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 Cagdelta 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