.05)]. p for interaction = 0.02. Overall, we found null associations between the dietary fat intakes with esophageal or gastric cancer risk; although a protective effect of polyunsaturated fat intake was seen for EAC in subjects with a normal BMI.     

A possible link between famine exposure in early life and future risk of gastrointestinal cancers: Implications from age‐period‐cohort analysis

The Chinese famine in 1958–1962 was one of the worst in human history, but its potential influence on cancer risks is uncertain. Using cancer incidence data in Shanghai, China, during 1983–2007, we calculated age‐specific incidence rates of gastrointestinal cancers in birth cohorts exposed to the Chinese famine in different periods of life and a non‐exposed reference cohort. Age‐period‐cohort regressions estimated the overall relative risks of gastrointestinal cancers in each birth cohort. A total of 212,098 new cases of gastrointestinal cancer were identified during the study period (129,233 males and 82,865 females), among whom 18,146 had esophageal cancer, 71,011 gastric cancer, 55,864 colorectal cancer, 42,751 liver cancer, 9,382 gallbladder cancer and 14,944 had pancreatic cancer. The risk of esophageal, gastric, colorectal and liver cancers was higher in cohorts exposed to the Chinese famine in early life than in the reference cohort, except for esophageal cancer in women. The risk of esophageal, liver and colorectal cancers was particularly high in men exposed to famine during early childhood (0–9 years). There were no clear associations between famine exposure and the risk of pancreatic or gallbladder cancer. This study suggests an increased risk of esophageal, gastric, liver and colorectal cancers associated with childhood exposure to the Chinese famine. These findings indicate a need for further investigations confirming the results and identifying the underlying mechanisms.     

Association between cigarette smoking and colorectal cancer in the Women's Health Initiative

The evidence linking cigarette smoking to the risk of colorectal cancer is inconsistent. We investigated the associations between active and passive smoking and colorectal cancer among 146,877 Women's Health Initiative participants. Women reported detailed smoking histories at enrollment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between smoking and overall and site-specific risk of colorectal cancer. Invasive colorectal cancer was diagnosed in 1242 women over an average of 7.8 years (range = 0.003-11.2 years) of follow-up. In adjusted analyses, statistically significant positive associations were observed between most measures of cigarette smoking and risk of invasive colorectal cancer. Site-specific analyses indicated that current smokers had a statistically significantly increased risk of rectal cancer (HR = 1.95, 95% CI = 1.10 to 3.47) but not colon cancer (HR = 1.03, 95% CI = 0.77 to 1.38), compared with never smokers. Passive smoke exposure was not associated with colorectal cancer in adjusted analyses. Thus, active exposure to cigarette smoking appears to be a risk factor for rectal cancer.     

Consumption of salted meat and its interactions with alcohol drinking and tobacco smoking on esophageal squamous‐cell carcinoma

Etiology of esophageal cancer has not yet been clearly documented, especially in high‐risk regions. To evaluate the association between salted meat intake and esophageal squamous‐cell carcinoma (ESCC) and to explore its joint effects with alcohol drinking and smoking, a population‐based case–control study was conducted in a high ESCC risk area in China, including 942 incident ESCC cases and 942 age‐ and sex‐matching controls. A validated food frequency questionnaire was used to collect information on dietary factors, alcohol drinking and tobacco smoking. Conditional logistic regressions were applied to estimate the association between salted meat intake and ESCC and its interactions with alcohol drinking and smoking, with adjustment for other confounders, including total energy intake. Salted meat intake was associated with an increased risk of ESCC, showing an exposure–response relationship (p for trend <0.001). Consumption of 50 g salted meat per week was related to an increased risk by 18% (odds ratio = 1.18, 95% confidence interval: 1.13–1.23). Salted meat in combination with either alcohol drinking or smoking had a greater risk than salted meat alone, which was more than additive. The strongest association was seen in the combination of all the three factors, particularly at the highest level of salted meat intake (odds ratio = 29.27, 95% confidence interval: 13.21–64.89). Salted meat intake is strongly associated with ESCC and its interactions with alcohol drinking and/or smoking highlights the significance of reducing salted meat intake among smokers and drinkers with respect to ESCC prevention.     

Prospective study of Helicobacter pylori antigens and gastric noncardia cancer risk in the nutrition intervention trial cohort

Helicobacter pylori (H. pylori) infection is the strongest known risk factor for gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of noncardia gastric cancer in Linxian, China. We included 448 GNCA cases and 1242 controls from two time points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to ≥4 of the 15 included antigens. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk factors. In addition, we undertook a meta‐analysis combining H. pylori multiplex serology data from both time points. H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both time points in a meta‐analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA. We identified six individual antigens that confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen that may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA.     

Body mass index and risk of gastric cancer: A 30‐year follow‐up study in the Linxian general population trial cohort

Although a number of previous studies have noted either positive or no association for body mass index (BMI) and gastric cancer risk, little evidence exists in the Chinese population. We prospectively examined the associations of BMI with risk of gastric cancer in the Linxian General Population Trial cohort, with 29 584 healthy adults enrolled in 1985 and followed through to the end of 2014. Body weight and height were measured during physical examination at baseline and BMI was calculated as weight in kilograms divided by height in meters squared. Body mass index from 138 subjects was missing, and a total of 29 446 participants were included in the final analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. During 30 years of follow‐up, we confirmed 1716 newly diagnosed gastric cardia adenocarcinoma (GCA) cases and 626 new gastric non‐cardia adenocarcinoma (GNCA) cases. Overall, compared to the lowest quartile (BMI <20.32 kg/m²), subjects in the fourth quartile (BMI ≥23.31 kg/m²) subjects had lower risk of developing GNCA (hazard ratio, 0.65; 95% confidence interval, 0.51–0.83). Age‐ and sex‐specific analyses showed that this protective effect was only observed in men and older (52 + years) persons. No associations were observed for BMI with GCA incidence. Higher BMI was associated with decreased risk of GNCA in this population, particularly in men and older persons. Future studies are needed to confirm these findings. The trial is registered with ClinicalTrials.gov: NCT00342654.     

Dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study

Nitrate and nitrite are precursors of endogenously formed N‐nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40–70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77‐item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow‐up, we identified 619 colorectal cancer cases (n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73–1.59). However, among women with vitamin C intake below the median (83.9 mg day^?1) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15–5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer.     

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980–2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28–1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92–1.39) and 1.55 (95% CI 1.04–2.31) 10–14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83–1.52; HR 1.08, 95% CI 0.79–1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.     

Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF‐/KRAS‐ but not BRAF+ colorectal cancer

Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10‐year periods from age 20 using recalled frequency and quantity of beverage‐specific consumption for 38,149 participants aged 40–69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose‐dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow‐up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04–1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (p _homogeneity = 0.02). Alcohol intake was associated with increased risks of KRAS + (HR = 1.07, 95% CI: 1.00–1.15) and BRAF ?/KRAS ? (HR = 1.05, 95% CI: 1.00–1.11) but not BRAF + tumors (HR = 0.89, 95% CI: 0.78–1.01; p _homogeneity = 0.01). Alcohol intake is associated with an increased risk of KRAS + and BRAF ?/KRAS‐ tumors originating via specific molecular pathways including the traditional adenoma‐carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma‐carcinoma pathway.     

Menopausal hormone therapy and the risk of esophageal and gastric cancer

A protective effect of female sex hormones has been suggested to explain the male predominance in esophageal and gastric adenocarcinoma, but evidence is lacking. We aimed to test whether menopausal hormone therapy (MHT) decreases the risk of these tumors. For comparison, esophageal squamous cell carcinoma was also assessed. This population‐based matched cohort study included all women who had ever used systemic MHT in Sweden in 2005–2012. A comparison cohort of non‐users of MHT was matched to the MHT‐users regarding age, parity, thrombotic events, hysterectomy, diabetes, obesity, smoking‐related diseases and alcohol‐related diseases. Individuals with any previous cancer were excluded. Data on MHT use, cancer, comorbidity and mortality were collected from well‐established Swedish nationwide registers. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression. Different MHT regimens and age groups were compared in sub‐group analyses. We identified 290,186 ever‐users and 870,165 non‐users of MHT. Ever‐users had decreased ORs of esophageal adenocarcinoma (OR = 0.62, 95% CI 0.45–0.85, n = 46), gastric adenocarcinoma (OR = 0.61, 95% CI 0.50–0.74, n = 123) and esophageal squamous cell carcinoma (OR = 0.57, 95% CI 0.39–0.83, n = 33). The ORs were decreased for both estrogen‐only MHT and estrogen and progestin combined MHT, and in all age groups. The lowest OR was found for esophageal adenocarcinoma in MHT‐users younger than 60 years (OR = 0.20, 95% CI 0.06–0.65). Our study suggests that MHT‐users are at a decreased risk of esophageal and gastric adenocarcinoma and also of esophageal squamous cell carcinoma. The mechanisms behind these associations remain to be elucidated.     

Smoking,snus use and risk of right‐ and left‐sided colon,rectal and anal cancer: A 37‐year follow‐up study

Although some authorities consider smoking to be an established risk factor for colorectal cancer, the international literature is not entirely consistent. Further, only 1 study has addressed the association with smokeless tobacco and none with Scandinavian moist snuff (snus). This retrospective cohort study included 336,381 male Swedish construction workers with detailed information on tobacco use at cohort entry in 1971–1992. Complete follow‐up through 2007 was accomplished by means of linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards regression models estimated relative risks, adjusted for age and body mass index. Subjects who were never‐users of any tobacco served as reference. After up to 37 years of follow‐up, pure smoking was associated with a marginally increased risk of colon cancer (HR 1.08, 95% CI 0.99–1.19), a modestly elevated risk of rectal cancer (HR 1.16, 95% CI 1.04–1.30) and a substantial excess risk of anal cancer (HR 2.41, 95% CI 1.06–5.48). Snus use was not significantly associated with an increased risk of colorectal or anal cancer, although the point estimate for colon cancer was similar to that observed among smokers. Swedish data provide meager support for the association between tobacco use and colorectal cancer. A general tendency among Swedish men to quit smoking in recent decades might have attenuated true associations. A link between smoking and anal cancer was confirmed.     

Endoscopy for gastroesophageal reflux disease and survival in esophageal adenocarcinoma

Gastroesophageal reflux disease (GERD) is a risk factor of esophageal adenocarcinoma (EAC) and the most common indication for upper gastrointestinal endoscopy. Yet, whether GERD or endoscopy practice influence survival in EAC is largely unknown and was assessed in our study.This nationwide cohort study included all Swedish residents diagnosed with EAC in 1997–2013 with follow-up to 2018. Exposures were history of GERD and endoscopies prior to EAC. The main outcome was EAC-specific 5-year mortality. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounders. Among 6,600 EAC patients (79.3% males, median age 70 years) followed for 9,138 person-years, 440 (6.7%) had GERD and 592 (9.0%) had ≥1 endoscopy before EAC diagnosis. GERD was associated with a decreased risk of mortality (adjusted HR 0.71, 95% CI 0.64–0.80), which was only slightly attenuated by adjustment for prior endoscopies (HR 0.79, 95% CI 0.70–0.90), and further adjustments also for tumor stage and surgical resection (HR 0.74, 95% CI 0.62–0.89). Compared to EAC patients without prior endoscopy, mortality was unchanged in GERD patients having undergone 1 or 2 endoscopies before EAC diagnosis (HR 1.02, 95% CI 0.80–1.31, for 1 endoscopy; HR 0.90, 95% CI 0.63–1.30, for 2 endoscopies), while the mortality was decreased in patients with ≥3 endoscopies (HR 0.55, 95% CI 0.36–0.85). Our study indicates that GERD may be associated with a better prognosis in the event of EAC; however, the use of endoscopy screening has a limited impact on survival unless performed very frequently.     

Cigarette smoking and colorectal cancer incidence and mortality: Systematic review and meta‐analysis

The association between cigarette smoking and colorectal cancer (CRC) has been controversial. To synthesize the available data, we conducted a comprehensive meta‐analysis of all prospective studies. A total of 36 studies were included in our meta‐analysis. We examined the association between smoking and CRC, colon cancer and rectal cancer in terms of incidence and mortality. Separate analyses were conducted for smoking status, daily cigarette consumption, duration, pack‐years and age of initiation. Relative to nonsmokers, current and former smokers had a significantly increased risk of CRC incidence and mortality, respectively. When CRC data were combined with colon/rectal cancer data, current smokers had a significantly increased risk of CRC incidence. All 4 dose–response variables examined—daily cigarette consumption (RR = 1.38 for an increase of 40 cigarettes/day), duration (RR = 1.20 for an increase of 40 years of duration), pack‐years (RR = 1.51 for an increase of 60 pack‐years) and age of initiation (RR = 0.96 for a delay of 10 years in smoking initiation)—were significantly associated with CRC incidence (all p‐values < 0.0001). The relationship between duration of smoking and rectal cancer incidence was also significant. Among the subset of studies that distinguished cancer by site, a higher risk was seen for rectal cancer than for colon cancer for all analyses. Among prospective studies, a consistent association exists between smoking and CRC. The association is stronger for rectal cancer than for colon cancer in the subset of studies that differentiated cancer by site. © 2008 Wiley‐Liss, Inc.     

Helicobacter pylori infection,chronic atrophic gastritis and risk of stomach and esophagus cancer: Results from the prospective population-based ESTHER cohort study

Helicobacter pylori (H. pylori) infection is considered as principal cause of gastric cancer. It is further associated with a reduced risk of esophageal adenocarcinomas. In a large prospective population-based cohort study including 9,949 subjects with average observation time of 13.8 years, we assessed the risk of invasive gastric and esophageal cancer according to H. pylori infection and presence of chronic atrophic gastritis (CAG). Incidence rates and hazard ratios (HR) derived by Cox proportional hazards models and adjusted for relevant confounders were derived by seroprevalence of H. pylori and cytotoxin-associated gene A (CagA) antibodies and presence of CAG based on serological markers at baseline, respectively. During follow-up, 30 cases of noncardia gastric cancer and 33 cases of esophageal cancer were observed. Infection by H. pylori without and with expression of CagA was associated with a 5.2-fold (95% confidence interval 1.00–27.1) and an 18.2-fold (4.3–77.4) increase of noncardia gastric cancer incidence. A 0.65-fold decreased risk of esophageal adenocarcinomas (HR 0.35, 0.12–0.97) was observed among H. pylori-infected individuals. In participants infected with CagA expressed H. pylori, the presence of mild/moderate and severe CAG was associated with a 6.4-fold (1.3–31.0) and an 11.8-fold (3.1–45.4) increase of gastric cancer incidence, respectively. The results of this prospective population-based cohort study may contribute relevant evidence to the ongoing research of H. pylori-related cancers. The results may furthermore enhance the empirical basis for risk stratification among H. pylori-infected people and for recommendations regarding H. pylori screening and treatment among older adults in a Western population.     

Occupational exposures and risk of esophageal and gastric cardia cancers among male Swedish construction workers

Objective: The rising incidence and the strong male predominance among patients with esophageal and gastric cardia adenocarcinoma remain unexplained. We hypothesized that occupational airborne exposures in a traditional male dominated industry might contribute to these observations.Methods: A prospective, large cohort study of Swedish construction workers was linked to the Swedish population-based registers of Cancer, Causes of Death and Total Population. 260,052 men were followed from 1971 through 2000. Industrial hygienists assessed specific exposures for 200 job titles, and occupational airborne exposures were analyzed separately and combined. Incidence rate ratios (IRR), with 95% confidence intervals (CI), were estimated in multivariable Cox regression models adjusted for attained age, calendar period, smoking status and body mass.Results: We found positive associations between high exposure to asbestos (IRR 4.5 [95% CI 1.4–14.3]) and cement dust (IRR 3.8 [95% CI 1.5–9.6]) and risk of esophageal adenocarcinoma. Associations were seen between high exposure to asphalt fumes (IRR 2.3 [95% CI 1.0–5.3]) and wood dust (IRR 4.8 [95% CI 1.2–19.4]) and risk of cardia adenocarcinoma. No consistent associations regarding esophageal squamous-cell carcinoma were found.Conclusions: Exposure to asbestos and cement dust may be risk factors for esophageal adenocarcinoma, and exposure to asphalt fumes and wood dust may increase the risk of cardia adenocarcinoma. However, these associations cannot explain the major sex differences or the increasing incidence trends of these tumors.     

Genetic variants at 8q24 are associated with risk of esophageal squamous cell carcinoma in a Chinese population

Esophageal cancer and gastric cancer have shared risk factors and inherited susceptibility. Recent genome‐wide association studies have identified multiple genetic loci associated with gastric cancer risk, which may also involve in the development of esophageal cancer. Herein, we evaluated the relationship of gastric cancer risk‐related variants at 1q22, 3q13.3, 5p13.1, and 8q24 with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population with a case–control study (2139 cases and 2273 controls). We found that the T allele of rs2294008, an intronic variant of the PSCA gene at 8q24 that was previously associated with an increased risk of gastric cancer, was inversely associated with a decreased risk of ESCC (odds ratio = 0.90; 95% confidence interval, 0.81–0.99; P = 0.034). Of interest, the association of rs2294008 with ESCC was consistent with that observed in esophageal adenocarcinoma and ESCC in Caucasian populations. However, no significant associations were observed for the other three variants at 1q22 (rs4072037), 3q13.31 (rs9841504), and 5p13.1 (rs13361707). Our findings suggest that the susceptibility locus of PSCA at 8q24 may be a double‐edged sword, as modulator between the carcinogenesis processes of stomach and esophagus.