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

Several studies have suggested that () 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 seropositivity and with seropositivity to 16 proteins, in the MultiCase-Control study, MCC-Spain. 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 proteins were determined in 1,488 cases and 2,495 controls using multiplex serology. 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). seropositivity was not associated with increased CRC risk (OR = 0.91; 95% CI: 0.71-1.16). Among seropositive subjects, seropositivity to Cagδ 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: seropositivity was associated with a lower CRC risk in men younger than 65 and with a higher risk in older women. Our results suggest that neither 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.