Exploring the interactions between Helicobacter pylori (Hp) infection and other risk factors of gastric cancer: A pooled analysis in the Stomach cancer Pooling (StoP) Project

Helicobacter pylori (Hp) is crucial in gastric carcinogenesis, but infection alone is not a sufficient cause, and the interaction between Hp infection and other risk factors has not been adequately studied. We conducted a pooled analysis of seven case-control studies from the Stomach cancer Pooling (StoP) Project, comprising 1377 cases and 2470 controls, to explore the interaction among Hp infection and tobacco smoking, alcohol drinking, socioeconomic status (SES) and dietary salt intake on the risk of gastric cancer. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by multivariate unconditional logistic regression. The analysis showed no consistent interaction between Hp infection and cigarette smoking, while interaction was more than multiplicative for alcohol drinking (OR = 1.38, 95% CI: 1.07-1.77, P-interaction 0.02) and high intake of salt (OR = 2.62, 95% CI: 1.88-3.65, P-interaction = 0.04). The interaction with SES followed the multiplicative model (P = 0.49), resulting in a weakening among infected individuals of the protective effect of high SES among observed Hp-negative individuals. The interactions found were more pronounced in subjects with history of peptic ulcer. The interactions with Hp infection were stronger for cigarette smoking and dietary salt in the case of noncardia cancer, and for alcohol and SES in the case of cardia cancer. No differences were found when stratifying for histologic type. This large-scale study aimed to quantify the interaction between Hp infection and other modifiable risk factors of gastric cancer revealed that the benefit of combined Hp eradication and lifestyle modification on gastric cancer prevention may be larger than commonly appreciated.This study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Project no. 21378 (Investigator Grant), and by the Italian League for the Fight Against Cancer (LILT). The authors thank the European Cancer Prevention (ECP) Organization for providing support for the StoP meetings

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.S. Morais, B. Peleteiro, N. Araújo, and N. Lunet received national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020). S. Morais received funding under the scope of the project “NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; ref. PTDC/SAU-EPI/32358/2017) funded by FEDER through the Operational Program Competitiveness and Internationalization, and national funding from FCT, and the EPIunit – Junior Research – Prog Financing (UIDP/04750/2020). N. Araújo received an individual grant (SFRH/BD/119390/2016) funded by FCT and the ‘Programa Operacional Capital Humano’ (POCH/FSE). C. La Vecchia received funding from the Italian Association for Cancer Research (AIRC, investigator grant no. 21378). All authors received support from the European Cancer Prevention (ECP) Organization for project meetings. All authors thank all MCC-Spain study collaborators (CIBERESP, ISCIII, ISGlobal, ICO, University of Huelva, University of Oviedo, University of Cantabria, University of León, ibs. Granada, Instituto Salud Pública de Navarra, FISABIO, Murcia Regional Health Authority and cols). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact

Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of Case‐Control Studies of the Stop Consortium

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case‐control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83–0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77–0.94) and non‐cardia GC (OR = 0.87, 95% CI = 0.81–0.94), and for diffuse (OR = 0.79, 95% CI = 0.69–0.89) and intestinal type (OR = 0.88, 95% CI = 0.79–0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.This study was supported by the Fondazione AIRC per la Ricerca sul Cancro, Project no. 21378 (Investigator Grant). The Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020) and the Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR; LA/P/0064/2020) were funded by the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education). SM was supported by the project “NEON‐PC—Neuro‐oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI‐01‐0145‐FEDER‐032358; ref. PTDC/SAU‐EPI/32358/2017), which is funded by FEDER through the Operational Programme competitiveness and Internationalization, and national funding from FCT and the EPIUnit—Junior Research—Prog Financing (UIDP/04750/2020). The authors thank the European Cancer Prevention (ECP) Organization for providing support for the StoP Project meetings and all MCC‐Spain study collaborators (CIBERESP, ISCIII, ISGlobal, ICO, University of Huelva, University of Oviedo, University of Cantabria, ibs.Granada, Instituto Salud Pública de Navarra, FISABIO, Murcia Regional Health Authority and cols)

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\u2013control 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\u20130.87). 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. \ua9 2018 UIC

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.Associazione Italiana per la Ricerca sul Cancro, Grant/Award Numbers: 21378, European Cancer Prevention Organization; European Regional Development Fund (COMPETE 2020), European Social Fund (POCH), Foundation for Science and Tecnology, and Ministry of Science, Technology and Higher Education, Grant/Award Numbers: PD/BD/105823/2014, UIDB/04750/2020, POCI-01-0145-FEDER-032358, PTDC/SAU-EPI/32358, SFRH/BD/102181/2014, SFRH/BPD/108751/2015; Italian League for Fight Against Cancer; Italian Ministry of Health, Grant/Award Number: GR-2011-0234794

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.Our study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Project no. 21378 (Investigator Grant), by the Italian Ministry of Health (Young Researchers, GR-2011-02347943 to SB), by the Italian League for the Fight Against Cancer (LILT) and by the Associazione Industriale delle Carni e dei Salumi (ASSICA, to the Department of Clinical Sciences and Community Health, University of Milan). Our study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). AF (PD/BD/105823/2014) was awarded with an individual scholarship through national funding from FCT/MCTES. Individual grants attributed to ARC (SFRH/BD/102181/2014), and BP (SFRH/BPD/108751/2015) were funded by the FCT and the “Programa Operacional Capital Humano” (POCH/SE). SM was funded under the project “NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline “ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). Valentina Rosato was supported by a fellowship by the Italian Foundation for Cancer Research (FIRC #18104)