Dr. Polly Newcomb, head of the Cancer Prevention Program in Fred Hutch’s Public Health Sciences Division, has just been awarded over $4 million from the National Institutes of Health to investigate a newly recognized, biologically distinct subtype of colorectal cancer known as serrated colorectal cancer.
“About 20 to 30 percent of all colorectal cancers have this subtype,” said Newcomb, a longtime public health researcher. “It’s more difficult to find and there’s evidence that these are particularly aggressive cancers. Patients are more likely to have a poorer outcome.”
Much like breast cancer and its various subtypes, colorectal cancer is biologically heterogeneous. Newcomb said serrated colorectal cancer was “a high-risk type, such as triple-negative breast cancer.”
And it hasn’t been studied much.
“There hasn’t been a lot of work done on this,” said Newcomb. “This project will definitely be one of the largest studies of serrated colorectal cancers.”
Serrated colorectal cancers — named for the serrated or saw-tooth appearance of its tumor cells — are characterized by an accumulation of aberrant methylation (abnormal modifications to the DNA) as well as specific BRAF or KRAS mutations. Her study aims to characterize the factors relating to the genetic predisposition, clinical presentation and prognosis of serrated colorectal cancer.
Newcomb will be working with Fred Hutch epidemiologist Dr. Amanda Phipps, biostatistician Dr. Chad He , gastroenterologist Dr. William Grady, and former faculty member Dr. Andrea Burnett-Hartman (now with Kaiser Permanente-Denver) on the five-year study. The study will collect new data to combine with those collected for Newcomb’s studies initiated in 1998. The cohort will include approximately 2,200 colorectal cancer cases and 1,500 cancer-free controls along with approximately 1,300 new colorectal cancer cases.
“We’ve continued to recruit and to follow up cases since 1998 and now we’re adding new cases only in Seattle,” said Newcomb. ”We’ll end up having 3,500 cases of colon cancer that we’re breaking into the subtypes.”
The project’s aims are the following: to test the differences in the distribution of genetic variants in serrated colorectal cancers as compared with other forms of colorectal cancer (and with noncancerous colon tissue); to determine the differences between serrated and non-serrated colorectal cases with respect to screening history and clinical factors at diagnosis such as tumor stage, grade, histology and anatomic site; and to evaluate differences in survival after diagnosis for individuals with serrated versus other types of colorectal cancers.
“We already know that these cancers have poorer survival, but if we can understand more about the epidemiology, we may have a better sense of how to improve the outcomes,” she said. “Our study may ultimately inform the development of novel, targeted treatment agents and cancer prevention strategies.”
Fred Hutch’s Core Center for Excellence in Hematology, led by Dr. Beverly Torok-Storb, has been replaced with a Core Center for Stem Cell and Transplantation Biology. The new core center — a five-year, $5 million cooperative agreement with NIH’s National Institute of Diabetes and Digestive and Kidney Diseases — will provide researchers at nonprofit scientific institutions across the country with access to core resources and promote collaboration among scientists to advance research.
The previous Center of Excellence has been funded for 16 years by NIDDK through a different grant mechanism (P30), through which it provided resources primarily to investigators at Fred Hutch and University of Washington. But the core had many outside users, Torok-Storb said, and grew a national reputation.
“We’ve been doing this under the P30 and we’ve been doing it so well, and our resources are so valued, that NIDDK wants to put it into the cooperative program,” Torok-Storb said. “Our faculty who provide these services enjoy national reputations and are experts in their respective fields.”
The new funding will enable the core center to establish a publicly searchable data archive that provides attribution for contributors and links investigators to annotated hematology research data.
Torok-Storb will lead the new cooperative core center. Leaders of individual cores will be Drs. Shelly Heimfeld, Hans-Peter Kiem, Michael Harkey, Patrick Paddison and Maura Parker of Fred Hutch and Dr. Larsson Omberg of Sage Bionetworks.
Grant number: U54 DK106829