Genetic Susceptibility And The Environment In Cancer Risk

$578,435ZIAFY2014ESNIH

National Institute Of Environmental Health Sciences

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Abstract

Summary: Global decrease in DNA methylation is a common feature of cancer and is associated with genomic and chromosomal instability in tumor tissue. We used prospectively collected samples to examine whether global DNA methylation profiles of blood samples was associated with increased risk of developing breast cancer. Using pyrosequencing of LINE-1 repetitive elements we showed 1.75 fold increased risk for women in the lowest quartile of DNA methylation. These differences were detectable months to years before the clinical diagnosis of breast cancer. In addition we show that several common polymorphisms in one-carbon metabolism genes were associated with either methylation, or directly with breast cancer risk. DNA methylation can change in response to environmental exposures, such as chemical pollutants, diet, and other lifestyle factors. This study links changes in blood DNA methylation to future risk of developing cancer and may suggest lifestyle strategies for lowering risk. Recent work in the laboratory has focused on prostate cancer aggressiveness. Few genetic risk factors have been uncovered that contribute specifically to the racial disparity in prostate cancer observed in African Americans. With the advent of Ancestry Informative Marker (AIM) single nucleotide polymorphism (SNP) panels and powerful genetic strategies such as Mapping by Admixture Linkage Disequilibrium (MALD) it is possible to discover genes that underlie ethnic variation in disease risk. Using these markers in the North Carolina-Louisiana Prostate Cancer Project we have identified areas on chromosome 8q24.21 and 11p13 associated with increased risk.

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