A single variation on chromosome No. 8 may account for a significant proportion of colon cancer cases, according to a study by researchers at the Technion-Israel Institute of Technology and the University of Michigan.
The research, involving thousands of Israeli Jews and Arabs, has provided important new information on the genes that make a person more likely to develop this deadly cancer.
For a paper just published on-line in Cancer Biology and Therapy, the researchers worked as part of the the Molecular Epidemiology of Colorectal Cancer project, a Michigan-Israel collaboration that has searched for clues to colon cancer’s genetic roots for 10 years using samples from large numbers of Israelis correlated with their ancestry. The project is funded by the National Cancer Institute, with additional funding from the Irving Weinstein Foundation.
The link was found by detailed comparisons of genetic material from thousands of colon cancer patients and healthy individuals, and by evaluating the incidence of colon cancer among the immediate family members of colon cancer patients.
People who carry a specific genetic marker (variation) – called the C allele of rs10505477 – were found to be 23 percent more likely to have colon cancer than individuals without the marker. The researchers estimate that this single genetic variation might account for 14% of colorectal cancer cases in Israel, where colon cancer is a leading cause of cancer deaths.
Three other research teams have just reported similar findings in the journal Nature Genetics, having simultaneously found their way to the same small area of chromosome 8 – called 8q24 – in the search for colon cancer genetic links. The fact that these studies were performed among other populations suggests that this genetic marker is highly influential across ethnic groups.
The researchers compared the genetic makeup and family history of more than 1,800 colorectal cancer patients with that of 1,900 healthy people with the same breakdown of age, gender and ethnicity – either Ashkenazi Jews, Sephardi Jews or Arab/non-Jew. Samples of tumor tissue from many cancer patients were also tested.
The genetic link between the marker and colon cancer was especially strong among patients diagnosed with colon cancer before they were 50 years old.
Prof. Gad Rennert, the head of Israel’s Cancer Registry and a physician at Carmel Medical Center and Technion’s Medical School, said “the study of populations in Israel has been shown exceptionally fruitful in contributing to knowledge about the genetics of leading cancers. This is due to the unique characteristics of the population and our ability to study it in a representative manner.”
Unraveling the mysteries of the susceptibility to disease is moving rapidly since the publication of the complete sequence of the human genome in 2003.
Dr. Stephen Gruber, the co-leader of the Michigan-Israeli team and first author of the new paper, added: “The mystery of the relationship between our genetic code and disease is now starting to become clear, and many scientists are turning to the same chapter to find important clues to colorectal cancer.”
He and his colleagues plan to continue their effort to zero in on the genetic variations involved in cancer. Gruber said the new finding was particularly interesting when considered alongside recent discoveries in the genetics of prostate cancer and breast cancer.
“The same genetic region that predisposes to colon cancer has also recently been shown to be an important region predisposing to breast cancer and prostate cancer,” said Gruber, who is an associate professor of internal medicine and of human genetics in the University of Michigan Medical School and of epidemiology in the university’s School of Public Health. He also directs the cancer genetics program in the school’s Comprehensive Cancer Center, which focuses on inherited cancer risks.
“The specific genetic cause for this joint susceptibility to three different cancers has not yet been discovered, but several groups are working to close in on the mechanism that might cause it,” he said.
While there is not yet a screening test for the genetic variation that was pinpointed in the study, Gruber and his co-authors emphasize that genetic testing is available for other genetic variations linked to colorectal cancer. People with a strong family history of colon cancer, especially cases that began when relatives were younger than age 50, should get genetic counseling and have colonoscopies or other screening tests before they themselves turn 50.
Colon cancer is one of the most common cancers in Israel and the US; the good news is that it is largely preventable with early screening, said Gruber. Although most cancers are not “inherited,” some families are particularly susceptible and may benefit from early detection or other risk reduction strategies.
Genetic counseling and screening can already help to identify two common conditions associated with familial colon cancer risk – familial adenomatous polyposis and Lynch Syndrome, which usually causes cancer to develop either in the colon or the uterus.