This K99/R00 Career Development Award will provide the applicant, Dr. Warren Andersen, with the research
experience and training to propel her into a career as an independent investigator in the field of genetic and
molecular epidemiology with a focus on the interplay between race, modifiable risk factors, and the genetic
determinants of cancer risk and outcomes. The research plan uses Mendelian randomization methods to
evaluate the hypothesis that circulating and bioavailable vitamin D levels are associated with decreased
colorectal cancer risk. Mendelian randomization (MR) methods can be used to evaluate the associations
between long-term exposures and diseases by using genetic variants as instrumental variables in place of
exposures. Dr. Warren Andersen will also assess whether vitamin D binding protein modifies the association
between vitamin D and colorectal cancer risk. The project will leverage resources from three established
epidemiologic consortia (the ColoRectal Transdisciplinary Study (CORECT) consortium, a colorectal cancer
genome-wide association study consortium among African Americans, and the Asia Colorectal Cancer
Consortium) and the Southern Community Cohort Study to evaluate associations in large samples including
individuals of European, Asian and African descent. Dr. Warren Andersen will create race-specific genetic
scores to represent circulating vitamin D and vitamin D binding protein. Fine-mapping will be conducted to
identify potentially causal variants to be included in the vitamin D genetic scores. These genetic scores will
then be assessed for associations with overall colorectal cancer risk, and colorectal cancer risk stratified by
specific characteristics of the tumor such as COX-2 expression, PIK3CA mutation status, and stage. During the
Career Development Award Dr. Warren Andersen will gain additional skills in genetic analysis and increase her
knowledge in colorectal cancer biology and health disparities. The findings from this research project will be
used to develop and submit two R01 level projects before the completion of the Career Development Award.
The additional experience gained from this Career Development Award will prepare Dr. Warren Andersen to be
a leader in the field of genetic and molecular epidemiology of cancer, with expertise in colorectal cancer
etiology, genetic and cancer epidemiology, and the root causes of racial differences in disease risk. This
research topic is of much significance, as the Institute of Medicine's 2010 Report stated, investigation into the
causal relationships between vitamin D and total and site-specific cancers is an important research need. The
use of MR and molecular epidemiologic methods should provide a more definitive answer to the questions of
the relationships of colorectal cancer risk with circulating vitamin D, bioavailable vitamin D and vitamin D
binding protein. This study will provide insight into colorectal cancer etiology and potentially identify subgroups
of individuals who may benefit the most from vitamin D supplementation.
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