Colorectal Cancer in Younger Patients
With 655,000 deaths worldwide per year from colorectal cancer, it is the fourth most common form of cancer in the United States. Although it generally occurs in patients 60 and up, younger patients have been known to develop the cancer with no family history of it, and until now, researchers have been bemused as to why this occurs. A recent study has uncovered a link involving telomeres and an increased risk for colorectal cancer in younger age groups that could help determine what forms of treatment may be necessary.
A telomere is a region of repetitive DNA at the end of a chromosome, which protects the end of the chromosome from deterioration – they’re similar to plastic coverings that are found on shoelaces. Telomeres shorten in part because of the end replication problem that is exhibited during DNA replication in eukaryotes only. Shortened telomeres have been associated with an increased risk of cancer development, according to Lisa A. Boardman, M.D., associate professor of medicine, Mayo Clinic, Rochester, Minn.
Boardman and colleagues ventured out in hopes of finding evidence of biological aging in people who develop colorectal cancer at a young age. The ambitious team strived to determine what exactly caused these young patients to develop a disease that commonly occurs with people in their 60s and 70s.
"We anticipated that we would see some people who had young-onset colon cancer and shorter telomeres compared to people of the same age group who did not have cancer," which Boardman was quoted as saying.
Boardman was surprised, nonetheless, to find a group with long telomeres. "Even for people their age, their telomeres were longer than you'd expect for healthy people. This suggests that there may be two different mechanisms that affect telomere length and that set up susceptibility to cancer," she said.
The team of researchers carefully measured peripheral blood leukocyte length in 772 patients with diagnosis of microsatellite stable colorectal cancer. All patients participating in the study were both younger than 60 years of age at diagnosis and had no previous history of chemotherapy. This group’s telomere length was compared with 1,660 nonrelated, age-matched, healthy controls.
The results showed that patients with the longest telomeres – those patients in the 95th percentile of telomere length – were 30 percent more likely to develop colorectal cancer than those in the 50th percentile. Boardman added that the individuals with the shortest and the longest telomere lengths were at an increased risk for colorectal cancer.
In due course, there may be two specific groups of colorectal cancer in young-onset patients. The first involves telomere shortening, and this subset of young-onset colorectal cancer patients who have accelerated aging. The subsequent may be a distinct group of patients with longer telomeres.
Future studies will examine the telomere maintenance genes in the peripheral blood DNA. Researchers are currently in the process of comparing the telomere lengths in the peripheral blood DNA with that in the tumor. This is being done in an effort to determine if these subsets of patients with younger-onset colorectal cancer have tumors that are mechanistically distinct.
"It may be that if they truly go through different mechanisms in the development of cancer, then they may respond to different types of treatment and have a different molecular profile," concluded Boardman.
SOURCE: American Association For Cancer Research conference on Colorectal Cancer: Biology to Therapy, 27 – 30 October 2010