Helicobacter pylori Antibody Reactivities and Colorectal Cancer Risk in a Case-control Study in Spain

Background: Several studies have suggested that Helicobacter pylori (H. pylori) infection is a risk factor for colorectal cancer (CRC), while others have not confirmed this hypothesis. This work aimed to assess the relation of CRC with H. pylori seropositivity and with seropositivity to 16 H. pylori proteins, in the MultiCase-Control study, MCC-Spain. Methods: MCC-Spain is a multicase-control study carried out in Spain from 2008 to 2013. In total, 2,140 histologically-confirmed incident CRC cases and 4,098 population-based controls were recruited. Controls were frequency-matched by sex, age, and province. Epidemiological data were collected through a questionnaire fulfilled by face-to-face interviews and a self-administered food-frequency questionnaire. Seroreactivities against 16 H. pylori proteins were determined in 1,488 cases and 2,495 controls using H. pylori multiplex serology. H. pylori seropositivity was defined as positivity to >= 4 proteins. Multivariable logistic regression mixed models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: H. pylori seropositivity was not associated with increased CRC risk (OR = 0.91; 95% CI: 0.71-1.16). Among H. pylori seropositive subjects, seropositivity to Cag delta showed a lower CRC risk, and risk decreased with increasing number of proteins seropositive. Seropositivity to the most recognized virulence factors, CagA and VacA, was not associated with a higher CRC risk. No statistically significant heterogeneity was identified among tumor sites, although inverse relations were stronger for left colon cancer. An interaction with age and sex was found: H. pylori seropositivity was associated with a lower CRC risk in men younger than 65 and with a higher risk in older women. Conclusions: Our results suggest that neither H. pylori seropositivity, nor seropositivity to the virulence factor CagA are associated with a higher CRC risk. A possible effect modification by age and sex was identified.The study was supported by the "Accion Transversal del Cancer," approved on the Spanish Ministry Council on the 11th October 2007, by the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), by the Instituto de Salud Carlos III grants, co-funded by FEDER funds-a way to build Europe-(grants PI08/1770, PI09/0773, PI09/1286, PI09/1903, PI09/2078, PI09/1662, PI11/01403, PI14/00613, PI14/01219, and PI15/00069), by the Fundacion Marques de Valdecilla (grant API 10/09), by Catalan Government DURSI (grants 2014SGR647 and 2014SGR756), by the Junta de Castilla y Leon (grant LE22A10-2), by the Consejeria de Salud of the Junta de Andalucia (grant 2009-S0143), by the Regional Government of the Basque Country, and by the Conselleria de Sanitat of the Generalitat Valenciana (grant AP061/10). The funders had no role in the study design, data analysis, data interpretation or writing the manuscript