Helicobacter pylori Infection and Colorectal Cancer Risk
Helicobacter pylori Infection and Colorectal Cancer Risk
Evidence concerning the role of Helicobacter pylori infection in the development of colorectal cancer remains controversial. The authors assessed the association of H. pylori seroprevalence with risk of colorectal cancer in a large population-based case-control study from Germany in 2003–2007. Serum antibodies to H. pylori in general and the cytotoxin-associated gene A protein (CagA) were measured in 1,712 incident colorectal cancer cases and 1,669 controls. The association between H. pylori seroprevalence and colorectal cancer risk was estimated by logistic regression, with adjustment for potential confounders and stratification by age group, sex, anatomic subsites, and cancer stage. Overall, H. pylori seroprevalence was higher in cases (46.1%) than in controls (40.1%), resulting in an age- and sex-adjusted odds ratio of 1.30 (95% confidence interval (CI): 1.14, 1.50). Adjustment for established colorectal cancer risk factors decreased the odds ratio to 1.26 (95% CI: 1.09, 1.47), with a further reduction to 1.18 (95% CI: 1.01, 1.38) after additional adjustment for previous colorectal endoscopy. Stratified analyses showed risk elevation to be essentially confined to left-sided colorectal cancer, with an odds ratio of 1.22 (95% CI: 1.02, 1.45), suggesting that H. pylori infection may be associated with a small yet relevant risk increase in the left colorectum
Colorectal cancer is the third most common cancer and the fourth leading cause of cancer-related death globally. Its etiology is complex and remains incompletely understood, even though a number of genetic and environmental risk factors are meanwhile established. Several studies have suggested that chronic infection with the gastric bacterium Helicobacter pylori, which is an established strong risk factor for noncardia gastric cancer, may also be associated with a moderately increased risk of colorectal cancer. However, results were not consistent, and null results have also been reported. Two pertinent meta-analyses combining results of 11 studies and 13 studies yielded summary odds ratios of 1.4 (95% confidence interval (CI): 1.1, 1.8) and 1.5 (95% CI: 1.2, 1.9), respectively, suggesting a moderate yet relevant increase in colorectal cancer risk among those infected. However, evidence was limited by a number of factors, including limited sample size of studies and heterogeneous and often incomplete control of confounding. In particular, none of the previous studies controlled for former colorectal endoscopy, the strongest preventive factor known to date, and the number of cases remained below 385 in each of the single studies and below 1,710 in all studies combined, which limited the possibilities of more specific analyses according to cancer site, age, sex, or other key determinants of colorectal cancer risk. We thus aimed to assess the association between H. pylori seropositivity and the risk of colorectal cancer in a large population-based case-control study, paying particular attention to careful control for confounding, consideration of potential virulence factors of the infectious agent, and potential variation of risk with respect to age, sex, anatomic subsites, and cancer stage.
Abstract and Introduction
Abstract
Evidence concerning the role of Helicobacter pylori infection in the development of colorectal cancer remains controversial. The authors assessed the association of H. pylori seroprevalence with risk of colorectal cancer in a large population-based case-control study from Germany in 2003–2007. Serum antibodies to H. pylori in general and the cytotoxin-associated gene A protein (CagA) were measured in 1,712 incident colorectal cancer cases and 1,669 controls. The association between H. pylori seroprevalence and colorectal cancer risk was estimated by logistic regression, with adjustment for potential confounders and stratification by age group, sex, anatomic subsites, and cancer stage. Overall, H. pylori seroprevalence was higher in cases (46.1%) than in controls (40.1%), resulting in an age- and sex-adjusted odds ratio of 1.30 (95% confidence interval (CI): 1.14, 1.50). Adjustment for established colorectal cancer risk factors decreased the odds ratio to 1.26 (95% CI: 1.09, 1.47), with a further reduction to 1.18 (95% CI: 1.01, 1.38) after additional adjustment for previous colorectal endoscopy. Stratified analyses showed risk elevation to be essentially confined to left-sided colorectal cancer, with an odds ratio of 1.22 (95% CI: 1.02, 1.45), suggesting that H. pylori infection may be associated with a small yet relevant risk increase in the left colorectum
Introduction
Colorectal cancer is the third most common cancer and the fourth leading cause of cancer-related death globally. Its etiology is complex and remains incompletely understood, even though a number of genetic and environmental risk factors are meanwhile established. Several studies have suggested that chronic infection with the gastric bacterium Helicobacter pylori, which is an established strong risk factor for noncardia gastric cancer, may also be associated with a moderately increased risk of colorectal cancer. However, results were not consistent, and null results have also been reported. Two pertinent meta-analyses combining results of 11 studies and 13 studies yielded summary odds ratios of 1.4 (95% confidence interval (CI): 1.1, 1.8) and 1.5 (95% CI: 1.2, 1.9), respectively, suggesting a moderate yet relevant increase in colorectal cancer risk among those infected. However, evidence was limited by a number of factors, including limited sample size of studies and heterogeneous and often incomplete control of confounding. In particular, none of the previous studies controlled for former colorectal endoscopy, the strongest preventive factor known to date, and the number of cases remained below 385 in each of the single studies and below 1,710 in all studies combined, which limited the possibilities of more specific analyses according to cancer site, age, sex, or other key determinants of colorectal cancer risk. We thus aimed to assess the association between H. pylori seropositivity and the risk of colorectal cancer in a large population-based case-control study, paying particular attention to careful control for confounding, consideration of potential virulence factors of the infectious agent, and potential variation of risk with respect to age, sex, anatomic subsites, and cancer stage.
