NEW YORK (Reuters Health) - Antibodies to Vacuolating cytotoxin A (VacA), one of the major toxins secreted by Helicobacter pylori, show a relationship with colorectal cancer, according to a large study of serum.
As Dr. Meira Epplein told Reuters Health by email, "Our study has established an association of antibodies to the H. pylori protein VacA and an increased risk of colorectal cancer (CRC), particularly for African Americans, who are more likely both to harbor H. pylori and to be diagnosed with colorectal cancer."
In an October 5 online paper in Gastroenterology, Dr. Epplein of Duke University School of Medicine, Durham, North Carolina and colleagues note that although most of the world's population harbors H. Pylori infection, only a small proportion develop gastric cancer; thus, "it is important that both bacterial virulence factors and host responses, such as the individual's immune response to H pylori infection, are considered."
As part of that effort, the team used H. pylori multiplex serologic assays to analyze serum samples from a diverse population across the U.S. This consisted of 4063 incident cases of CRC, collected before diagnosis, and 4063 matched samples from people without CRC. Antibody responses to 13 H. pylori proteins, including the virulence factor VacA were recorded.
Overall, 40% of the controls without CRC and 41% of those with CRC were seropositive for H. pylori (odds ratio 1.09). Results varied substantially by race and ethnicity, with seroprevalence being lowest in whites. This amounted to 33% for controls and 35% for cases. For Asian Americans the corresponding proportions were 39% and 46%. For African Americans, they were 65% and 71% and for Latinos, 77% and 74%.
In whites and Latinos, there was no association with the risk of CRC, but suggestions of increased odds were seen with Asian Americans (OR, 1.30) and African Americans (OR, 1.30) although this did not reach statistical significance.
However, H. pylori VacA-specific sero-positivity was associated with 11% higher odds of CRC. This association was particularly strong among African Americans (OR, 1.45). In addition, the odds of CRC increased significantly with level of VacA antibody in the overall cohort and specifically among African Americans. This was most pronounced in the those in the highest quartile of VacA antibody level.
"Whether this association is causal we cannot yet determine," continued Dr. Epplein, "but even if H. pylori is not directly causing colorectal cancer, high antibody levels of VacA could serve as a biomarker for increased colorectal cancer risk, that could then be utilized for personalized prevention through an increased schedule of colorectal cancer screenings."
Commenting by email, Dr. Ming-Shiang Wu, a Distinguished Professor at National Taiwan University, Taipei, told Reuters Health, "Whether H. pylori infection might lead to extra-gastric diseases is a controversial issue, especially in the current topic of colon cancer. Previous studies in this field are criticized for methodological problems including lack of adjustment of confounding or comorbid factors, lack of biologic plausibility and lack of dose-responsive effect. As compared to previous studies, the current one has the advantage of large nested case-control design (analysis of pre-diagnostic serum) and analysis of multiplex serology.
Dr. Wu, who has conducted wide-ranging research in the field, concluded, however, that "the findings, although intriguing, are still preliminary and do not have mechanistic data."
"Collectively," Dr. Wu said, "this study only supports that VacA may be associated with CRC risk in African Americans and can serve as a marker. The mechanisms and whether such association can be reproduced in other populations remain to be further investigated."