Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study

Abstract

Objective A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study. Design We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression. Results Carriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum Fusobacteria and its genus Leptotrichia were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2 years of sample collection, reducing the likelihood of reverse causation in this prospective study. Conclusions This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.

Leptotrichia species in human infections II

“…They also found that a greater abundance of the phylum Fusobacteria was associated with decreased pancreatic cancer risk as well as its genus Leptotrichia [66]. Their finding was inconsistent with a recent cross-sectional study of eight patients, which found higher abundances of Leptotrichia and Porphyromonas in the saliva of pancreatic cancer patients compared to controls and those with other diseases, including non-cancerous pancreatic disease [18].…”

“…They were also recovered from oral plaque of guinea pigs [21] and feces of piglets [54], dental plaque from healthy individuals, plaque and saliva from patients with various types of caries, gingivitis, chronic periodontitis, and peri-implantitis [23,25–27,34,35,37,38,44,45,47,49,52,59,60,62,66–69,91,94], decayed tooth surfaces and discordant caries from intact enamel surfaces [53]. Leptotrichia species were also isolated from bronchoalveolar lavage fluid, and patients with leukocytosis, hypoxemia, and dyspnea [24].…”

“…Leptotrichia species were also isolated from bronchoalveolar lavage fluid, and patients with leukocytosis, hypoxemia, and dyspnea [24]. Further, Leptotrichia species were recovered from healthy patients with oral cancer, premalignant oral lesion [18,28,33,56,91], edentulous infants [29], human vaginal fluid of sexually active and inactive individuals [30,32], HIV-seropositive and -seronegative patients [46], pancreatic cancer patients [18,66], black pigmented stain caries patients [63], and patients with halitosis (Table 2) [42,65,81,82]. Besides, Leptotrichia species were isolated from the blood [4,5,22,74], the amniotic fluid of a patient with a wound and respiratory difficulties [4], breast milk of obese women with gestational diabetes and normal weight [36], oral samples of a patient with new-onset rheumatoid arthritis [20], oral lichen planus patients [88], and even from fermenting Lees liquor [39].…”

“…A few Leptotrichia species were related to 88 incidences of various cancers [4–7,9–11,13–15,17–19,22,28,33,40,57,60,61,66,74,80,87,91], of which 43 cases had neutropenia, sepsis, and fever [4–7,9,10,12–15,17,22,24,33,87], 14 had transplant issues [4,9,10,13,16,17,22,33], 14 mucositis [4,7,9,13–15,17,22,87], 12 various lesions (6, 11, 27, 32, 37, 44, 56 64, 99), and five pneumonia [5,9,11,24,33]. The suspected port of Leptotrichia entry included mucositis, abscesses, wound infections, gingivitis, diverticulitis, peritonitis, neutropenic sepsis, and ulcers (Table 2).…”

“…In an examination of the relationship of the oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study, the authors reported that the carriage of oral pathogens, P. gingivalis and Aggregatibacter actinomycetemcomitans , was associated with a higher risk of pancreatic cancer [66]. They also found that a greater abundance of the phylum Fusobacteria was associated with decreased pancreatic cancer risk as well as its genus Leptotrichia [66].…”