The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 µg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85-1.56), and the OR100 µg/day = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

Aspirin but not statins is inversely related to gastric cancer with a duration-risk effect: Results from the Stomach Cancer Pooling Project Consortium.

BACKGROUND: Aspirin and statins have been suggested to have potential chemopreventive effects against gastric cancer (GC), although the results of previous studies have been inconsistent. This study therefore aimed to investigate the association between the use of aspirin and statins and GC. METHODS: A pooled analysis of seven case-control studies within the Stomach Cancer Pooling Project, including 3220 cases and 9752 controls, was conducted. Two-stage modeling analyses were used to estimate the association between aspirin and statin use and GC after adjusting for potential confounders. RESULTS: The pooled odds ratio (OR) of GC for aspirin users versus nonusers was 0.72 (95% confidence interval [CI], 0.54-0.95). The protective effect of aspirin appeared stronger in individuals without a GC family history (OR, 0.60; 95% CI, 0.37-0.95), albeit with borderline heterogeneity between those with and without a family history (p = .064). The OR of GC decreased with increasing duration of aspirin use, with an OR of 0.41 (95% CI, 0.18-0.95) for durations of ≥15 years. An inverse, nonsignificant association with the risk of GC was observed for the use of statins alone (OR, 0.79; 95% CI, 0.52-1.18). CONCLUSIONS: These findings suggest that aspirin use, particularly long-term use, is associated with a reduced risk of GC, whereas a similar association was not observed with statins, possibly because of the low frequency of use.

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.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Garlic consumption in relation to colorectal cancer risk and to alterations of blood bacterial DNA.

PURPOSE: Garlic consumption has been inversely associated to intestinal adenoma (IA) and colorectal cancer (CRC) risk, although evidence is not consistent. Gut microbiota has been implied in CRC pathogenesis and is also influenced by garlic consumption. We analyzed whether dietary garlic influence CRC risk and bacterial DNA in blood. METHODS: We conducted a case-control study in Italy involving 100 incident CRC cases, 100 IA and 100 healthy controls matched by center, sex and age. We used a validated food frequency questionnaire to assess dietary habits and garlic consumption. Blood bacterial DNA profile was estimated using qPCR and16S rRNA gene profiling. We derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of IA and CRC according to garlic consumption from multiple conditional logistic regression. We used Mann-Whitney and chi-square tests to evaluate taxa differences in abundance and prevalence. RESULTS: The OR of CRC for medium/high versus low/null garlic consumption was 0.27 (95% CI = 0.11-0.66). Differences in garlic consumption were found for selected blood bacterial taxa. Medium/high garlic consumption was associated to an increase of Corynebacteriales order, Nocardiaceae family and Rhodococcus genus, and to a decrease of Family XI and Finegoldia genus. CONCLUSIONS: The study adds data on the protective effect of dietary garlic on CRC risk. Moreover, it supports evidence of a translocation of bacterial material to bloodstream and corroborates the hypothesis of a diet-microbiota axis as a mechanism behind the role of garlic in CRC prevention.

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.

Allium vegetables intake and the risk of gastric cancer in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: The role of allium vegetables on gastric cancer (GC) risk remains unclear. METHODS: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. RESULTS: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. CONCLUSIONS: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

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.

Education and gastric cancer risk-An individual participant data meta-analysis in the StoP project consortium.

Low socioeconomic position (SEP) is a strong risk factor for incidence and premature mortality from several cancers. Our study aimed at quantifying the association between SEP and gastric cancer (GC) risk through an individual participant data meta-analysis within the "Stomach cancer Pooling (StoP) Project". Educational level and household income were used as proxies for the SEP. We estimated pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) across levels of education and household income by pooling study-specific ORs through random-effects meta-analytic models. The relative index of inequality (RII) was also computed. A total of 9,773 GC cases and 24,373 controls from 25 studies from Europe, Asia and America were included. The pooled OR for the highest compared to the lowest level of education was 0.60 (95% CI, 0.44-0.84), while the pooled RII was 0.45 (95% CI, 0.29-0.69). A strong inverse association was observed both for noncardia (OR 0.39, 95% CI, 0.22-0.70) and cardia GC (OR 0.47, 95% CI, 0.22-0.99). The relation was stronger among H. pylori negative subjects (RII 0.14, 95% CI, 0.04-0.48) as compared to H. pylori positive ones (RII 0.29, 95% CI, 0.10-0.84), in the absence of a significant interaction (p = 0.28). The highest household income category showed a pooled OR of 0.65 (95% CI, 0.48-0.89), while the corresponding RII was 0.40 (95% CI, 0.22-0.72). Our collaborative pooled-analysis showed a strong inverse relationship between SEP indicators and GC risk. Our data call for public health interventions to reduce GC risk among the more vulnerable groups of the population.

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.

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.

Citrus fruit intake and gastric cancer: The stomach cancer pooling (StoP) project consortium.

Diets rich in vegetables and fruit have been associated with reduced risk of gastric cancer, and there is suggestive evidence that citrus fruits have a protective role. Our study aimed at evaluating and quantifying the association between citrus fruit intake and gastric cancer risk. We conducted a one-stage pooled analysis including 6,340 cases and 14,490 controls from 15 case-control studies from the stomach cancer pooling (StoP) project consortium. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer across study-specific tertiles of citrus fruit intake (grams/week) were estimated by generalized linear mixed effect models, with logistic link function and random intercept for each study. The models were adjusted for sex, age, and the main recognized risk factors for gastric cancer. Compared to the first third of the distribution, the adjusted pooled OR (95% CI) for the highest third was 0.80 (0.73-0.87). The favourable effect of citrus fruits increased progressively until three servings/week and leveled off thereafter. The magnitude of the association was similar between cancer sub-sites and histotypes. The analysis by geographic area showed no association in studies from the Americas. Our data confirm an inverse association between citrus fruits and gastric cancer and provide precise estimates of the magnitude of the association. However, the null association found in studies from America and in some previous cohort studies prevent to draw definite conclusions on a protective effect of citrus fruit consumption.

Alcohol consumption and gastric cancer risk-A pooled analysis within the StoP project consortium.

An association between heavy alcohol drinking and gastric cancer risk has been recently reported, but the issue is still open to discussion and quantification. We investigated the role of alcohol drinking on gastric cancer risk in the "Stomach cancer Pooling (StoP) Project," a consortium of epidemiological studies. A total of 9,669 cases and 25,336 controls from 20 studies from Europe, Asia and North America were included. We estimated summary odds-ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study-specific ORs using random-effects meta-regression models. Compared with abstainers, drinkers of up to 4 drinks/day of alcohol had no increase in gastric cancer risk, while the ORs were 1.26 (95% CI, 1.08-1.48) for heavy (>4 to 6 drinks/day) and 1.48 (95% CI 1.29-1.70) for very heavy (>6 drinks/day) drinkers. The risk for drinkers of >4 drinks/day was higher in never smokers (OR 1.87, 95% CI 1.35-2.58) as compared with current smokers (OR 1.14, 95% CI 0.93-1.40). Somewhat stronger associations emerged with heavy drinking in cardia (OR 1.61, 95% CI 1.11-2.34) than in non-cardia (OR 1.28, 95% CI 1.13-1.45) gastric cancers, and in intestinal-type (OR 1.54, 95% CI 1.20-1.97) than in diffuse-type (OR 1.29, 95% CI 1.05-1.58) cancers. The association was similar in strata of H. pylori infected (OR = 1.52, 95% CI 1.16-2.00) and noninfected subjects (OR = 1.69, 95% CI 0.95-3.01). Our collaborative pooled-analysis provides definite, more precise quantitative evidence than previously available of an association between heavy alcohol drinking and gastric cancer risk.

Exposure to PFOA and PFOS and fetal growth: a critical merging of toxicological and epidemiological data.

Toxicological and epidemiological evidence on the association between perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and birth/fetal weight was assessed. An extensive search for toxicological information in rats and mice, and a systematic search for epidemiological evidence were conducted. The linear regression coefficient (LRC) of birth weight (BrthW) on PFOA/PFOS was considered, and separate random effects meta-analyses for untransformed (i.e. not mathematically transformed) and log-transformed values were performed. Toxicological evidence: PFOA: 12 studies (21 datasets) in mice showed statistically significant lower birth/fetal weights from 5 mg/kg body weight per day. PFOS: most of the 13 studies (19 datasets) showed lower birth/fetal weights following in utero exposure. Epidemiological evidence: Sixteen articles were considered. The pooled LRC for a 1 ng/mL increase in untransformed PFOA (12 studies) in maternal plasma/serum was -12.8 g (95% CI -23.2; 2.4), and -27.1 g (95% CI -50.6; -3.6) for an increase of 1 loge ng/mL PFOA (nine studies). The pooled LRC for untransformed PFOS (eight studies) was -0.92 g (95%CI -3.4; 1.6), and for an increase of 1 loge ng/mL was -46.1(95% CI -80.3; -11.9). No consistent pattern emerged for study location or timing of blood sampling. CONCLUSIONS: Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 102-103 times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.

The global gastric cancer consortium: an update from the Stomach cancer Pooling (StoP) project.

We updated to December 2023 the main findings of the stomach cancer pooling (StoP) project including about 13 000 cases and 31 000 controls from 29 case-control and 5 nested studies. The StoP project quantified more precisely than previously available the positive associations of tobacco smoking, high alcohol consumption, meat intake, selected occupations (e.g. agricultural and miners), gastric ulcer and family history with gastric cancer and the inverse associations with socioeconomic status and selected aspects of diet (fruits, including citrus fruits, vegetables, including allium and mushrooms, and polyphenols). No consistent associations were found with coffee, yoghurt and leisure-time physical activity, metformin or proton pump inhibitors use.

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

BACKGROUND: Evidence on the potential association between dietary copper intake and gastric cancer (GC) is lacking. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project-an international consortium of epidemiological studies on GC. METHODS: Data from five case-control studies within the StoP Project were included (2448 cases, 4350 controls). We estimated adjusted odds ratios (ORs) and 95% CIs for the association between dietary copper intake and GC using multivariable mixed-effects logistic regression models. We also modelled the dose-response relationship between copper intake and GC using a logistic mixed-effects model with fractional polynomial. RESULTS: The OR for the highest quartile of copper intake compared with the lowest one was 0.78 (95% CI: 0.63-0.95; P for trend = 0.013). Results were similar for non-cardia-type (OR: 0.72; 95% CI: 0.57-0.91), intestinal-type (OR: 0.75; 95% CI: 0.56-0.99) and other histological-type GC (OR: 0.65; 95% CI: 0.44-0.96). The dose-response analysis showed a steep decrease in ORs for modest intakes (<1 mg/day), which were subsequently steady for ≤3 mg/day (OR: 0.09; 95% CI: 0.02-0.41) and slowly increased for higher intakes. CONCLUSIONS: The findings of our large study suggest that copper intake might be inversely associated with GC, although their confirmation by prospective studies is required.

Yoghurt Intake and Gastric Cancer: A Pooled Analysis of 16 Studies of the StoP Consortium.

BACKGROUND: Yoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC). METHODS: We pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted. RESULTS: The analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94-1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88-0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85-0.99) and 0.78 (95% CI = 0.73-0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91-1.02) for cardia, 1.03 (95% CI = 1.00-1.07) for non-cardia, 1.12 (95% CI = 1.07-1.19) for diffuse and 1.02 (95% CI = 0.97-1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women. CONCLUSIONS: We found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association.

Flavonoid Intake in Relation to Colorectal Cancer Risk and Blood Bacterial DNA.

Flavonoids have been inversely associated to colorectal cancer (CRC) and are plausible intermediaries for the relation among gut microbiome, intestinal permeability and CRC. We analyzed the relation of flavonoid intake with CRC and blood bacterial DNA. We conducted a case-control study in Italy involving 100 incident CRC cases and 200 controls. A valid and reproducible food-frequency questionnaire was used to assess dietary habits and to estimate six flavonoid subclass intakes. We applied qPCR and 16S rRNA gene profiling to assess blood bacterial DNA. We used multiple logistic regression to derive odds ratios (ORs) of CRC and Mann-Whitney and chi--square tests to evaluate abundance and prevalence of operational taxonomic units (OTUs) according to flavonoid intakes. Inverse associations with CRC were found for anthocyanidins (OR for the highest versus the lowest tertile = 0.24, 95% confidence interval, CI = 0.11-0.52) and flavanones (OR = 0.18, 95% CI = 0.08-0.42). We found different abundance and prevalence according to anthocyanidin and flavanone intake for OTUs referring to Oligoflexales order, Diplorickettsiaceae family, Staphylococcus, Brevundimonas, Pelomonas and Escherischia-Shigella genera, and Flavobacterium and Legionella species. The study provides evidence to a protective effect of dietary anthocyanidins and flavanones on CRC and suggests an influence of flavonoids on blood bacterial DNA, possibly through intestinal permeability changes.