Study shows how high-fat diets increase colon cancer risk
Epidemiologists have long warned that, in addition to causing obesity, eating too much fat and sugar puts a person at greater risk for colon cancer. Now, researchers at Temple University have established a link that may explain why.
The findings, “Epigenetic Differences in Normal Colon Mucosa of Cancer Patients Suggest Altered Dietary Metabolic Pathways,” were published in the March issue of the American Association for Cancer Research’s journal, Cancer Prevention Research.
“There have always been questions about why things like diet and obesity are independent risk factors for colon cancer,” said Carmen Sapienza, professor of pathology in Temple’s Fels Institute for Cancer Research and Molecular Biology, the study’s lead author. “This study suggests how and why high fat diets are linked to colon cancer.”
The researchers compared colon tissue in non-colon cancer patients with normal colon tissue in patients with the disease. In the normal tissue from patients with colon cancer, they found that epigenetic marks on genes involved in breaking down carbohydrates, lipids and amino acids - abundant in the fatty Western diet - appeared to have been retrained. Epigenetic marks are chemical modifications that serve as on/off switches for many genes.
“These foods are changing the methylation patterns on a person’s insulin genes so that they express differently, pumping out more insulin than the body requires,” said Sapienza. “In people that have colon cancer, their glucose metabolic pathways and insulin signaling pathways are running at completely different levels than people who don’t have colon cancer.”
Sapienza said that cancer cells love insulin and studies have shown that tumors feed off of insulin. “Insulin is only supposed to be expressed in your pancreas, so having this extra insulin is bad,” he said.
Colorectal cancer is a disease in which cells in the colon or rectum become abnormal and divide without control, forming a mass called a tumor. (The colon and rectum are parts of the body’s digestive system, which takes up nutrients from food and water, and stores solid waste until it passes out of the body.)
Colorectal cancer cells may also invade and destroy the tissue around them. In addition, they may break away from the tumor and spread to form new tumors in other parts of the body.
Colorectal cancer is the third most common type of non-skin cancer in men (after prostate cancer and lung cancer) and in women (after breast cancer and lung cancer). It is the second leading cause of cancer death in the United States after lung cancer. Although the rate of new colorectal cancer cases and deaths is decreasing in this country, an estimated 141,210 new cases of colorectal cancer and 49,380 deaths from this disease are expected to occur in 2011.
Sapienza pointed out that people don’t usually get colon cancer until the age of 50 or older, so it is unclear when the epigenetic modification of the genes begins.
Jewish Genetics and Colorectal Cancer
There are several identified genetic factors known to be associated with colorectal cancer. Various studies have looked at the ethnic distribution of such mutations. As with many genetic disorders, ethnic specific mutations for colorectal cancer have been seen in different populations, such the Finnish and Swedish populations among others. There has long been a clinical impression that colorectal cancer is more common in Ashkenazi Jews with some estimates putting their lifetime risk as high as 15% (Feldman GE Isr Med Assoc J 2001; 3:341–6). If this is true, it is likely due to a combination of multiple factors including incidence of predisposing medical conditions, environment/diet and genetics. While some of the known genetic factors have been associated with Ashkenazi ancestry, none of them is enough to explain a higher incidence of colorectal cancer in Ashkenazi Jews.
Being Ashkenazi Jewish
People with an Ashkenazi Jewish background have a higher risk of bowel cancer. This may be due to a gene fault that is more common in this group. About 1 in 10 Ashkenazi Jews have a faulty gene called I1307K. We don’t know yet if it is this gene that causes the increase in bowel cancer. People in this ethnic group also have a higher risk of breast cancer because they are more likely to carry one of the breast cancer gene faults – BRCA1 or BRCA2.
“The hypothesis is that the changes in the metabolic pathways happen first, and once they occur, if any kind of mutation happens that causes a cancerous polyp, you are going to feed it through this excess insulin,” he said.
Sapienza said this study provides the first evidence of widespread epigenetic modification of metabolic pathway genes occurring in healthy colon tissue.
The researchers theorize that if the modification found in healthy colon tissue could also be found in other healthy tissues in the body, they might be used to diagnose or determine the likelihood of colon cancer by through a saliva or blood test in addition to a colonoscopy.