NEW YORK (GenomeWeb) – The National Cancer Institute has recently awarded a five-year, $4.1 million grant to MD Anderson Cancer Center researcher Michelle Hildebrandt to conduct a large-scale sequencing study to identify rare genomic variants associated with inherited ovarian cancer susceptibility.
Through genome-wide association studies, Hildebrandt and collaborators have identified 11 loci associated with ovarian cancer risk and plan to publish an additional six in the coming months, she wrote in her grant's abstract.
"However, these variants combined only explain less than 5 percent of the heritable risk of ovarian cancer," she noted, adding that even when BRCA1 and BRCA2 mutations are taken into account, about 60 percent of familial ovarian cancer cases are unresolved.
Hypothesizing that rare variants in multiple genes are responsible for a measure of ovarian cancer susceptibility and that these variants can be used to predict disease risk, she and her team aim to perform whole-exome sequencing followed by targeted sequencing in 8,000 ovarian cancer patients, as well as 8,000 matched controls of European descent.
Given the well-established differences in prognosis between European and African American ovarian cancer patients, Hildebrandt will also sequence the top candidate genes identified in the first experiments in an ongoing study of African American women with the disease.
As part of the NCI-funded effort, she also aims to sequence ovarian tumors from individuals with rare germline susceptibility variants in order to link somatic and germline variation in mediating ovarian cancer risk.
These analyses, Hildebrandt wrote, have the potential to enhance ovarian cancer risk assessment, helping refine existing screening and prevention approaches, and develop new ones.
The grant project began on August 1 and runs until the end of July 2016.