Approved research

Causal relationships between environmental exposures and risk of human cancers: a phenome-wide mendelian randomization analysis

Lay summary

Cancer is a leading cause of human death worldwide. Environmental factors play a major role in the development of most types of human cancers. Over the past century, epidemiological studies particularly large prospective cohort studies have linked many environmental factors with risk of human cancers. Observational studies can identify epidemiological associations between environmental exposures and risk of diseases such as cancer. However, whether these exposures directly cause cancer or are simply a risk factor of cancer are largely unclear perhaps due to potential confounders or reverse causality. Thus far, only a few environmental factors have been found to be causally associated with risk of specific cancers, for example, cigarette smoking and risk of lung cancer. Because a lot of environmental factors are modifiable, prevention or early intervention of them may eventually reduce cancer incidence if the associations between these factors and cancer are causal. In this project, we aim to systematically evaluate the potential causal relationships between well-established environmental factors and human cancers. To address this issue, will carry out a prospective cohort study, a phenome-wide association study, and a mendelian randomization analysis using data from the UK Biobank, our group, other public available datasets and published studies. The potential causal effect of a specific exposure (risk factor) on the risk of over cancer or an individual cancer (outcome) is estimated as the ratio of the coefficient of the association between genetics and outcome to that of the association between genetics and the risk factor. We also investigate associations of cancer susceptibility variants with environmental exposures to test for potential reverse causality. We will start analyses as soon as data are available and plan to finish this project and send manuscripts to authors for review within 36 months after we receive the data. We hope that this study will provide a profile of causal relationships between environmental exposures and cancer risk and may help identify novel biological pathways and therapeutic targets for improving prevention and treatment of cancer.