Colorectal cancer (CRC) is a common cancer, and the third leading cause of cancer death in the United States. CRC rates are substantially higher in western Europe and North America compared to the rest of the world. In part, this is due to diet and lifestyle (e.g., red meat and processed food consumption, obesity, sedentary lifestyle). Helicobacter pylori (H. pylori) is a bacterial infection affecting > 50% of the worlds population. It causes ulcers and stomach cancer. However, H. pylori treatment with antibiotics drastically reduces stomach cancer risk. A recent study also found that a single H. pylori treatment with antibiotics in China, where stomach cancer is quite common, also reduced death from CRC. There is some evidence that H. pylori may increase CRC risk. It is therefore reasonable to examine if H. pylori treatment reduces CRC risk as it does with stomach cancer. In this study we will examine the association between H. pylori treatment with antibiotics and CRC risk.
This is a novel, low risk, high reward proposal that leverages existing population-based data sources to quickly and efficiently perform a study. It would provide preliminary evidence as to whether H. pylori treatment could reduce the burden of CRC at the population level. This is particularly important because CRC rates are increasing in younger populations despite a decline among older persons. Because CRC incidence is so high in western countries, even a 10% reduction in CRC incidence attributable to H. pylori treatment would present an important intervention opportunity.
CRC incidence is substantially higher in western Europe and North America compared to the rest of the world. In part, this is because many of the moderate risk factors associated with CRC (e.g., red meat consumption, processed foods, obesity, smoking, alcohol consumption and sedentary lifestyle) are more prevalent in the west.1
Helicobacter pylori (H. pylori) is responsible for almost 90% of non-cardia gastric cancers.2,3. A review of H. pylori and CRC incidence provided supportive evidence and plausible biological mechanisms by which H. pylori infections may also increase risk of CRC incidence or CRC precursor lesions.4 The evidence is limited, especially in western Europe and North America. If H. pylori infections increase the risk of CRC or its precursors, it is reasonable to ask if treating H. pylori infections could substantially reduce the burden of CRC in the west as H. pylori treatment has reduced gastric cancer incidence in the east. This question has not however been addressed.
In this study, we will examine the association between H. pylori eradication treatment and CRC risk using a case-control study supplemented with serology information from the UK Biobank using novel statistical methods. Unlike the UK Biobank, the CPRD does not contain serologically confirmed H. pylori status. We will use information obtained from our UK Biobank study where HP status is measured on a subset of participants (N~10,000) to estimate the probability that a person is H. pylori+ given that s/he was not treated. This information can then be combined with the CPRD data to estimate the treatment effect on CRC risk among individuals predicted to be H. pylori+ using an estimating equations approach or a mixture model. We will test our novel approach with a positive control outcome (gastric cancer) and negative control outcomes (cancer of the prostate and female breast).
1. Colorectal cancer (CRC) incidence
2. Gastric cancer incidence
3. Prostate cancer
4. Female Breast cancer
Monica DArcy - Chief Investigator - National Cancer Institute ( NCI )
Monica DArcy - Corresponding Applicant - National Cancer Institute ( NCI )
Maria Constanza Camargo - Collaborator - National Cancer Institute ( NCI )
Mitchell Gail - Collaborator - National Cancer Institute ( NCI )
Ruth Pfeiffer - Collaborator - National Cancer Institute ( NCI )
HES Admitted Patient Care;HES Outpatient;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation