Lisa Mirabello

National Cancer Institute, NIH

Principal Investigator

PLCO (Learn more about this study)

PLCO-267

Mar 29, 2017

Germline genetics of metastasis: an across cancer analysis

Metastasis to distant secondary sites is a strong determinant of cancer survival. It is possible that shared inherited variation in genes that accelerate or retard cellular activities critical to the complex metastatic process may impact the clinical onset of metastatic disease for solid tumors in general. Our aim is to conduct a GWAS of solid cancer cases with advanced stage (Stage 4, metastatic disease) versus those with early stage (Stage 1-2, localized disease) cancer to determine if there are SNPs associated with the risk of metastatic disease that are shared across diverse cancer types. We propose to evaluate this in cases of lung, prostate, bladder, renal, brain, breast, endometrial, ovarian, gastric, esophagus, gastrointestinal, colorectal, osteosarcoma, and pancreas cancer. The goal is to identify novel shared metastasis risk loci; we will not focus on individual cancer types as a primary outcome. We propose to specifically follow-up our novel finding that genetic variation within the NFIB gene region is associated with osteosarcoma metastasis, and plan to determine if this NFIB locus is associated with metastasis in other solid cancers. We will evaluate the solid cancer cases listed above for associations between variation within this NFIB gene region and metastatic disease. To conduct these analyses, we need specific outcome variables, including tumor stage and/or metastasis at dx.
We plan to examine GWAS data with cases of lung, prostate, bladder, renal, brain, breast, endometrial, ovarian, gastric, esophagus, gastrointestinal, colorectal, osteosarcoma, and pancreas cancer and determine if SNPs exhibit significant effects, taking into account study, cancer type, age group, smoking status, and gender.