Project 2

Project Summary Survival for breast, prostate and colorectal cancer has improved dramatically over the past three decades as a result of advances in treatment and screening for the detection of these common cancers at an earlier stage. However, African Americans (AAs) still suffer from a higher mortality

rate after diagnosis of these cancers compared with other racial and ethnic groups. One of the consequences of prolonged survival is the possibility of developing one or more new primary cancers in their lifetime. It has been estimated that overall nearly 10% of cancer survivors will be diagnosed with a second primary cancer, with some variability in estimates across studies which

is not thoroughly understood, particularly among AAs, who we’ve been shown to have poorer survival after a second primary diagnosis. Understanding the underlying causes of second primary cancers is critical in order to design strategies for risk mitigation and early detection. Importantly, the multiple primary cancer (MPC) phenotype can be a used to understand both

genetic susceptibility and environmental risk determinants. The proposed investigation will build upon the Detroit Research on Cancer Survivors (ROCS) study, one of the largest cohorts conducted exclusively among AA cancer survivors to understand the multiplex causes of poorer outcomes in the population. We will focus both on breast, prostate

and colorectal cancer survivors enrolled in Detroit ROCS who developed a second primary cancer and use the existing infrastructure to enroll new participants diagnosed with MPCs. We will 1). sequence DNA collected from whole blood or saliva of 1000 participants diagnosed with MPCs (500 AA and 500 non-Hispanic white (NHW)) as well as 500 AA survivors diagnosed with a single

primary cancer (SPC) to characterize the mutational landscape overall and compare the spectrum and prevalence of pathogenic and likely pathogenic mutations by race and MPC/SPC status. We will 2). calculate cancer site-specific polygenic risk scores (PRS) using largely existing genotype data to understand the contribution of more common variants and PRS to the risk of MPCs.

Finally, we will 3). evaluate select environmental risk factors collected as part of the Detroit ROCS survey for their association with MPC using a 3:1 matched design comparing these participants to those diagnosed with first and only primary breast, prostate and colorectal cancer (1500 SPCs). This study is the first of its kind to address the contributing factors in the development of MPCs

among AA cancer survivors.