Periodontal Disease And Pancreatic Cancer Linked

: Cancer / Oncology News Article Date: 19 Jan 2007 - 9:00 PDT  also in Lancet Oncology

Pancreatic cancer is the fourth leading cause of cancer death in the U.S.; more than 30,000 Americans are expected to die from the disease this year. It is an extremely difficult cancer to treat and little is known about what causes it. One established risk factor in pancreatic cancer is cigarette smoking; other links have been made to obesity, diabetes type 2 and insulin resistance. In a new study, researchers at the Harvard School of Public Health (HSPH) and Dana-Farber Cancer Institute found that periodontal disease was associated with an increased risk of cancer of the pancreas. The study will appear in the January 17, 2007 issue of the Journal of the National Cancer Institute.

"Our study provides the first strong evidence that periodontal disease may increase the risk of pancreatic cancer. This finding is of significance as it may provide some new insights into the mechanism of this highly fatal disease," said lead author Dominique Michaud, assistant professor of epidemiology at HSPH.

Periodontal disease is caused by bacterial infection and inflammation of the gums that over time causes loss of bone that supports the teeth; tooth loss is a consequence of severe periodontal disease. Two previous studies had found a link between tooth loss or periodontitis and pancreatic cancer, but one consisted of all smokers and the other did not control for smoking in the analysis, and therefore no firm conclusions could be drawn from these studies.

Data for the new study came from the Health Professionals Follow-Up Study, which began in 1986 and includes 51,529 U.S. men working in the health professions. Participants respond to questionnaires about their health every two years. After analyzing the data, the researchers confirmed 216 cases of pancreatic cancer between 1986 and 2002; of those, 67 reported periodontal disease.

The results showed that, after adjusting for age, smoking, diabetes, body mass index and a number of other factors, men with periodontal disease had a 63% higher risk of developing pancreatic cancer compared to those reporting no periodontal disease. "Most convincing was our finding that never-smokers had a two-fold increase in risk of pancreatic cancer," said Michaud.

One possible explanation for the results is that inflammation from periodontal disease may promote cancer of the pancreas. "Individuals with periodontal disease have elevated serum biomarkers of systemic inflammation, such as C-reactive protein, and these may somehow contribute to the promotion of cancer cells," she said.

Another explanation, according to Michaud, is that periodontal disease could lead to increased pancreatic carcinogenesis because individuals with periodontal disease have higher levels of oral bacteria and higher levels of nitrosamines, which are carcinogens, in their oral cavity. Prior studies have shown that nitrosamines and gastric acidity may play a role in pancreatic cancer.

Michaud, senior author Charles Fuchs, a gastrointestinal oncologist at Dana-Farber, and their colleagues believe that further studies should be done to investigate the role of inflammation from periodontal disease in pancreatic cancer. However, Michaud notes that the underlying mechanisms for this association are speculative at this point. "More research is needed both to confirm this finding in other populations and also to explore the role of inflammation in this particular cancer," she said.

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Link Between Chronic Inflammation And Cancer Confirmed     J. Clin. Invest.  doi:10.1172/JCI35073.  09 Jun 2008    According to scientists at the Massachusetts Institute of Technology, chronic inflammation of the intestine or stomach has been linked to DNA damage and thus increased cancer risk. These results were released on June 2, 2008 in the Journal of Clinical Investigation (JCI). Inflammation can be caused by many factors, including infectious agents such as Helicobacter pylori and Hepatitis C, which are already known to increase cancer risk in the stomach and liver, respectively. The inflammatory response produces cytokines, the chemicals in the immune response that encourage cell proliferation and suppress apoptosis, which can also contribute to an increased risk of cancer. In most normal situations, damage induced to DNA during an inflammatory response is repaired by the cell's internal error correction system -- but if this is not functioning properly, there is a higher chance that mutation will occur, increasing the risk of cancer. Knowing the connection between these factors and cancer can help doctors better guide patients who might be at risk for inflammation induced cancers. "That variation could influence the susceptibility of individuals and how they are going to respond to a chronic inflammation response," said senior author Leona Samson, director of the CEHS. By performing two separate studies, the team discovered that chronic inflammation in mice generally increased the development of tumors. This was tested additionally using mice who were already less able to repair DNA damage and thus more susceptible to cancerous mutations. While this was long hypothesized, these studies help confirm the idea that inflammation can be linked to cancer. "It's something that was expected but it was never formally proven," said lead author Lisiane Meira, research scientist in MIT's Center for Environmental Health Sciences (CEHS). In the JCI study, colon inflammation was induced using a chemical compound that mimics a human colitis. This induced a higher rate of cancer. According to Meira: "Lo and behold, the DNA repair deficient mice were more susceptible." A second study, in collaboration with James Fox, director of the Division of Comparative Medicine at MIT, and one of his students, Chung-Wei Lee, meant to solidify the first. In this, mice were infected with H. pylori, and those lacking the proper DNA repair mechanisms were more likely to have pre-cancerous regions in the stomach. The latter study is further related to another piece published by Fox, which showed that treating infection with this bacterium quicly could prevent cancer development.  These results indicate that individuals who are less able to perform DNA damage with chronic inflammation, such as ulcerative colitis, are more susceptible to cancer than others, according to Meira. However, there is another effect of inflamation that they postulate might influence this -- during the inflammatory response to infection, immune cells like macrophages and neutrophils excrete oxygen and nitrogen species that might damage DNA. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice Lisiane B. Meira, James M. Bugni, Stephanie L. Green, Chung-Wei Lee, Bo Pang, Diana Borenshtein, Barry H. Rickman, Arlin B. Rogers, Catherine A. Moroski-Erkul, Jose L. McFaline, David B. Schauer, Peter C. Dedon, James G. Fox and Leona D. Samson

                      

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INFLAMMATION MARKER PREDICTS COLON CANCER

Johns Hopkins Medicine
February 3, 2004

C-reactive protein (CRP) -- a marker of inflammation circulating in the blood already associated with increased risk of heart disease -- can also be used to identify a person's risk of developing colon cancer, according to a Johns Hopkins study.

Results of the study, published in the Feb. 4 issue of The Journal of the American Medical Association, showed that over an 11-year period, people with higher levels of CRP in their blood (a median of 2.44 milligrams per liter) were more likely to develop colorectal cancers than those with low levels of CRP (a median of 1.94 mg/L).

"Higher levels of C-reactive protein are linked to an increased risk of several apparently distinct, chronic diseases: heart disease, stroke, diabetes, and now colon cancer," says Thomas "Tate" P. Erlinger, M.D., M.P.H., lead author of the study and an assistant professor of medicine at Johns Hopkins. "However, it's not clear yet how or whether measuring C-reactive protein would fit into current screening and prevention strategies for colorectal cancer. Further studies should help answer these
questions and help clarify the mechanism by which inflammation increases the risk of cancer."

Erlinger and colleagues studied the records of 22,887 adults who participated in the CLUE II study, conducted in Washington County, Md., looking to identify those who developed colon or rectal cancer. In the CLUE II investigation, named for its campaign, "Give Us A Clue to Cancer and Heart Disease" and started between May and October 1989, study volunteers provided a blood sample and completed a brief health
questionnaire. They since have been followed by additional questionnaires and tracking data.

Comparing the CLUE II medical records with the Washington County and Maryland State cancer registries, the Hopkins team noted 172 people who were diagnosed with either colon or rectal cancer following their initial date of blood draw through December 2000. Of these, 131 had colon cancer and 41 had rectal cancer. Researchers then compared the health records of each of these individuals with those of up to two healthy volunteers who joined the study at the same time, using the healthy volunteers as a control group.

Median CRP levels at baseline were higher among people who subsequently developed colon cancer (2.69 mg/L) than among those who remained free of disease (1.97 mg/L). By contrast, CRP concentrations were not significantly different between cases of rectal cancer (1.79 mg/L) and the controls (1.81 mg/L).

The study also found that:

* The odds of developing colorectal cancers increased progressively with higher concentrations of CRP. Overall, people in the highest fourth of CRP had twice the risk of developing colorectal cancer, and 2.5 times the risk of developing colon cancer, as those in the lowest fourth.

* Among nonsmokers, those in the highest fourth of CRP were 2.5 times as likely to develop colorectal cancer, and 3.5 times as likely to develop colon cancer, as those in the lowest fourth.

* Those who had taken either aspirin or nonsteroidal anti-inflammatory agents within the 48 hours prior to blood draw had a reduced risk of colorectal cancer.

* The association of inflammation with colon cancer was unrelated to diabetes, going against the belief that diabetes acts as the mediator between inflammation and cancer risk.

Erlinger notes that while these results should apply to the general population, most of the study population was Caucasian, so further studies should look at a more diverse group.

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Associated press release:

Gum disease may increase the risk of developing cancer, researchers said
on Tuesday.

Male health professionals with a history of gum disease in a
long-running study had a 14 percent higher overall risk of developing
cancer, they said.

"After controlling for smoking and other risk factors, periodontal
disease was significantly associated with an increased risk of lung,
kidney, pancreatic and hematological (blood) cancers," Dr. Dominique
Michaud of the Imperial College London and colleagues wrote in the
journal Lancet Oncology.

This higher overall risk persisted even in people who had never smoked.

Gum or periodontal disease is an infection of the tissues surrounding
and supporting the teeth. Prior studies have suggested people with
periodontal disease are more likely to develop heart disease and diabetes.

People with gum disease have inflammation in their blood and
inflammation also has been linked with cancer. But this could simply
mean that whatever causes the inflammation may also cause gum disease
and cancer. Michaud and colleagues wanted to see if gum disease
increases the risk of cancer.

They used data from a large study of male doctors and other health
professionals aged 40 to 75. The study was started in 1986 at Harvard
University.

Nearly 50,000 men filled out health surveys and were followed for more
than 17 years. The survey included information on gum disease and bone
loss as well as number of teeth and tooth loss.

More than 5,700 of the men developed cancer, excluding cases of
non-melanoma skin cancers and non-aggressive prostate cancer. The
researchers found that men who had gum disease had 14 percent higher
cancer risk compared to those who did not.

The risks were higher depending on the type of cancer.

Those with history of gum disease had a 36 percent higher risk of lung
cancer, a 49 percent higher risk of kidney cancer, a 54 percent higher
risk of pancreatic cancer and a 30 percent higher risk of having a blood
cancer (such as non-Hodgkin lymphoma, leukemia or multiple myeloma)
compared to men who did not have a history of gum disease.

In those who never smoked, gum disease was linked with a 21 percent
increase in overall cancer risk and a 35 percent higher risk of blood
cancers. They found no association for lung cancer in this group.

Men who had fewer teeth (0 to 16) at the start of the study had a 70
percent higher risk of lung cancer compared with individuals with more
teeth (25 to 32) at the start of the study but this may be linked with
smoking.

"The increased risks noted for hematological, kidney, and pancreatic
cancers need confirmation but suggest that gum disease might be a marker
of a susceptible immune system or might directly affect cancer risk,"
Michaud said in a statement.

They said it is premature to suggest that good oral hygiene can have any
effect at preventing cancer but said periodontal disease should
nevertheless be treated.

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