Reproductive factors, hormonal interventions, and gastric cancer risk in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Gastric cancer incidence is higher in men, and a protective hormone-related effect in women is postulated. We aimed to investigate and quantify the relationship in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 2,084 cases and 7,102 controls from 11 studies in seven countries were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) assessing associations of key reproductive factors and menopausal hormone therapy (MHT) with gastric cancer were estimated by pooling study-specific ORs using random-effects meta-analysis. RESULTS: A duration of fertility of ≥ 40 years (vs. < 20), was associated with a 25% lower risk of gastric cancer (OR = 0.75; 95% CI: 0.58-0.96). Compared with never use, ever, 5-9 years and ≥ 10 years use of MHT in postmenopausal women, showed ORs of 0.73 (95% CI: 0.58-0.92), 0.53 (95% CI: 0.34-0.84) and 0.71 (95% CI: 0.50-1.00), respectively. The associations were generally similar for anatomical and histologic subtypes. CONCLUSION: Our results support the hypothesis that reproductive factors and MHT use may lower the risk of gastric cancer in women, regardless of anatomical or histologic subtypes. Given the variation in hormones over the lifespan, studies should address their effects in premenopausal and postmenopausal women. Furthermore, mechanistic studies may inform potential biological processes.

Mushroom consumption and risk of gastric cancer: a pooled analysis within the stomach cancer pooling project and a combined meta-analysis with other observational studies.

Edible mushrooms have high concentrations of vitamins and minerals. They are considered 'functional foods' for their disease-prevention properties. Mushroom consumption may reduce the risk of gastric cancer, the fifth most common cancer worldwide. We investigated the association between mushroom consumption and gastric cancer risk in a pooled analysis within the Stomach Cancer Pooling (StoP) Project and in a meta-analysis that also included previously published studies. A total of 3900 gastric cancer cases and 7792 controls from 11 studies were included in the StoP analysis. Mushroom consumption was measured using food frequency questionnaires. Higher mushroom consumption was associated with a lower risk of gastric cancer [relative risk (RR) for the highest vs. lowest consumption categories, 0.82; 95% confidence interval (CI), 0.71-0.95]. The corresponding RRs were 0.59 (95% CI, 0.26-1.33) in a meta-analysis of four previously published studies and 0.77 for all studies combined (95% CI, 0.63-0.95; n = 15 studies). In geographic subgroup analysis, the pooled risk in Western Pacific countries was (RR, 0.59; 95% CI, 0.40-0.87; n = 6). The stronger effect in Asian countries may reflect high level of antioxidants in mushroom species consumed in Asia.

The mediating role of combined lifestyle factors on the relationship between education and gastric cancer in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: The causal pathway between high education and reduced risk of gastric cancer (GC) has not been explained. The study aimed at evaluating the mediating role of lifestyle factors on the relationship between education and GC METHODS: Ten studies with complete data on education and five lifestyle factors (smoking, alcohol drinking, fruit and vegetable intake, processed meat intake and salt consumption) were selected from a consortium of studies on GC including 4349 GC cases and 8441 controls. We created an a priori score based on the five lifestyle factors, and we carried out a counterfactual-based mediation analysis to decompose the total effect of education on GC into natural direct effect and natural indirect effect mediated by the combined lifestyle factors. Effects were expressed as odds ratios (ORs) with a low level of education as the reference category. RESULTS: The natural direct and indirect effects of high versus low education were 0.69 (95% CI: 0.62-0.77) and 0.96 (95% CI: 0.95-0.97), respectively, corresponding to a mediated percentage of 10.1% (95% CI: 7.1-15.4%). The mediation effect was limited to men. CONCLUSIONS: The mediation effect of the combined lifestyle factors on the relationship between education and GC is modest. Other potential pathways explaining that relationship warrants further investigation.

Tea consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling (StoP) Project consortium.

BACKGROUND: Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer. RESULTS: Compared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84). CONCLUSION: Our results indicate a weak inverse association between tea consumption and gastric cancer.

Salt intake and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

PURPOSE: Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project. METHODS: Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI). RESULTS: Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25-2.03), always using table salt (aOR 1.33, 95% CI 1.16-1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01-1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82-1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics. CONCLUSION: Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake.

"True" Helicobacter pylori infection and non-cardia gastric cancer: A pooled analysis within the Stomach Cancer Pooling (StoP) Project.

BACKGROUND: Helicobacter pylori is the most important risk factor for non-cardia gastric cancer (NCGC); however, the magnitude of the association varies across epidemiological studies. This study aimed to quantify the association between H. pylori infection and NCGC, using different criteria to define infection status. METHODS: A pooled analysis of individual-level H. pylori serology data from eight international studies (1325 NCGC and 3121 controls) from the Stomach Cancer Pooling (StoP) Consortium was performed. Cases and controls with a negative H. pylori infection status were reclassified as positive considering the presence of anti-Cag A antibodies, gastric atrophy, or advanced stage at diagnosis, as available and applicable. A two-stage approach was used to pool study-specific adjusted odds ratios (OR), and 95% confidence intervals (95% CI). A meta-analysis of published prospective studies assessing H. pylori seropositivity in NCGCs was conducted. RESULTS: The OR for the association between serology-defined H. pylori and NCGC was 1.45 (95% CI: 0.87-2.42), which increased to 4.79 (95% CI: 2.39-9.60) following the reclassification of negative H. pylori infection. The results were consistent across strata of sociodemographic characteristics, clinical features and lifestyle factors, though significant differences were observed according to geographic region-a stronger association in Asian studies. The pooled risk estimates from the literature were 3.01 (95% CI: 2.22-4.07) for ELISA or EIA and 9.22 (95% CI: 3.12-27.21) for immunoblot or multiplex serology. CONCLUSION: The NCGC risk estimate from StoP based on the reclassification of H. pylori seronegative individuals is consistent with the risk estimates obtained from the literature. Our classification algorithm may be useful for future studies.

Identifying the Profile of Helicobacter pylori-Negative Gastric Cancers: A Case-Only Analysis within the Stomach Cancer Pooling (StoP) Project.

BACKGROUND: The prevalence of Helicobacter pylori-negative gastric cancer (HpNGC) can be as low as 1%, when infection is assessed using more sensitive tests or considering the presence of gastric atrophy. HpNGC may share a high-risk profile contributing to the occurrence of cancer in the absence of infection. We estimated the proportion of HpNGC, using different criteria to define infection status, and compared HpNGC and positive cases regarding gastric cancer risk factors. METHODS: Cases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data on H. pylori infection status determined by serologic test were included. HpNGC was reclassified as positive (eight studies) when cases presented CagA markers (four studies), gastric atrophy (six studies), or advanced stage at diagnosis (three studies), and were compared with positive cases. A two-stage approach (random-effects models) was used to pool study-specific prevalence and adjusted odds ratios (OR). RESULTS: Among non-cardia cases, the pooled prevalence of HpNGC was 22.4% (n = 166/853) and decreased to 7.0% (n = 55) when considering CagA status; estimates for all criteria were 21.8% (n = 276/1,325) and 6.6% (n = 97), respectively. HpNGC had a family history of gastric cancer more often [OR = 2.18; 95% confidence interval (CI), 1.03-4.61] and were current smokers (OR = 2.16; 95% CI, 0.52-9.02). CONCLUSION: This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives. IMPACT: Our results support that H. pylori infection is present in most non-cardia gastric cancers, and suggest that HpNGC may have distinct patterns of exposure to other risk factors.

Coffee consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling Project consortium.

OBJECTIVE: This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls. METHODS: A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer. RESULTS: Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only. CONCLUSIONS: These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.

Fruits and vegetables intake and gastric cancer risk: A pooled analysis within the Stomach cancer Pooling Project.

A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure-response relations, including linear and nonlinear associations, were modeled using one- and two-order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95% CI: 0.64-0.90), noncitrus fruits (OR: 0.86, 95% CI: 0.73-1.02), vegetables (OR: 0.68, 95% CI: 0.56-0.84), and fruits and vegetables (OR: 0.61, 95% CI: 0.49-0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure-response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95% CI: 0.57-0.73 for six portions), noncitrus fruits (OR: 0.71, 95% CI: 0.61-0.83 for six portions) and vegetables (OR: 0.51, 95% CI: 0.43-0.60 for 10 portions). A protective effect of all fruits, noncitrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer.

Occupational exposures and odds of gastric cancer: a StoP project consortium pooled analysis.

BACKGROUND: Gastric cancer pathogenesis represents a complex interaction of host genetic determinants, microbial virulence factors and environmental exposures. Our primary aim was to determine the association between occupations/occupational exposures and odds of gastric cancer. METHODS: We conducted a pooled-analysis of individual-level data harmonized from 11 studies in the Stomach cancer Pooling Project. Multivariable logistic regression was used to estimate the odds ratio (OR) of gastric cancer adjusted for relevant confounders. RESULTS: A total of 5279 gastric cancer cases and 12 297 controls were analysed. There were higher odds of gastric cancer among labour-related occupations, including: agricultural and animal husbandry workers [odds ratio (OR) 1.33, 95% confidence interval (CI): 1.06-1.68]; miners, quarrymen, well-drillers and related workers (OR 1.70, 95% CI: 1.01-2.88); blacksmiths, toolmakers and machine-tool operators (OR 1.41, 95% CI: 1.05-1.89); bricklayers, carpenters and construction workers (OR 1.30, 95% CI: 1.06-1.60); and stationary engine and related equipment operators (OR 6.53, 95% CI: 1.41-30.19). The ORs for wood-dust exposure were 1.51 (95% CI: 1.01-2.26) for intestinal-type and 2.52 (95% CI: 1.46-4.33) for diffuse-type gastric cancer. Corresponding values for aromatic amine exposure were 1.83 (95% CI: 1.09-3.06) and 2.92 (95% CI: 1.36-6.26). Exposure to coal derivatives, pesticides/herbicides, chromium, radiation and magnetic fields were associated with higher odds of diffuse-type, but not intestinal-type gastric cancer. CONCLUSIONS: Based on a large pooled analysis, we identified several occupations and related exposures that are associated with elevated odds of gastric cancer. These findings have potential implications for risk attenuation and could be used to direct investigations evaluating the impact of targeted gastric cancer prevention/early detection programmes based on occupation.

Meat intake and risk of gastric cancer in the Stomach cancer Pooling (StoP) project.

The consumption of processed meat has been associated with noncardia gastric cancer, but evidence regarding a possible role of red meat is more limited. Our study aims to quantify the association between meat consumption, namely white, red and processed meat, and the risk of gastric cancer, through individual participant data meta-analysis of studies participating in the "Stomach cancer Pooling (StoP) Project". Data from 22 studies, including 11,443 cases and 28,029 controls, were used. Study-specific odds ratios (ORs) were pooled through a two-stage approach based on random-effects models. An exposure-response relationship was modeled, using one and two-order fractional polynomials, to evaluate the possible nonlinear association between meat intake and gastric cancer. An increased risk of gastric cancer was observed for the consumption of all types of meat (highest vs. lowest tertile), which was statistically significant for red (OR: 1.24; 95% CI: 1.00-1.53), processed (OR: 1.23; 95% CI: 1.06-1.43) and total meat (OR: 1.30; 95% CI: 1.09-1.55). Exposure-response analyses showed an increasing risk of gastric cancer with increasing consumption of both processed and red meat, with the highest OR being observed for an intake of 150 g/day of red meat (OR: 1.85; 95% CI: 1.56-2.20). This work provides robust evidence on the relation between the consumption of different types of meat and gastric cancer. Adherence to dietary recommendations to reduce meat consumption may contribute to a reduction in the burden of gastric cancer.

Secular trends in cancer mortality among Japanese immigrants in the state of São Paulo, Brazil, 1979-2001.

We investigated secular trends in cancer mortality among first-generation Japanese-Brazilians in the state of São Paulo between 1979 and 2001. Results were compared with those for Japanese living in Japan and Brazilians living in the state of São Paulo. We used mortality data for three periods, 1979-1981, 1989-1991, and 1999-2001, and population data from Brazilian censuses in 1980, 1991, and 2000 for Japanese-Brazilians. Available mortality and population data for Japanese living in Japan and Brazilians living in the state of São Paulo corresponding to those for Japanese-Brazilians were obtained. Age-standardized mortality rates for Japanese-Brazilians and standardized mortality ratios based on mortality of Japanese living in Japan in 1980 for the three different periods and populations were calculated. We observed a decreasing trend for stomach cancer and increasing trends for colon, breast and prostate cancer over the 20 years in all three populations. Standardized mortality ratios for stomach cancer in Japanese-Brazilians declined to approximately those of Japanese living in Japan. Although standardized mortality ratios from colon, breast and prostate cancer in Japanese-Brazilians increased over the last 20 years, those for colon cancer were similar to the Japanese living in Japan whereas those for breast and prostate cancer (208 and 423 in 2000, respectively) appeared to be intermediate between those for Japanese living in Japan (152 and 208 in 2000, respectively) and Brazilians living in the state of São Paulo (281 and 536 in 2000, respectively). Standardized mortality ratios for liver and lung cancer increased in Japanese living in Japan over the last 20 years but no increasing trend was observed for Japanese-Brazilians, except for liver cancer in men, and standardized mortality ratios in Japanese-Brazilians seemed to be similar to the Brazilians living in the state of São Paulo. Secular trends in mortality confirm the relative importance of environment in the development of cancer.

Cancer mortality among Japanese immigrants and their descendants in the state of São Paulo, Brazil, 1999-2001.

BACKGROUND: Only a few studies on the mortality of Japanese immigrants have been conducted in Brazil despite a large population of Japanese immigrants and their different environment and lifestyle from Japanese living in Japan. METHODS: To compare cancer mortality between Japanese in Japan and Japanese immigrants or Brazilians in the state of São Paulo, Brazil, we obtained official death certificates registered during 1999-2001. The standardized mortality ratio (SMR) or the standardized proportional mortality ratio (SPMR) of major cancer sites was calculated for the first generation of Japanese immigrants to Brazil (Japan-born), their Brazil-born Japanese descendants, and native Brazilians using mortality data of Japanese in Japan as a standard. RESULTS: The SMRs of stomach and colorectal cancer did not differ between the Japan-born residents of Brazil and the native Japanese, but significantly low SMRs were found among the native Brazilians. Compared with the native Japanese, we observed significantly lower SMRs for liver, gallbladder and lung cancer and significantly higher SMRs for prostate, cervical, and brain and nervous system cancer among both the Japan-born residents of Brazil and the Brazilians. Generally, the SPMR results were similar to those of the SMRs. Significantly high SPMRs for breast and uterine cancer were found for both the Japan- and Brazil-born residents of Brazil, although the Japan-born residents had increased SMRs, but not significantly so. CONCLUSIONS: We confirmed the different cancer mortality pattern in the Japanese immigrants from that in Japanese in Japan, thus demonstrating the relative importance of the environment in the development of cancer.

Risk factors for stomach cancer in Brazil (II): a case-control study among Japanese Brazilians in São Paulo.

BACKGROUND: Although stomach cancer is the most frequent cancer among Japanese Brazilians, the risk factor of this cancer has not been investigated among them. METHODS: A case-control study was conducted among Japanese residents in the city of São Paulo. Ninety-six consecutive cases of histologically confirmed stomach cancer were matched to 192 controls admitted for non-neoplastic diseases or healthy volunteer (n = 80) by age (+/-5 years) and gender. The socio-demographic characteristics, personal and family medical history, lifetime history of tobacco use and dietary habits were probed using a structured questionnaire. RESULTS: Frequent consumption of beef was associated with increased risk: odds ratio (OR) = 4.0 and 95% confidence interval (CI) = 1.9-8.4 for daily consumption, OR = 2.1 and 95% CI = 1.0-4.3 for 3-4 days/week) when compared with the category of lower consumption (<3 days/week) after adjustment for country of birth (Japan or Brazil), showing a dose-response pattern (P for trend = 0.001). These ORs became higher after further adjusted for fruit consumption: OR = 4.4, 95% CI = 2.1-9.4 and OR = 2.4 and 95% CI = 1.1-5.0, respectively. Daily consumption of fruit was associated with a reduction in risk (OR = 0.5, 95% CI = 0.3-1.0) after adjustment for country of birth and became statistically significant further adjusted for beef consumption (OR = 0.4, 95% CI = 0.2-0.9). There were no statistically significant associations with smoking or any other factors tested. Although some attenuation was observed in beef consumption, the observed associations were similar after excluding volunteer controls. CONCLUSIONS: The introduction of the habit of daily beef consumption among Japanese immigrants and their descendants may be associated with stomach cancer risk. The protective effect of fruit consumption was confirmed in this population.

Risk factors for stomach cancer in Brazil (I): a case-control study among non-Japanese Brazilians in São Paulo.

BACKGROUND: Stomach cancer is an important health problem in Brazil, with an estimated 20 000 new cases per year and it was the most frequent cancer site in men and the third most frequent site in women in São Paulo in 1993. Nevertheless, there are no reports of analytical epidemiological study on stomach cancer in Brazil. METHODS: A hospital-based case-control study was conducted among Brazilian residents with a non-Japanese background in the city; 236 consecutive cases of histologically confirmed stomach cancer were matched to the same number of controls admitted for non-neoplastic diseases by age (+/-5 years) and gender. The socio-demographic characteristics, personal and family medical history, lifetime history of tobacco use and dietary habits were determined by interview using a structured questionnaire. RESULTS: Non-white race, lower educational background and lower family income were more frequent in stomach cancer patients. After adjustment for race and educational background, cigarette smoking, frequent use of oil and frequent consumption of egg were significantly associated with increased risk of stomach cancer, while frequent consumption of fruit and vegetables decreased the risk. These associations did not change substantially after mutual adjustment of the other variables. CONCLUSIONS: The present study confirmed that low socio-economic status, cigarette smoking and low consumption of fruit and vegetables were risk factors of stomach cancer in São Paulo, Brazil.

Características das doenças no idoso / Characteristics of diseases of the aged

Os autores se propöem a relatar as diferenças que ocorrem entre pacientes idosos e de outras faixas etárias no que se refere a manifestaçöes e doenças, alteraçöes nos exames complementares e resposta a drogas