Approved Research

Exploring genetic and environmental factors contributing to cancer etiology, risk, and prognosis and difference between solid and hematological cancers

Lay summary

The link between environmental factors, genetics and the development of cancer continues to be an important focus in research.  Environmental factors play an important role in the biological differences of different types of cancers. Genetic epidemiology studies demonstrate the importance of genetic risk passed on in families and gene-environment interactions in risk of cancer and related outcomes.  However, we still have left to identify environmental vs genetic risk factors that increase a person's risk of getting cancer.  It is important to explore these relationships and consider possible interplay between environment and genetics. Based on this rationale we plan to leverage the UK Biobank to explore blood and solid cancer subtypes, differences, and association between modifiable risk factors (like diet and BMI), genetics, and their interactions. A more complete comprehension of the genetic and environmental factors that affect the probability of getting a cancer, or of surviving after a cancer diagnosis, is important for novel and more effective approaches to cancer prevention, diagnosis and treatment.  We aim to explore the relationships and associations between modifiable risk factors, related biomarkers (inflammatory), and genetic risk and compare differences between solid and blood cancers. We will explore environmental factors, genetic variants, and interactions, creating scores for risk stratification and outcome prediction. Our specific aims are as follows: 

AIM 1: To evaluate modifiable environmental (E) and clinical risk factors association with higher risk and prognosis of certain cancers and the difference between solid and blood cancers.

AIM 2:  To explore genetic susceptibility (G) associations with cancer and differences between solid and blood cancers.

AIM 3: To test gene-environment (GxE) interactions associated with cancer risk and prognosis and difference between solid and blood cancers.

Epidemiology paired with genetic epidemiological methods are valuable tools for prevention efforts at population and clinical levels, aiding in risk/prognostic stratification and identifying functional pathways for therapeutic advances. Overall this research may contribute population-level risk factor guidelines for prevention efforts in the public health arena. We estimate the project duration will take approximately 3 years, running concurrently with on-going R01/U01s. We will re-apply to UKBB when needed.

Our main research question is whether genetic and environmental factors (such as clinical and modifiable lifestyle factors) are associated with increased risk and prognostic outcomes of cancer (specifically; hematological cancers, breast cancer, and gastrointestinal cancers, including esophageal, stomach, colorectal, pancreatic, and liver cancer including its precursors, such as non-alcoholic fatty liver disease and liver cirrhosis). We aim to explore the relationships and associations between modifiable risk factors, related biomarkers (e.g., inflammatory), and genetic susceptibility and compare differences between solid and hematological cancers. We will explore environmental factors, genetic variants, and interactions, creating scores for risk stratification and outcome prediction. Further we will evaluate and validate using in-silico pathways and biomarkers contributing to cancer etiology.  We plan to explore these differences of identified associations between solid tumors and hematological malignancies.

Our specific aims are as follows:

AIM 1: To evaluate modifiable environmental (E) and clinical risk factors association with higher risk and prognosis of certain cancers and the difference between solid and hematological cancers.

AIM 2:  To explore genetic susceptibility (G) (common/rare variants, pleiotropy, polygenic risk scores (PRS), mendelian randomization) associations with cancer and differences between solid and hematological cancers.

AIM 3: To test gene-environment (GxE) interactions associated with cancer risk and prognosis and difference between solid and hematological cancers.

AIM 4: To evaluate the associations between environmental factors and liver cancers and its precursors, such as non-alcoholic fatty liver disease (ICD10: K75.8, K76.0) and liver cirrhosis (K74.0-K74.6).