Approved Research

Human genome, lifestyle factors, and their interplay in relation to gastrointestinal cancer risk and survival.

Lay summary

Gastrointestinal cancers are the common cause of morbidity and mortality, and caused by a mix of genetic and non-genetic factors. The accurate genetic and lifestyle factors and their interplay for gastrointestinal cancers as well as each specific cancer need identification.

The science of genomics has already provided insight into some predisposition genes for gastrointestinal cancer risk. However, there remain many unknown genes and novel genes that can influence gastrointestinal cancer risk and survival need to be uncovered. Lifestyle factors have been reported to influence cancer progression. However, the actual contribution proportion of the genetic and lifestyle factors to the gastrointestinal cancer risk need to be quantified. The interplay between genetic and lifestyle factors are largely unknown. The combination of the genetic and lifestyle factors in precisely predicting gastrointestinal cancer risk and survival remains to be established.

Thus, we propose to leverage the newly available whole genome data in the UK Biobank to (1) discover novel genes associated with gastrointestinal cancer risks and survival, and estimate penetrance (the cancer risk associated with gene variants) of both novel and known pathogenic genes in gastrointestinal cancer; (2) identify the interactions of human genome and lifestyle factors, and reveal the extent to which the increased gastrointestinal cancer risk by genetic factor can be offset by a healthy lifestyle; (3) quantify the contribution proportions of human genome and lifestyle factors to gastrointestinal cancer risks and survival, and make prediction models for gastrointestinal cancer risks and survival by combining them.

The project duration will be 3 years. This study will provide significant insights into the association and prediction of the human genome and lifestyle factors for gastrointestinal cancer risk and survival. It can help risk stratification, tailored screening, prevention, and treatments of gastrointestinal cancer. We will thus provide comprehensive prevention and management strategies for gastrointestinal cancer.