October 14, 2011 — A pair of bacteria in the saliva are associated with pancreatic cancer and chronic pancreatitis, according to a study published online (http://gut.bmj.com/content/early/2011/09/23/gutjnl-2011-300784.abstract) October 12 in Gut. Although a press release from the journal attributes the suggestion that this finding "opens up the possibility of curbing the progress of one of the most difficult cancers to treat, by altering the balance of bacteria," to the researchers, they were, in fact, much more circumspect.
According to lead author James J. Farrell, MD, MD, from the division of digestive diseases at the UCLA David Geffen School of Medicine in Los Angeles, California, the key finding is that the study provides proof of principle that differences in the microbiota in saliva can serve as noninvasive biomarkers for diagnosing and differentiating pancreatic cancer and chronic pancreatitis.
Dr. Farrell told Medscape Medical News that "we need to validate the panel of salivary biomarkers, both bacterial and transcriptomic, in a larger prospective study, enrolling patients suspected of having pancreatic disease and cancer and following them over time. This is currently underway. The big unanswered question is: Are these bacteria causing or the result of the cancer? Most data from previous studies and studies in other disease suggest that the bacteria are directly or indirectly contributing to the development of pancreatic disease, likely through inflammation."
The researchers used the human oral microbe identification microarray (HOMIM) to examine salivary microbiota in 10 patients with resectable pancreatic cancer and 10 matched healthy control subjects. They then used real-time quantitative polymerase chain reaction (qPCR) to identify the bacterial species or clusters that were notably different in the saliva of patients with pancreatic cancer and that of control subjects. Finally, they validated the candidate marker bacteria with qPCR on saliva from 28 patients with pancreatic cancer, 27 with chronic pancreatitis, and 28 control subjects.
The initial analysis identified 31 bacterial species or clusters that were higher in the saliva of patients with pancreatic cancer than in control subjects, and 25 that were lower. Two of the 6 candidate bacteria validated in the independent samples were present at significantly different levels in the patient and control groups: Neisseria elongata and Streptococcus mitis. Furthermore, 2 bacteria (Granulicatella adjacens and S mitis) were present at different levels in patients with chronic pancreatitis and in control subjects.
Causative Rather Than Reactive?
Dr. Farrell's group then combined N elongata and S mitis and determined that the pair distinguished patients with pancreatic cancer from control subjects with 96.4% sensitivity and 82.1% specificity.
The authors write that "whether a variation in bacterial abundance is a causative factor for cancer carcinogenesis or a derivational reflection of cancer onset due to the change of oral niches needs to be further explored in longitudinal.... Taken together [with the association between chronic pancreatitis and pancreatic cancer], these data suggest that the association between variations in oral microbiota and pancreatic disease may likely be causative rather than reactive."
The authors note that they were unable to test for possible changes in oral bacteria after pancreatic cancer resection.
They also note that "none of the bacterial biomarkers validated in this study was significantly altered in the microflora profile of lung cancer."
Limitations in Study Design
However, Dominique Michaud, ScD, associate professor of community health at Brown University in Providence, Rhode Island, who reviewed the paper for Medscape Medical News, is more cautious. Dr. Michaud, whose research centers on causes of pancreatic and brain cancers, and who has studied periodontal disease and pancreatic cancer (J Natl Cancer Inst. 2007;99:171-175), said that although "this is an interesting preliminary study, it is far from conclusive. There are many limitations to the study design, including small numbers and lack of other diseased control subjects. These findings need to be replicated and cannot provide any information on causality. It is very possible that any immunocompromised patient would have the same profile of saliva bacteria, which means this would test would not be a useful clinical screening tool."
Dr. Farrell told Medscape Medical News that his group is currently enrolling patients in a nested, case–control study to see how these biomarkers behave in a large general population to detect pancreatic disease, and that efforts are underway to convert the HOMIM, which is currently only a research tool, for patient and clinic-based salivary diagnostics.
Dr. Farrell and Dr. Michaud have disclosed no relevant financial relationships. Coauthor David T.W. Wong, from the David Geffen School of Medicine, reports ownership of intellectual property related to the saliva diagnostics field.