Cause-specific Mortality in PLCO Breast Cancer Patients
Principal Investigator
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-52
Initial CDAS Request Approval
Jan 6, 2014
Title
Cause-specific Mortality in PLCO Breast Cancer Patients
Summary
We recently detected association between SNPs in Fragile Histidine Triad Gene (FHIT) and mortality due to invasive breast cancer in the Women's Health Initiative (WHI). 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 breast cancer cohort nested in the WHI study. This cohort has 682 breast cancer cases who were diagnosed with invasive breast cancer before 80 years of age. We detected association between the SNPs and mortality due to breast cancer under Cox proportional models (p = 0.020) and all cause mortality (p = 0.055) comparing patients who carry at least one risk allele to non-carriers after adjusting for age at diagnosis. Therefore, we propose to evaluate the association between mortality in breast cancer cancer patients and the FHIT SNPs using existing genome wide association study data on the breast cancer cohort nested in the PLCO trial.
Aims
The Specific Aims are 1. to describe cause-specific mortality in female participants, especially those who had breast cancer, of the PLCO trial; 2. to confirm association between FHIT SNPs and mortality due to breast cancer and all causes.