Yan Ding

City of Hope

Assistant Research Professor

PLCO (Learn more about this study)

PLCO-27

Apr 17, 2013

Genetic Risk of Mortality in Pancreatic Cancer

We recently detected association between SNPs in Fragile Histidine Triad Gene (FHIT) and mortality due to cancers of digestive system (Exact Odds Ratio = 10.59, p = 0.010) on a prospective prostate cancer cohort of European ancestry nested in the PLCO trial. FHIT encodes a triphosphatase known to promote apoptosis responding to DNA damage in epithelia cells. Absence or down regulation of FHIT protein has been associated with clinical features of many cancers, such as presence of extraprostatic extension and high Gleason score in prostate cancer, advanced diseases in breast cancer, and shorter survival after platinum-based treatment for non-small cell lung cancer. SNPs in intron 5 of FHIT have been reported association with prostate cancer risk. We performed survival analyses under Cox proportional hazard models for the FHIT locus using imputed SNPs on a prospective prostate cancer cohort of European ancestry nested in the PLCO trial. This cohort of 2276 study subjects had 1248 affected with prostate cancer (cases) and 1028 not affected with prostate cancer (controls) by the censor time. We detected association between the SNPs and prostate cancer-specific mortality under Cox proportional models (p = 0.039) and all cause mortality (p = 0.0011) comparing patients who carry at least one risk allele to non-carriers after adjusting for age, PSA, stage, and Gleason score at diagnosis as well as treatment categories. Therefore, we propose to evaluate the association between mortality in pancreatic cancer patients and the FHIT SNPs using existing genome wide association study data on the pancreatic cancer cohort nested in the PLCO trial.