The Ashkenazi-Adiponectic Connection
Wed, 10/29/2008
Staff Writer
As a month-long string of food-consuming holidays comes to an end, Jews across the world will unbutton their waistbands and perhaps hop on a treadmill to avoid the looming threat of obesity that afflicts so many Jewish families. But those with a genetic predisposition to obesity may now have another related monster to fear — colorectal cancer. According to researchers, Ashkenazi Jews have a higher risk of developing colorectal cancer than most other tight-knit, rather homogeneous ethnic groups. Scientists have identified four markers — called “snips” — of a certain chromosome that may be correlated with both obesity and colorectal cancer risks particularly within this Jewish subgroup. “It’s the first time that a gene linked with obesity and fat cells is linked with colorectal cancer risk,” said Boris Pasche, one of the leading researchers and the newly appointed director of hematology and oncology at the University of Alabama – Birmingham’s Comprehensive Cancer Center. Out of the four snips, two are thought to decrease and two are thought to increase the presence of the hormone adiponectin, a chemical secreted by fat cells into the bloodstream. When adiponectin levels are low, it seems that patients may have a higher risk of colon cancer, as well as diabetes and obesity, according to team member Virginia Kaklamani, an assistant professor of hematology and oncology at Northwestern University’s Feinberg School of Medicine. High levels of adiponectin may produce the opposite — and more desired — effect. “If you inherit that region of the chromosome — of adiponectin — it influences your risk of colorectal cancer,” Pasche said. “You can have a low level, and that predisposes you to colon cancer,” Kaklamani added. Drs. Virginia Kaklamani and Boris Pasche were among a team of doctors and researchers who performed two studies that have led them to this conclusion. The team released its findings, along with details about each of the studies  in the Oct. 1 edition of The Journal of the American Medical Association, “Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colorectal Cancer Risk”. Two case-controlled studies, one based exclusively among Ashkenazi Jews in New York City and the other rooted in a mixed ethnicity sample in Chicago. In the first study, participants included 441 patients diagnosed with colorectal cancer and 658 controls. The second study included 199 cancer patients paired with 199 controls, each of whom matched a patient in sex, age and ethnicity. Among the homogeneous Ashkenazi population, the doctors identified four snips associated with colorectal cancer risk, and in the Chicago study — which largely consisted of African Americans, Hispanics, Asians and some Caucasians — they identified only one snip associated with cancer risk, according to Pasche. Three of the four chromosomal snip correlations existed solely in the first study. The Ashkenazi Jewish subgroup exhibited some genetic mutations that rarely exist among non-Jews. “The adiponectin snip was found to have an effect with respect to colorectal cancer risk among Ashkenazi Jews, and the risk was confirmed in the second study, in which the majority were non-Jews,” Pasche said. For the time being, doctors are considering the possibility that adiponectin plays a part in increasing and decreasing the risk of colorectal cancer, and future studies will verify whether or not this emerging hypothesis is true. “This is definitely something we would like to validate among another group of Ashkenazi Jews,” Pasche said. In the next study, Pasche would like to use a concentrated population of Ashkenazi Jews, presumably from New York or Israel, whom he would match with Jewish controls of the exact same ages and genders, as they did in the Chicago trial. For now, Pasche recommends that Jews and non-Jews alike continue to have regular cancer screenings from age 50, and those with family history should begin even earlier. This start date should be reduced by 10 years for both men and women who have a family history of colorectal cancer. If anyone in the family has been diagnosed with the cancer before he or she reaches 50, screenings for other family members should occur 10 years before they reach that age. In addition to administering regular colonoscopies, doctors can easily identify the genetic mutation by performing a simple blood test, according to Kaklamani. With this ability and future technological developments, she hopes that scientists might one day be able to inject the adiponectin hormone into a patient’s bloodstream, to combat his or her genetic predisposition of developing colorectal cancer. But that’s not happening any time soon, she warned. “We’re far from that,” Kaklamani said. “From cells to people it takes a while.”