Lineage of Gene Tied to Cancer Is Traced

A significant fraction of colorectal cancers in the United States may be caused by a defective gene brought to this country by a German immigrant about 13 generations ago, according to researchers at Ohio State University.

The mutant gene causes a condition called hereditary nonpolyposis colon cancer, or HNPCC. People with the condition have an 80% to 85% risk of colorectal cancer; women with the gene also have a 56% risk of endometrial cancer and a 12% risk of ovarian cancer.

An estimated 147,500 cases of colorectal cancer occur in the United States each year, about a quarter of them hereditary. NHPCC is thought to be responsible for a major portion of the hereditary cases.

Dr. Albert de la Chapelle of Ohio State and his colleagues identified 566 individuals in nine families who are direct descendants of a German couple who immigrated to Pennsylvania in 1727.

The team reported in this week’s issue of the Journal of the American Medical Assn. that either the husband or wife carried a mutation in a gene called MSH2. The mutation results in the loss of about a third of the gene, producing the high risk of cancer.

The couple had 11 children, and the team thinks they may have a much larger number of descendants than those identified in the study.

Using a newly developed test for the mutated gene, the team has so far studied 137 of the 566 family members and found that 44.5% of them carry the mutation and thus should undergo regular checkups for colorectal, endometrial and ovarian cancer.

They urged people with a family history of these cancers to contact a genetic counselor to determine whether they should be tested for the gene.