Drugs for Inflammatory Bowel Might Increase Cancer Risk

Long-term use of thiopurines bears further study, researchers say

The use of thiopurine drugs to treat inflammatory bowel disease (IBD) increases the risk of cancers related to viral infection, according to a new study.

IBD includes Crohn's disease and ulcerative colitis. Thiopurine drugs are used to suppress the immune system in order to maintain remission in IBD patients.

For this study, French researchers analyzed data on 19,486 IBD patients (60 percent with Crohn's and 40 percent with ulcerative colitis or unclassified IBD) who were followed for a median of 35 months.

At the start of the study, 30 percent of patients were taking thiopurines, 14 percent had discontinued them, and 56 percent had never received thiopurines. During the study, 23 patients developed malignant lymphoproliferative disorders (LD) -- cancers that are associated with viral infection, particularly those linked to Epstein Barr virus (EBV) infection.

Of the 23 patients with LD, 22 had non-Hodgkin's lymphoma and one had Hodgkin's lymphoma. Incidence rates of LD were 0.90 per 1,000 patient-years in those receiving thiopurines, 0.20 per 1,000 patient-years in those who'd discontinued the drugs, and 0.26 per 1,000 patient-years in those who'd never taken thiopurines.

The researchers calculated that IBD patients taking thiopurines had a more-than-five-fold increased risk compared to those who'd never received the drugs. Older patients, men, and those who'd had IBD for longer were also at increased risk of LD.

"Extrapolating our results, the absolute cumulative risk of (LD) in young patients receiving a 10-year course of thiopurines remains low (less than 1 percent) and does not undermine the positive risk-benefit ratio of these drugs. For elderly patients and unlimited treatment periods, the question should be addressed in dedicated studies," wrote Laurent Beaugerie, a professor at Hospital Saint-Antoine, Paris, and colleagues.

The study appeared online Monday and in an upcoming print issue of The Lancet.

"Although we recognize the slightly increased risk of lymphoma, these agents will probably remain one of the cornerstones of treatment. Nonetheless, physicians should be cautious when prolonged combined and deep immunosuppression is needed to achieve disease control," Dr. Geert D'Haens, of the Imelda GI Clinical Research Centre and University Hospital Gasthuisberg in Belgium, and Dr. Paul Rutgeerts, University Hospital Gasthuisberg, wrote in an accompanying editorial.

SOURCE: The Lancet, news release, Oct. 18, 2009

Lactose Intolerance

Lactose intolerance is the inability or insufficient ability to digest lactose, a sugar found in milk and milk products. Lactose intolerance is caused by a deficiency of the enzyme lactase, which is produced by the cells lining the small intestine. Lactase breaks down lactose into two simpler forms of sugar called glucose and galactose, which are then absorbed into the bloodstream.

Not all people with lactase deficiency have digestive symptoms, but those who do may have lactose intolerance. Most people with lactose intolerance can tolerate some amount of lactose in their diet.

People sometimes confuse lactose intolerance with cow milk allergy. Milk allergy is a reaction by the body’s immune system to one or more milk proteins and can be life threatening when just a small amount of milk or milk product is consumed. Milk allergy most commonly appears in the first year of life, while lactose intolerance occurs more often in adulthood.

What causes lactose intolerance?

The cause of lactose intolerance is best explained by describing how a person develops lactase deficiency.

Primary lactase deficiency develops over time and begins after about age 2 when the body begins to produce less lactase. Most children who have lactase deficiency do not experience symptoms of lactose intolerance until late adolescence or adulthood.

Researchers have identified a possible genetic link to primary lactase deficiency. Some people inherit a gene from their parents that makes it likely they will develop primary lactase deficiency. This discovery may be useful in developing future genetic tests to identify people at risk for lactose intolerance.

Secondary lactase deficiency results from injury to the small intestine that occurs with severe diarrheal illness, celiac disease, Crohn’s disease, or chemotherapy. This type of lactase deficiency can occur at any age but is more common in infancy.

Who is at risk for lactose intolerance?

Lactose intolerance is a common condition that is more likely to occur in adulthood, with a higher incidence in older adults. Some ethnic and racial populations are more affected than others, including African Americans, Hispanic Americans, American Indians, and Asian Americans. The condition is least common among Americans of northern European descent.

Infants born prematurely are more likely to have lactase deficiency because an infant’s lactase levels do not increase until the third trimester of pregnancy.

What are the symptoms of lactose intolerance?

People with lactose intolerance may feel uncomfortable 30 minutes to 2 hours after consuming milk and milk products. Symptoms range from mild to severe, based on the amount of lactose consumed and the amount a person can tolerate.

Common symptoms include

•abdominal pain
•abdominal bloating
•gas
•diarrhea
•nausea

What are the complications of Crohn’s disease?

Intestinal blockage can occur in people with Crohn’s disease. Blockage occurs because the intestinal wall thickens or swells from inflammation and scar tissue. Ulcers can also cause tunnels to form through the inflamed areas of the intestine or even the healthy parts. These tunnels are called fistulas. Sometimes pockets of infection, called abscesses, can form in and around the fistulas. Fistulas can be treated with medicine, but sometimes surgery is needed.

People with Crohn’s disease often don’t get the nutrients they need. If you have Crohn’s disease, you may not get enough protein, vitamins, or calories in your diet. If you aren’t getting nutrients, it may be because you

-have an upset stomach that keeps you from eating enough
-may be losing protein in the intestine
-may not be able to absorb nutrients from your food

Other problems that some people with Crohn’s disease suffer from are arthritis, skin problems, swelling in the eyes or mouth, kidney stones, and gallstones.

UF researchers find triggers in cells’ transition from colitis to cancer

University of Florida researchers have grown tumors in mice using cells from inflamed but noncancerous colon tissue taken from human patients, a finding that sheds new light on colon cancer and how it might be prevented.

Scientists observed that cancer stem cells taken from the gastrointestinal system in patients with a chronic digestive disease called ulcerative colitis will transform into cancerous tumors in mice.

The finding, now online and to be featured on the cover of the Thursday (Oct. 15) issue of Cancer Research, may help explain why patients with colitis have up to a 30-fold risk of developing colon cancer compared with people without the disease.

New understanding of the link between colitis and cancer could lead to diagnostic tests that would evaluate tissue taken from patients with colitis for signs of cancer stem cell development, thereby identifying patients who may be at greater risk for cancer.

“Ultimately it would be great if we could prevent colitis or treat colitis so it never gets to the cancerous stage,” said UF colorectal surgeon Dr. Emina Huang, who is a member of the Program in Stem Cell Biology and Regenerative Medicine at UF’s McKnight Brain Institute and the UF College of Medicine.

Although colonoscopy is very effective in screening and preventing colon cancer for most people, for patients with colitis no diagnostic tests work well because the inflamed tissue makes identification of precancerous changes difficult.

According to the Crohn’s and Colitis Foundation of America, approximately 700,000 people have colitis in the United States. The National Cancer Institute estimates that cancer of the colon and rectum will claim the lives of about 50,000 people this year.

UF scientists gathered colitic tissue from humans and chemically screened it for colon cancer stem cells, also called tumor initiating cells. These cells were then isolated and monitored in mice to see if tumors would grow.

Huang said these findings shed light on that fact that it may not be just the cancer “seed” cell, but the “soil” — in this case inflamed colon tissue — that plays a role in the development of cancer.

“Is it the seed, is it the soil or is it their interaction?” she said. “We think probably both, but now we have a new way to look at it and a new method of attack.”

Dr. B. Mark Evers, a professor and vice chair of surgery at the University of Kentucky College of Medicine, said the study emphasizes the emerging role of the surrounding inflammatory tumor microenvironment on tumor growth and subsequent metastasis.

“Dr. Huang and her group have identified a potentially important mechanism to explain why long-standing inflammation of the colon predisposes patients to the development of cancer,” said Evers, who is director of the Lucille P. Markey Cancer Center in Lexington, Ky.

To further understand the role of the “seed” and “soil” interaction, UF researchers paired colon cancer stem cells with normal, colitic and cancerous human cells taken from the scaffolding layer of the large intestine. The cells were implanted into mice to analyze growth rates. The combination of tumor cells and normal scaffolding tissue cells grew at the slowest rate. Tumor cells paired with cancerous tissue grew at an intermediate rate, and tumor cells paired with the colitic tissue grew at the fastest rate.

Huang said they found heightened levels of two immune system hormones called interleukin-6 and interleukin-8 in the cells from the colitic and cancerous tissues, which had the faster growth rates.

When UF researchers decreased the expression of these hormones within the cells, the tumor growth drastically decreased. When the hormones returned, the tumors began to grow again.

“We don’t understand the transition at the molecular level so we are trying to figure out what we can target to interfere, intervene or inhibit that transformation of the benign colitic cells,” she said. “The thought is if we can create a therapy to decrease function of these hormones, we may be able to prevent or inhibit cancer growth.”

Clinical trials looking at the role of one of these hormones in humans are under way in England, Huang said.

This article is a reprint of http://news.ufl.edu/2009/10/12/colon-cancer/ The time or date displayed reflects when an article was added to Google News Oct. 12

Gene Variant Raises Crohn's Disease Risk

Common Gene Linked to Inflammatory Bowel Disease Susceptibility

A gene variant common in whites is linked to Crohn's disease, an intriguing new study suggests.

Crohn's disease is an inflammatory bowel disease (IBD). In IBD, the delicate balance of the gut ecosystem is disrupted by an excessive inflammatory immune response.

People who carry the gene variant make less of an inflammation-dampening enzyme called CD39. This may tip the immune balance toward IBD, suggest David J. Friedman, MD, of Beth Israel Deaconess Medical Center, and colleagues.

"Our data indicate that CD39 [gene variants] are associated with inflammatory bowel disease in humans," the researchers conclude. Their report appears in the Sept. 29 issue of the Proceedings of the National Academy of Sciences.

The researchers fed mice a chemical that gives them IBD. Specially bred mice lacking the CD39 gene had worse IBD than mice with a normal version of the gene.

All humans have a CD39 gene. But some have a version of the gene linked to lower CD39 levels. Friedman and colleagues identified a genetic marker for low CD39 production. They then looked for this marker in 1,748 patients with Crohn's disease and in 2,936 people without IBD.

They found that the genetic marker was significantly more common in people with Crohn's disease. Moreover, people without IBD were more likely to carry two copies of the high-CD39 gene, while those with Crohn's disease were more likely to carry two copies of the low-CD39 gene.

Genetics are not destiny. Not everyone with the low-CD39 gene has or will have IBD. Even having two copies of the gene only increases a person's risk of Crohn's disease by 27%.

But since about 40% of whites of European ancestry carry at least one copy of the gene, its effects across the entire population should be quite large.

Moreover, the gene may affect more than IBD. It's also linked to kidney disease in people with diabetes and to blood clots in the arteries.

The researchers plan to perform more extensive studies of the role of the CD39 gene in IBD.

This article is a reprint of http://www.webmd.com/ibd-crohns-disease/news/20090928/gene-variant-raises-crohns-disease-risk The time or date displayed reflects when an article was added to Google News Sep. 29

Colon cancer risks: High-fat diet, family history play role

Cancers of the colon and rectum will affect one of 17 people. These cancers of the lower digestive tract are the second-leading cause of cancer deaths in the United States and Europe. Colorectal cancers are treatable if detected in the early stages. Experts recommend screening for colon cancer beginning at age 50 and screening by age 45 for those with a family history of cancer or those of African-American heritage.


Current screening tests include annual testing of the stool for blood and colonoscopy. Colonoscopy involves using a scope with a tiny camera to look at the lining of the large intestine.

Researchers in Germany are also working on a new blood test that may help find colon cancer. The lining of the intestinal tract can develop small pre-cancerous growths called polyps which can usually be removed during a screening colonoscopy. If these polyps are not removed, they can become cancerous.
Risk factors for developing colon cancer are:

•Family history of colon cancer or colon polyps.

•Low-fiber, high-fat diet. Colorectal cancers are associated with a diet high in fat and calories that lacks enough fiber or roughage. Add more fruits and vegetables and whole grains to your daily diet. Limit fried and fatty foods. Cut back on added fats such as butter, margarine, salad dressing, mayonnaise, gravies and sauces.

•A sedentary lifestyle. Regular physical activity can reduce the risk for colon cancer. Experts recommend daily activity of at least one hour. Walking, biking, swimming, chair aerobics and most sports are great.

•Diabetes and obesity. Insulin resistance and excess weight increase the risk of developing colon cancer and the risk of death from it.

•Smoking and alcohol use.

•Inflammatory intestinal conditions. Chronic intestinal problems like Crohn's disease or ulcerative colitis can increase risk.

•Older age. About 90 percent of all colon cancer occurs in people over age 50.
Many people do not experience any unusual symptoms. Make an appointment to see your health care provider if you notice any change in your bowel habits that lasts more than two weeks, blood in your stool or persistent abdominal cramping or gas. If you have any unplanned weight loss, weakness or fatigue, get a checkup.

This article is a reprint of
http://www.clarionledger.com/article/20090929/COL0803/909290355/1292/health/Colon-cancer-risks--High-fat-diet--family-history-play-role The time or date displayed reflects when an article was added to Google News Sep. 29