Study
PLCO
(Learn more about this study)
Project ID
2008-0046
Initial CDAS Request Approval
Jan 29, 2009
Title
Can risk associated with newly identified prostate cancer susceptibility SNPs be modified?
Summary
The Cancer Genetic Markers of Susceptibility (CGEMS) group and others have recently identified at least 16 single nucleotide polymorphisms (SNPs) throughout the genome that are consistently associated with prostate cancer (Nat Genet 2008, 40:310-5). Other investigators combined SNPs and reported that men with multiple risk alleles had a higher prostate cancer risk (N Engl J Med 2008;358:910-9), including in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (Prostate 2008;68:1257-62), a component of CGEMS. Twin studies indicate that heritable factors account for 42% of prostate cancer risk, suggesting a substantial role for not only genetic, but environmental factors (N Engl J Med 2000;343:78-85). Indeed, lifestyle factors have been reported to be associated with prostate cancer. Commercial clinical tests for combinations of susceptibility alleles to predict prostate cancer risk are under development. We anticipate that patients with positive tests will ask their doctors whether they could modify lifestyle factors to reduce their risk. Thus, our proposed research question is whether men considered to be at high-risk for prostate cancer - as defined by the CGEMS genetic susceptibility profile - could attenuate their prostate cancer risk by changing lifestyle factors individually or in combination. We propose to use existing genotype data for these SNPs and questionnaire data to investigate this question in the PLCO. We will conduct a nested case (n=1,172)-control (n=1,157) analysis in which we will estimate the association between the genetic risk profile and prostate cancer within strata of modifiable factors. We will test whether the association is attenuated in men who are exposed to modifiable factors hypothesized to be beneficial. If we identify such factors, our work may set the stage for randomized prevention trials in men at high genetic risk for this cancer.
Aims
To test whether the association between the CGEMS genetic risk profile and prostate cancer overall and by aggressiveness differs between strata of modifiable factors, including those predictive of good health and those purported to be inversely associated with risk of prostate cancer. We hypothesize that prostate cancer risk associated with a high-risk genetic profile is reduced in men who limit alcohol, do not smoke, are normal weight, are active, have higher fruit and vegetable intake, lower animal product intake, use statins and non-steroidal anti-inflammatory drugs, for example.
Collaborators
Elizabeth Platz (Johns Hopkins (Epidemiolgy))
Richard Hayes (DCEG)
Wen-Yi Huang (DCEG)
Stacey Loeb (Johns Hopkins (Urology))
William Issacs (Johns Hopkins (Urology))
