Exploring the Association Between Environmental and Genetic Factors with All-Cause Mortality Using the PLCO Database
The PLCO cohort is particularly well-suited for this investigation due to its large sample size, long follow-up period, and the comprehensive data available on both cancer and non-cancer outcomes. This rich dataset will allow for a thorough analysis of how modifiable risk factors, such as lifestyle and environment, interact with genetic predispositions to influence not only cancer-specific mortality but also mortality from other chronic diseases and comorbid conditions.
By examining all-cause mortality, this study will provide a broad and integrated understanding of health risk factors and may identify new opportunities for early intervention, prevention strategies, and public health policies. Findings from this research will have implications for personalized medicine, allowing for better stratification of individuals based on their environmental and genetic risk factors and offering insights into how lifestyle modifications can reduce overall mortality risk.
Aim 1: Assess the relationship between environmental factors (e.g., smoking, diet, physical activity, air pollution) and all-cause mortality.
Using data on lifestyle and environmental exposures from the PLCO cohort, we will conduct statistical analyses to identify which environmental factors are most strongly associated with increased or reduced risk of death from any cause.
Aim 2: Investigate the influence of genetic factors on all-cause mortality.
We will analyze the genetic data available in the PLCO cohort to explore associations between genetic variants and overall mortality risk, identifying potential genetic markers of longevity or increased susceptibility to death from various causes.
Aim 3: Explore the interaction between genetic and environmental factors in determining all-cause mortality.
This aim focuses on the gene-environment interactions that may influence mortality risk. By examining the combined effects of genetic predispositions and environmental exposures, we will gain insight into how these factors work together to impact health outcomes.
Aim 4: Examine how comorbidities and chronic diseases mediate the relationship between environmental and genetic factors and all-cause mortality.
We will investigate whether the presence of comorbidities (e.g., cardiovascular disease, diabetes) modifies the associations between genetic/environmental risk factors and mortality. This will help to understand how chronic diseases contribute to the overall risk of death.
Aim 5: Identify potential preventive measures that could reduce all-cause mortality based on the identified risk factors.
Based on the findings from the above analyses, we will propose actionable public health strategies aimed at reducing all-cause mortality through lifestyle modifications, environmental policy changes, and genetic risk screening.
Shenzhen University Medical School, China-Dongsheng Hu
Shenzhen University Medical School, China-Ming Zhang
National Clinical Research Center for Cancer, National Cancer Center, Cancer Hospital, Chinese Academy of MedicalSciences and Peking Union Medical College, Beijing, China-Chunging Lin