Researchers Climb the Family Tree: Understanding Inherited Risk for Colorectal Cancer

Grandpa's colorectal cancer may play more of a role in your risk than anyone realized. What's more, the findings of Huntsman Cancer Institute (HCI) researchers published in the March 2010 issue of Gastroenterology also influence colorectal screening guidelines on a national level.

Family history is a well-known factor when determining a person's risk for colorectal cancer. But most research in the field has looked only at how immediate family members (parents, siblings, and children) are involved. HCI investigators went further to understand this factor—and defined new risk categories to estimate a person's chances of developing colorectal cancer based on first-, second-, and third-degree family members.

burt and cannon-albright colon cancer risk

Randall Burt, MD and Lisa Cannon-Albright, PhD

"We wanted to estimate an individual's risk for colorectal cancer based on the presence of colorectal cancer in close and distant relatives," says Lisa Cannon-Albright, PhD, Division Chief and Professor in the Division of Genetic Epidemiology at the University of Utah School of Medicine. Cannon-Albright conceived of the study's idea and served as academic advisor to then PhD candidate and co-author David Taylor, PhD.

"We found that you need to know more than 'yes' or 'no' as an answer to the question 'Do you have any relatives with colorectal cancer?' to give a good risk estimate for someone," says Cannon-Albright. "A higher number of first-degree relatives with colorectal cancer means you have a higher risk; if you have close and distant relatives with the disease, then your risk is greater still."

pedigree colon cancer

Family Pedigree Chart
Proband: person being studied
First-degree relatives (FDR): parent, sibling, child
Second-degree relatives (SDR): grandparents, grandchildren, aunts and uncles
Third-degree relatives (TDR): cousins, great-grandparents, great-grandchildren


What sets this study apart is how HCI investigators accessed so many family histories.

"We took advantage of a unique Utah resource," says Randall Burt, MD, Senior Director of Prevention and Outreach and a gastroenterologist at HCI.

That is the Utah Population Database (UPDB), a computerized resource housed at HCI that is linked to a statewide cancer registry. The UPDB contains extensive medical and demographic information for approximately 7 million people. This study analyzed all genealogies comprising at least three generations, totaling more than 2.3 million people.

"The Utah Population Database was absolutely essential for this study," says Cannon-Albright. "There really is no other resource in the world from which you can perform this sort of risk estimation."

A follow-up study published in 2011 in Genetics in Medicine showed patients with a known inherited risk of colorectal cancer are more compliant than the general population with colonoscopy guidelines; however, their compliance did not correspond with the degree of risk.

This 2011 study followed participants aged 30-90 years who not only had a family history in the UPDB, but had also been seen during a five-year period at Intermountain Healthcare, the largest health care system in the Intermountain West, with which HCI has an established research collaboration.

"The good news is we know those with a high familial risk got a colonoscopy," says Burt. "Now we want to further study screening compliance of those in the highest-risk categories (people with first-, second-, and third-degree relatives diagnosed with colorectal cancer)."

Although several options exist to screen for colorectal cancer, Burt describes colonoscopy as the standard for those with a family risk. "Because we have this further understanding of familial colorectal cancer risk, these findings will influence national screening guidelines and ultimately help health care providers know under which risk category a patient falls. This determines the patient's recommended age to begin regular colonoscopies and how often."

Cannon-Albright sees both the health and financial benefit to patients. "At no cost at all to patients, we can look at the family history involvement of colorectal cancer to determine their risk of the disease, and then give them personalized screening recommendations. HCI not only helps with the research, but can integrate these risk estimates into clinical care."

HCI's Family Cancer Assessment Clinic (FCAC) is one example.

"This study provides us with specific data that we can use to provide risk estimates to patients with a variety of different colorectal cancer patterns," says Wendy Kohlmann, MS, CGC, Director of the Genetic Counseling Shared Resource and a board-certified genetic counselor in the FCAC.

Genetic counselors are health care professionals with specific training to evaluate an individual's personal and family history for features or patterns that may suggest an inherited risk for disease. They can provide personalized cancer risk assessment, information about whether genetic testing may be helpful, and cancer screening recommendations. Watch the video below about genetic counseling at HCI.

HCI's continued studies and clinical trials related to familial cancer risk—and personalized screening recommendations based on those findings—translate into better outcomes for patients. "What gives us hope is that through emphasizing what works, we can reduce overall morbidity and mortality of colorectal cancer, particularly among those with a familial predisposition to the disease," says Burt.