A2 AASHIRWAD, II CROSS LANE, LOKHANDWALA COMPLEX, ANDHERI (WEST), MUMBAI 400053, INDIA

A humble toothbrush could be a powerful pancreatic cancer prophylaxis, suggest results of an observational study that associated periodontal disease with the malignancy.

Men with periodontitis and tooth loss, or both, had an overall 64% greater risk of cancer of the pancreas than men with good oral health, showed data from Health Professionals Follow-Up Study.

The strength of the association was underlined by the finding that men with periodontal who never smoked cigarettes -- one of the few known risk factors for pancreatic cancer -- had a more than two-fold greater risk for the malignancy, reported epidemiologist Dominique Michaud, Sc.D., of the Harvard School of Public Health, and colleagues

"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 Dr. Michaud, in the Jan. 17 issue of the Journal of the National Cancer Institute.

The investigators hypothesized that systemic inflammation may play a key role in the pathogenesis of pancreatic cancer, an idea supported by the finding that people with periodontal disease have elevated levels of inflammatory markers in serum, most notably C-reactive protein.

Alternatively, carcinogenic nitrosamines and high levels of oral bacteria found in the mouths of people with periodontal might interact with gastric acids to promote the development of pancreatic cancer, Dr. Michaud said.

She and colleagues extracted data on periodontal disease from the Health Professionals Study, which followed a cohort of more than 51,000 male health professionals from the ages of 40 to 75 years at baseline in 1986.

The baseline questionnaire asked participants whether they had ever had periodontal disease with bone loss, and the participants were asked to report any tooth losses on biennial follow-up questionnaires.

During 16 years of follow-up, 216 men out of the original 51,529 in the study cohort were diagnosed with incident pancreatic cancer.

The authors created Cox proportional hazard models to estimate relative risk and control for potential confounders, including smoking, age, body mass index, diabetes, race, physical activity, and dietary factors.

They found that among all men with periodontal disease, the multivariable relative risk for pancreatic cancer compared with men with no periodontal disease was 1.64 (95% confidence interval 1.19-2.26, P=0.002). The crude incidence rate for pancreatic cancer among all men with periodontal disease was 61/100,000 person-years, compared with 25/100,000 for all men in the cohort without periodontal disease.

When they restricted the analysis only to men who never smoked, the investigators found that the relative risk of cancer of the pancreas among those with periodontal disease was 2.09 (95% CI, 1.18 -3.71; P=0.01). Among never-smokers with gum disease and tooth loss, the crude incidence rate was: 61/100,000 person-years, compared with 19/100,000 among all never-smokers with healthy gums.

The author also found that "increased severity of periodontal disease, as manifested by periodontitis with recent tooth loss, was associated with the greatest risk."

When they looked for an association between other measures of oral health (e.g., caries) and pancreatic cancer, however, they found that neither the baseline number of natural teeth, nor cumulative tooth loss during follow-up were strongly associated with increased risk for pancreatic cancer.

Dr. Michaud and colleagues noted that among the men in the study with periodontal disease, levels of C-reactive protein were 30% higher compared with men with no periodontal disease, lending credence to the idea that inflammation could play a role in carcinogenesis.

"Alternatively, periodontal disease could influence pancreatic carcinogenesis through increased generation of carcinogens, namely nitrosamines," they wrote. "Individuals with periodontal disease and poor oral hygiene have elevated levels of oral bacteria and have much higher nitrosamine levels in their oral cavity due to nitrate-reducing bacteria. Nitrosamines and gastric acidity have been hypothesized to have an important role in pancreatic cancer; numerous studies support this hypothesis."

The authors noted that their study was limited by the fact that periodontal disease was self-reported, and the incidence may have been subject to measurement error.

The study was supported by grants from the National Cancer Institute. The authors had no relevant financial disclosures.