Prebiotics and the Risk of Upper Digestive Tract and Stomach Cancers: The PrebiotiCa Study.

BACKGROUND: Fiber intake may lower digestive tract cancer risk, possibly by modulating the composition of gut microbiota. However, no data are available about the role of specific fiber fractions with prebiotic activity (e.g., inulin-type fructans (ITFs), fructo-oligosaccharides (FOSs) and galactooligosaccharides (GOSs)) on the risk lower digestive tract cancers. OBJECTIVE: The objective was to assess the association between prebiotic intake and the risk of cancers of the upper digestive tract and stomach. DESIGN: Within the PrebiotiCa study, data were derived from a network of Italian case-control studies conducted between 1992 and 2009. Participants' usual diet was assessed using a food frequency questionnaire. ITFs, and selected FOSs (nystose, kestose, and 1F-ß-fructofuranosylnystose) and GOSs (raffinose and stachyose) were quantified in several food products via laboratory analyses. Participants' prebiotic intake was calculated by multiplying food frequency questionnaire intake by the prebiotic content of each food item. PARTICIPANTS/SETTING: Cases were patients admitted to major hospitals with incident histologically confirmed cancers; there were 946 cases of cancer of the oral cavity/pharynx, 198 of the nasopharynx, 304 of the esophagus, 230 of the stomach. More than 4,000 patients admitted to the same hospitals for acute nonneoplastic and not diet-related conditions were selected as control subjects. MAIN OUTCOME MEASURES: The outcomes were oral and pharyngeal, nasopharyngeal, esophageal, and stomach cancers. STATISTICAL ANALYSES PERFORMED: The odds ratios and corresponding 95% CIs of the various cancers were derived using logistic regression models adjusted for major confounders and energy intake. RESULTS: No association was observed between intake of prebiotics and risk of cancers of the oral cavity and pharynx, nasopharynx, and esophagus. High raffinose intake reduced stomach cancer risk (odds ratio for the third vs the first tertile 0.6, 95% CI 0.3 to 0.9); no other prebiotic was associated with stomach cancer. CONCLUSIONS: The current study does not support a major role of prebiotic fibers on selected upper digestive tract cancers. The association between high raffinose intake and reduced stomach cancer risk needs further investigation.

Alternative non-oral nutrition in a rat model: a novel modified gastrostomy technique.

The gastrostomy technique is essential for esophageal reconstruction using a scaffold. To date, there are no established methods to supply nutrients through a gastrostomy tube in rats. The purpose of this study was to analyze the feasibility of a newly modified gastrostomy technique for non-oral nutrition in an adult rat model. We modified the gastrostomy technique for adult rats in a few different ways. (1) The external opening for food injection was made at the midpoint between the ears to prevent damage due to self-harm behaviour. (2) An imbedded subcutaneous tunnel was created between the internal and external openings of the gastrostomy. We compared the efficacy and safety between groups with a T-tube for biliary drainage (TT group, n=14) and a conventional silicone Foley catheter (FC group, n=7) as optimal gastrostomy tubes for in a rat model. We also evaluated the feasibility of the heparin cap connector at the end of gastrostomy tube to control food supply in the TT group (with a cap, n=7; without a cap, n=7). No mortality was observed in the TT group with a cap, whereas most rats in the FC group died within 2 weeks after the procedure. Weight loss decreased significantly in the TT group with a cap compared with all the other groups. The appearance and attitude scores were significantly better in the TT group with a cap. In addition, histologic analysis showed that the TT group a cap showed a marked decrease over time in tissue fibrosis and macrophages compared with the other experimental groups. Therefore, gastrostomy using a silicone T-tube plugged with a cap proved to be a stable and effective option for non-oral feeding in an adult rat model.

Cancer susceptibility of beta HPV49 E6 and E7 transgenic mice to 4-nitroquinoline 1-oxide treatment correlates with mutational signatures of tobacco exposure.

We have previously showed that a transgenic (Tg) mouse model with cytokeratin 14 promoter (K14)-driven expression of E6 and E7 from beta-3 HPV49 in the basal layer of the epidermis and of the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7 Tg mice) are highly susceptible to upper digestive tract carcinogenesis upon exposure to 4-nitroquinoline 1-oxide (4NQO). Using whole-exome sequencing, we show that in K14 HPV49 E6/E7 Tg mice, development of 4NQO-induced cancers tightly correlates with the accumulation of somatic mutations in cancer-related genes. The mutational signature in 4NQO-treated mice was similar to the signature observed in humans exposed to tobacco smoking and tobacco chewing. Similar results were obtained with K14 Tg animals expressing mucosal high-risk HPV16 E6 and E7 oncogenes. Thus, beta-3 HPV49 share some functional similarities with HPV16 in Tg animals.

Different frequencies of Porphyromonas gingivalis infection in cancers of the upper digestive tract.

The high incidence rate of multiple carcinomas in the upper digestive tract is often explained in terms of involvement of the same underlying risk factors. It has been reported that the oral bacterium Streptococcus anginosus is associated with esophageal, gastric, and pharyngeal cancers. We previously reported occurrence of Porphyromonas gingivalis (P. gingivalis) DNA in esophagus cancer. In this study, the presence of P. gingivalis in specimens of various types of cancer from the upper digestive tract was investigated. Here we report that P. gingivalis was preferentially and frequently present in specimens of esophageal cancer as well as in those from dysplasia of the esophagus but rarely in matched noncancerous portions and are quite low or absent in cancers from the cardia or stomach. Therefore, it led us to propose that, the microorganism does not survive in conditions of high acidity. We then investigate the pH dependence of survival of P. gingivalis as well as the acid tolerance of it. We found that, exposure to acidic buffers of a wide range of pH values led to a decline in colony forming units of P. gingivalis, thus, providing a possible explanation for variations in frequencies of P. gingivalis infection in this study.