Posted by Kate Murphy on January 4th, 2008
Thousands of Americans may carry a single genetic change that puts them at high risk to develop colon cancer. Using genealogy information from two families, one in Utah and one in upstate New York with the identical genetic change, researchers traced both families back to a husband and wife who sailed to America from England in the early seventeenth century.
The mutation causes attentuated familial adenomatous polyposis (AFAP) and is responsible for a risk of increased numbers of colon polyps (adenomas) and eventually colon or rectal cancer. The research team estimates that lifetime colorectal cancer risk for an individual carrying the identified mutation is about 69%.
Researchers are concerned that the genetic risk for polyps and colon cancer may extend to many more people in the United States and not be recognized. The same mutation has been identified in other AFAP families who also share a genetic fingerprint called a haplotype that identifies individuals with common ancestors.
The Family
The couple was married in St. Nicholas, Somerset, England in 1615. A son born in 1615 is an ancestor of the New York family, and a daughter born in 1620 has descendents in the Utah family. Records show a daughter was married in Weymouth, Massachusetts in 1640.
Since the specific change has not been found in European families, it is assumed that either the husband or wife in the immigrant family was the first person to have the mutated gene and passed it along to his or her children and some of their descendents.
The Utah family or kindred (kindred #353) has been traced to a founding set of parents born in New York and Massachusetts in the 1790′s who moved to Utah as part of the Mormon immigration in 1850. More than 7000 individuals from this family are included in the Utah Population Database, which is linked to birth and death certificates in Utah and cancer registries in Utah and Idaho. The family history spans 9 generations.
The New York kindred (#439) includes 6 generations since the founding parents were born in 1830.
The current study included 490 members of the Utah family where 145 were mutation positive and 99 members of the New York family with 36 positive members. Information about the study group revealed:
- Average age for developing colon cancer was 58.
- The median number of polyps (adenomas) was 25
- One-third (36.6 percent) had fewer than 10 polyps
- Thirteen percent had no family members with more than 10 polyps
- Number of polyps didn’t appear to affect risk for developing colon cancer.
Mutations in APC gene
A variety of mutations in the tumor suppressor APC (adenomatosis polyposis coli) gene lead to both familial adenomatous polyposis (FAP) and attenuated adenomatous polyposis. FAP patients have hundreds of polyps lining their intestinal tracts often beginning in the teenage years. Lifetime risk of colorectal cancer, if there is no intervention, is 100 percent.
Patients with attenuated familial adenomatous polyposis or AFAP have fewer polyps (less than 100), tend to get them at when they are older, and usually have them in the upper part of the colon rather than throughout it. Lifetime risk of colon or rectal cancer is lower. For this particular mutation it is about 70 percent.
Genetic testing to identify risk
Because patients with fewer than ten polyps or who are diagnosed over age 50 may appear to be very much like people with sporadic colon cancer, it is challenging to identify mutation carriers, according to Deborah W. Neklason and the study authors at Huntsman Cancer Institute at the University of Iowa.
They suggest that the combination of young age at diagnosis and family history of colon polyps may identify individuals who carry an AFAP mutation. Specifically, they write,
A family history of colonic polyps or cancer in combination with any number of adenomatous polyps at a young age may be the key to recognizing potential AFAP patients from the vast number of individuals with sporadic adenomas. We suggest that genetic testing should be considered in any individual with a family history of 10 or more colonic adenomas based on the observation that 86.7% of mutation-positive individuals in this family would be captured with this criterion.
SOURCE: Necklason et al. Clinical Gastroenterology and Hepatology, Volume 6, Number 1, January, 2008.
An article about the study by Michael Kahn appears in Reuter’s Health.