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.     

Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas

Objectives Alcohol increases esophageal squamous carcinoma risk but has been less consistently associated with esophageal adenocarcinoma. Alcohol dehydrogenase catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a carcinogen. The alcohol dehydrogenase gene has several polymorphisms which may lead to faster conversion of ethanol to acetaldehyde, which may increase cancer risk. Methods We undertook a study to examine whether a common polymorphism in the alcohol dehydrogenase 3 gene was associated with a higher risk of esophageal adenocarcinoma using data and biological samples collected for the Esophageal and Gastric Cancer Study (n = 114 esophageal and gastric cardia adenocarcinoma, n = 60 non-cardia gastric carcinoma, n = 23 cases of esophageal squamous cell carcinoma and 160 controls). Results Individuals homozygous for ADH ₃ ^1–1 had a higher risk of each tumor type compared to individuals who had ADH ₃ ^2–2 or ADH ₃ ^1–2 genotype (OR = 1.7, 95% CI = 1.0–2.9 for esophageal and gastric cardia adenocarcinomas; OR = 1.7, 95% CI = 0.7–4.3 for esophageal squamous cell carcinoma; and OR = 2.8, 95% CI = 1.5–5.1 for non-cardia gastric cancer). The elevation in risk from homozygosity of the ADH ₃ ¹ allele was seen in drinkers and nondrinkers, although the risk estimate was only significant for drinkers, particularly of liquor. Conclusion These data suggest ADH3 genotype may be associated with risk of esophageal and gastric cardia adenocarcinomas. Janet B. Schoenberg, Retired.     

Cigarette smoking, body mass index, gastro-esophageal reflux disease, and non-steroidal anti-inflammatory drug use and risk of subtypes of esophageal and gastric cancers by P53 overexpression

A number of risk factors for esophageal and gastric cancers have emerged, yet little is known whether risk factors map to molecular tumor markers such as overexpression of the tumor suppressor TP53. Using a US multicenter, population-based case–control study (170 cases of esophageal adenocarcinomas, 147 gastric cardia adenocarcinomas, 220 non-cardia gastric adenocarcinomas, and 112 esophageal squamous cell carcinomas), we examined whether the risk associated with cigarette smoking, body mass index (BMI), gastroesophageal reflux disease (GERD), and non-steroidal anti-inflammatory drug (NSAID) use varied by P53 overexpression. We defined P53 overexpression through immunohistochemistry of paraffin-embedded tumor tissues, using cutpoints based on percent of cells positive. Polytomous logistic regression was used to assess differences between each case group (defined by tumor subtype and P53 expression) and the control group by risk factors. The proportion of cases overexpressing P53 by tumor subtype was 72% for esophageal adenocarcinoma, 69% for gastric cardia adenocarcinoma, 52% for non-cardia gastric adenocarcinoma, and 67% for esophageal squamous cell carcinoma. For most tumor subtypes, we found little difference in risk factors by tumor P53 overexpression. For non-cardia gastric cancer however, an association with cigarette smoking was suggested for tumors that do not overexpress P53, whereas larger BMI was related to adenocarcinomas that overexpress P53 versus no overexpression. Overall, this study did not find a clear relationship between P53 protein overexpression and the known risk factors for subtypes of esophageal and gastric cancers. Further research on these tumors is needed to identify molecular markers associated with variations in the risk factor profiles.     

Prospective study of tooth loss and incident esophageal and gastric cancers in China

Objective: To determine the association between tooth loss and the risk of developing esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, or gastric non-cardia adenocarcinoma in a prospective study. Methods: Cox proportional hazards regression was used to examine these associations in a 28,868-person cohort followed prospectively for 5.25 years. The baseline questionnaire included questions regarding tooth loss, and individuals reporting lost teeth had their teeth counted by study personnel. The analytic cohort included 620 esophagus, 431 gastric cardia, and 102 gastric non-cardia cancer cases. Results: Tooth loss was associated with a significantly elevated risk of developing all three cancers. When examined as median splits, tooth loss was associated with a relative risk (RR) (95% confidence interval, CI) of 1.3 (1.1–1.6) in the esophagus, 1.3 (1.0–1.6) in the gastric cardia, and 1.8 (1.1–3.0) in the gastric non-cardia. Further analysis demonstrated that this increased risk was most strongly associated with the loss of the first few teeth and was primarily confined to the younger members of our cohort. Conclusions: In this cohort tooth loss increased the risk of developing upper gastrointestinal cancer. We hypothesize that this may be related to alterations in oral bacterial flora and subsequent increases in the in-vivo production of carcinogens such as nitrosamines.     

Family history of cancer and risk of esophageal and gastric cancers in the United States

The worldwide rates for histology- and subsite-specific types of esophageal and gastric cancer reveal strikingly divergent patterns. The contribution of environmental and genetic factors has been explored in several high-incidence areas, but data on genetic influences are scarce for Western countries. Using data from a multicenter, population-based, case-control study on 1,143 cases and 695 controls in the United States, we evaluated whether a family history of digestive or other cancers was associated with an increased risk of esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261) or non-cardia gastric adenocarcinoma (n = 368). After adjusting for other risk factors, individuals reporting a family history of digestive cancers experienced no increased risk of either type of esophageal cancer but they were prone to adenocarcinomas of the gastric cardia [odds ratio (OR) = 1.34, 95% confidence interval (CI) 0.91-1.97] and non-cardia segments (OR =1.46, 95% CI 1.03-2.08). This familial tendency, particularly for non-cardia gastric tumors, was largely explained by an association with family history of stomach cancer (OR = 2.52, 95% CI 1.50-4.23). In addition, family history of breast cancer was associated with increased risks of esophageal adenocarcinoma (OR = 1.74, 95% CI 1.07-2.83) and non-cardia gastric adenocarcinoma (OR = 1.76, 95% CI 1.09-2.82). Also seen were non-significant familial associations of esophageal squamous-cell cancer with prostate cancer as well as non-cardia gastric cancer with leukemia and brain tumors, though these relationships must be interpreted with caution. Our data point to the role of familial susceptibility to gastric cancer, but not to any form of esophageal cancer, in the United States.     

A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinomas of the stomach and esophagus (United States)

Objectives: Since the 1970s incidence rates for esophageal and gastric cardia adenocarcinomas have risen substantially, particularly among white males in the United States. Reasons for the increase of these tumor types are not well understood. We sought to determine the role of smoking, alcohol use, and body size characteristics in the etiology of esophageal, gastric cardia, and distal gastric adenocarcinomas. Materials and methods: A population-based case–control study that included Whites, African-Americans, Latinos and Asian-Americans diagnosed with incident esophageal (n = 222), gastric cardia (n = 277), and distal gastric adenocarcinomas (n = 443), and 1356 control subjects was conducted in Los Angeles County. Unconditional logistic regression was used to calculate odds ratios (ORs), as an estimate of the relative risk, and corresponding 95% confidence intervals (CIs) for the three tumor types of interest. Results: After adjustment for age, gender, race, birthplace, and education, current cigarette smoking was a significant risk factor for all tumor types; the association was strongest for esophageal adenocarcinomas (OR = 2.80, 95% CI = 1.8–4.3), intermediate for gastric cardia adenocarcinomas (OR = 2.12, 95% CI = 1.5–3.1), and weaker for distal gastric adenocarcinomas (OR = 1.50, 95% CI = 1.1–2.1). For esophageal adenocarcinomas only, cigarette smoking had a long-lasting deleterious effect, even 20 years after smoking cessation. Alcohol use was not associated with an increased risk of these tumor types. Risks of esophageal and gastric cardia adenocarcinomas also increased statistically significantly in a dose-dependent manner with increasing body mass index measured at ages 20 and 40 years and recently. The positive associations with smoking and body mass index were generally consistent when evaluated separately for Whites, non-Whites, males, and females. Conclusions: Cigarette smoking and high body mass index are significant, independent risk factors for esophageal and gastric cardia adenocarcinomas. Studies designed to understand the mechanisms whereby smoking and high body mass influence these tumor types are needed.     

Food group intake and risk of subtypes of esophageal and gastric cancer

Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non-cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multicenter, population-based case-control study in Connecticut, New Jersey and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI = 1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73) and noncardia gastric adenocarcinoma (OR = 1.39, 95% CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and noncardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High-fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high-fat dairy was associated with increased risk of gastric cardia adenocarcinoma.     

Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer

Objective: The incidence of esophageal adenocarcinoma has risen rapidly in the past two decades, for unknown reasons. The goal of this analysis was to determine whether gastroesophageal reflux disease (GERD) or the medications used to treat it are associated with an increased risk of esophageal or gastric cancer, using data from a large population-based case–control study. Methods: Cases were aged 30–79 years, newly diagnosed with esophageal adenocarcinoma (n=293), esophageal squamous cell carcinoma (n=221), gastric cardia adenocarcinoma (n=261), or non-cardia gastric adenocarcinoma (n=368) in three areas with population-based tumor registries. Controls (n=695) were chosen by random digit dialing and from Health Care Financing Administration rosters. Data were collected using an in-person structured interview. Results: History of gastric ulcer was associated with an increased risk of non-cardia gastric adenocarcinoma (OR 2.1, 95% CI 1.4–3.2). Risk of esophageal adenocarcinoma increased with frequency of GERD symptoms; the odds ratio in those reporting daily symptoms was 5.5 (95% CI 3.2–9.3). Ever having used H₂ blockers was unassociated with esophageal adenocarcinoma risk (OR 0.9, 95% CI 0.5–1.5). The odds ratio was 1.3 (95% CI 0.6–2.8) in long-term (4 or more years) users, but increased to 2.1 (95% CI 0.8–5.6) when use in the 5 years prior to the interview was disregarded. Risk was also modestly increased among users of antacids. Neither GERD symptoms nor use of H₂ blockers or antacids was associated with risk of the other three tumor types. Conclusions: Individuals with long-standing GERD are at increased risk of esophageal adenocarcinoma, whether or not the symptoms are treated with H₂blockers or antacids.     

Abdominal obesity and the risk of esophageal and gastric cardia carcinomas

BACKGROUND: Esophageal adenocarcinoma is rapidly increasing in incidence. Body mass index (BMI) is a risk factor, but its distribution does not reflect the demographic distribution of the cancer (which is highest among White men). Abdominal obesity patterns may explain this discordance, but no studies exist to date. METHODS: Nested case-control study within 206,974 members of the Kaiser Permanente multiphasic health checkup cohort; subjects received detailed questionnaires, a standardized examination including BMI and anthropometric measurements, and follow-up of esophageal and cardia cancers using registry data. RESULTS: 101 incident esophageal adenocarcinomas, 105 cardia adenocarcinomas, and 144 esophageal squamous cell carcinomas were detected (BMI data available for all cases; abdominal measurements for a subset). Increasing abdominal diameter was strongly associated with an increased risk of esophageal adenocarcinoma [odds ratio (OR), 3.47; 95% confidence interval (95% CI), 1.29-9.33; abdominal diameter, > or =25 versus <20 cm]. Adjustment for BMI did not diminish this association (BMI-adjusted OR, 4.78; 95% CI, 1.14-20.11). The association was also not diminished by adjustment for gastroesophageal reflux-type symptoms, although reflux-type symptoms were separately associated with both abdominal diameter and cancer risk. Abdominal diameter was not associated with the risk of cardia adenocarcinomas (OR, 1.28; 95% CI, 0.38-4.25; diameter, > or =25 versus <20 cm) or esophageal squamous cell carcinomas (OR, 0.78; 95% CI, 0.32-1.92). CONCLUSIONS: Increasing abdominal diameter was associated with an increased risk of esophageal adenocarcinoma, independent of BMI. Cancer risk was not substantially mediated through gastroesophageal reflux-type symptoms, although symptoms may imperfectly measure reflux severity. Given abdominal obesity is more common among males, these findings suggest that increases in obesity may disproportionately increase the risk of esophageal adenocarcinoma in males.     

A prospective study of BMI and risk of oesophageal and gastric adenocarcinoma

The incidence of oesophageal adenocarcinoma (EADC) is rapidly increasing in Western countries and obesity is thought to be a major risk factor. We examined the association between BMI and EADC, gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma in a cohort of approximately 500,000 people in the United States (US). We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) with control for many potential confounders. We found that compared to people with a BMI of 18.5-25kg/m2, a BMI > or = 35 was associated with significantly increased risk of EADC, HR (95% CI)=2.27 (1.44-3.59) and gastric cardia adenocarcinoma 2.46 (1.60-3.80), but not gastric non-cardia adenocarcinoma 0.84 (0.50-1.42). Using non-linear models, we found that higher BMI was associated with increased risk of EADC even within the normal BMI. Increased adiposity was associated with higher risk of EADC even within the normal weight range.     

Diabetes and risk of esophageal and gastric adenocarcinomas

Diabetes has been consistently associated with an increased risk of liver, pancreas and endometrial cancer and has been implicated as a risk factor for esophageal and gastric cancers, although this association has been less well studied. We sought to determine the role of diabetes in the etiology of esophageal, gastric cardia and distal gastric adenocarcinomas (DGAs). This analysis included patients with esophageal adenocarcinoma (EA) (n = 209), gastric cardia adenocarcinoma (GCA) (n = 257) and DGA (n = 382), and 1,309 control participants from a population-based case-control study conducted in Los Angeles County. The study included non-Hispanic whites, African Americans, Hispanics and Asian Americans. The association of diabetes with the three tumor types was estimated using polytomous logistic regression. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated. Nine percent of control participants and 13% of the case patients reported a history of diabetes. After adjustment for age, gender, race, birthplace, education, cigarette smoking status and body mass index, diabetes was associated with an increased risk of EA (OR, 1.48; 95% CI, 0.94-2.32; p = 0.089) and DGA (OR, 1.47; 95% CI, 1.01-2.15; p = 0.045), but was not associated with risk of GCA (OR, 0.96; 95% CI, 0.59-1.55; p = 0.87). However, the association between diabetes and risk of DGA was statistically significant only among patients for whom we interviewed their next of kin. Our study further investigated the association between diabetes and adenocarcinomas of the esophagus and distal stomach.     

Hiatal hernia,reflux symptoms,body size,and risk of esophageal and gastric adenocarcinoma

BACKGROUND: Since the 1970s, incidence rates of esophageal and gastric cardia adenocarcinoma have risen substantially. Reasons for the increasing trends are not well understood. METHODS: A population-based, case-control study that included esophageal adenocarcinomas (n = 222), gastric cardia adenocarcinomas (n = 277), distal gastric adenocarcinomas (n = 443), and 1356 controls was conducted in Los Angeles County. Unconditional logistic regression was used to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the 3 tumor types. RESULTS: After adjustment for demographic factors, smoking, and body size, both hiatal hernia and reflux symptoms emerged as significant independent risk factors. Risk of esophageal adenocarcinoma was increased 3-fold (adjusted OR, 3.61; 95% CI, 2.49-5.25) among those who had reflux symptoms but did not have hiatal hernia, 6-fold (adjusted OR, 5.85; 95% CI, 3.18-10.75) among those who had hiatal hernia but did not have reflux symptoms, and 8-fold (adjusted OR, 8.11; 95% CI, 4.75-13.87) among those who had both reflux symptoms and hiatal hernia. A similar risk pattern was found in relation to history of hiatal hernia and other reflux conditions. A more modest but still significant risk pattern was observed for gastric cardia adenocarcinoma. Among control subjects, there was a significant and positive association between increasing body mass index and history of hiatal hernia and/or reflux symptoms. CONCLUSIONS: Hiatal hernia, in combination with other reflux conditions and symptoms, was associated strongly with the risk of esophageal adenocarcinoma. These associations were more modest for gastric cardia adenocarcinomas. A significant and positive association between body size and history of hiatal hernia/reflux symptoms also was observed.     

Opium: An emerging risk factor for gastric adenocarcinoma

Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case‐control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed‐location adenocarcinomas) and 613 matched controls. Detailed information on long‐term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9–5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose‐response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.3–8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance.     

Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women

BackgroundAdenocarcinomas of the upper gastrointestinal tract (UGI) show remarkable male predominance. As smoking is a well-established risk factor, we investigated the role of tobacco smoking in the male predominance of UGI adenocarcinomas in the United States NIH-AARP Diet and Health Study.MethodA questionnaire was completed by 281,422 men and 186,133 women in 1995–1996 who were followed until 31st December 2003. Incident UGI adenocarcinomas were identified by linkage to state cancer registries. We present age-standardised cancer incidence rates per 100,000-person years and male/female ratios (M/F) calculated from age-adjusted Cox proportional hazards models, both with 95% confidence intervals (CI).ResultsAfter 2013,142-person years follow-up, 338 adenocarcinomas of the oesophagus, 261 of gastric cardia and 222 of gastric non-cardia occurred in men. In women, 23 tumours of oesophagus, 36 of gastric cardia and 88 of gastric non-cardia occurred in 1351,958-person years follow-up. The age-standardised incidence rate of all adenocarcinoma sites was 40.5 (37.8–43.3) and 11.0 (9.2–12.8) in men and women, respectively. Among smokers, the M/F of all UGI adenocarcinomas was 3.4 (2.7–4.1), with a M/F of 7.3 (4.6–11.7) for tumours in oesophagus, 3.7 (2.5–5.4) for gastric cardia and 1.7 (1.2–2.3) for gastric non-cardia. In non-smokers, M/F ratios were 14.2 (5.1–39.5) for oesophagus, 6.1 (2.6–14.7) for gastric cardia and 1.3 (0.8–2.0) for gastric non-cardia. The overall M/F ratio was 3.0 (2.2–4.3).ConclusionThe male predominance was similar in smokers and non-smokers for these cancer sites. These results suggest that the male predominance of upper GI adenocarcinomas cannot be explained by differences in smoking histories.     

Red and processed meat consumption and the risk of esophageal and gastric cancer subtypes in The Netherlands Cohort Study

BackgroundProspective data on red and processed meat in relation to risk of subtypes of esophageal and gastric cancer are scarce. We present analyses of association between red and processed meat and the risk of esophageal and gastric cancer subtypes within The Netherlands Cohort Study on Diet and Cancer.Design120 852 individuals aged 55–69 years were recruited in 1986, and meat intake was assessed using a 150-item food frequency questionnaire. After 16.3 years of follow-up, 107 esophageal squamous cell carcinomas, 145 esophageal adenocarcinomas, 163 gastric cardia adenocarcinomas, 489 gastric non-cardia adenocarcinomas, and 3923 subcohort members were included in a case–cohort analysis.ResultsProcessed as well as red meat intake was positively associated with esophageal squamous cell carcinoma in men. Hazard ratios for highest versus lowest quintile of processed and red meat were 3.47 [95% confidence intervals (CI): 1.21–9.94; P for trend: 0.04] and 2.66 (95% CI: 0.94–7.48; P for trend: 0.06), respectively. No association was seen for adenocarcinomas or gastric cancer subtypes or for any of the four subtypes among women.ConclusionOur findings suggest that red and processed meat consumption is associated with increased risk of esophageal squamous cell carcinoma in men but not with cancers of other esophageal and gastric subtypes.     

Prospective study of serum retinol, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin and esophageal and gastric cancers in China

Objective: This study examined the relationship between pretrial serum concentrations of retinol, -carotene, -cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer. Methods: We used a stratified case–cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models. Results: Median values in our cohort were low for serum retinol (33.6 g/dl), -carotene (4.3 g/dl), and -cryptoxanthin (3.5 g/dl) , but were high for lutein/zeaxanthin (40.0 g/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83–0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63–0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31–0.96). For -cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76–1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0–1.3) with increasing concentration of serum lutein/zeaxanthin. Conclusions: In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.     

Body mass index and esophageal and gastric cancer: A pooled analysis of 10 population-based cohort studies in Japan

The effect of body mass index (BMI) on esophageal and gastric carcinogenesis might be heterogeneous, depending on subtype or subsite. However, findings from prospective evaluations of BMI associated with these cancers among Asian populations have been inconsistent and limited, especially for esophageal adenocarcinoma and gastric cardia cancer. We performed a pooled analysis of 10 population-based cohort studies to examine this association in 394,247 Japanese individuals. We used Cox proportional hazards regression to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs), then pooled these estimates to calculate summary HRs with a random effects model. During 5,750,107 person-years of follow-up, 1569 esophageal cancer (1038 squamous cell carcinoma and 86 adenocarcinoma) and 11,095 gastric (728 cardia and 5620 noncardia) cancer incident cases were identified. An inverse association was observed between BMI and esophageal squamous cell carcinoma (HR per 5-kg/m² increase 0.57, 95% CI 0.50–0.65), whereas a positive association was seen in gastric cardia cancer (HR 1.15, 95% CI 1.00–1.32). A nonsignificant and significant positive association for overweight or obese (BMI ≥25 kg/m²) relative to BMI <25 kg/m² was observed with esophageal adenocarcinoma (HR 1.32, 95% CI 0.80–2.17) and gastric cardia cancer (HR 1.24, 95% CI 1.05–1.46), respectively. No clear association with BMI was found for gastric noncardia cancer. This prospective study—the largest in an Asian country—provides a comprehensive quantitative estimate of the association of BMI with upper gastrointestinal cancer and confirms the subtype- or subsite-specific carcinogenic impact of BMI in a Japanese population.     

Intakes of folate,methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study

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.     

A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma

BackgroundThe incidence rates of esophageal and gastric cardia adenocarcinoma (EGCA) have increased over recent years in several countries, and overweight/obesity has been suggested to play a major role in these trends. In fact, higher body mass index (BMI) has been positively associated with EGCA in several studies.Material and methodsWe conducted a meta-analysis of case–control and cohort studies on the BMI and EGCA updated to March 2011. We estimated overall relative risks (RRs) and 95% confidence intervals (CI) for BMI between 25 and 30 and BMI ≥ 30 kg/m², when compared with normo-weight subjects, using random-effects models.ResultsWe identified 22 studies, including almost 8000 EGCA cases. The overall RR was 1.71 (95% CI 1.50–1.96) for BMI between 25 and 30, and was 2.34 (95% CI 1.95–2.81) for BMI ≥ 30 kg/m². The continuous RR for an increment of 5 kg/m² of BMI was 1.11 (95% CI 1.09–1.14). The association was stronger for esophageal adenocarcinoma (RR for BMI ≥ 30 kg/m² = 2.73, 95% CI 2.16–3.46) than for gastric cardia adenocarcinoma (RR for BMI ≥ 30 kg/m² = 1.93, 95% CI 1.52–2.45). No substantial differences emerged across strata of sex and geographic areas.ConclusionOverweight and obesity are strongly related to EGCA, particularly to espophageal adenocarcinoma.     

Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China

In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case-cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15-2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies.