External Airborne-agent Exposure Increase Risk of Digestive Tract Cancer.
ABSTRACT: Previous studies have suggested that in addition to respiratory system cancers, exposure to external airborne agents (EAAs) may also affect the risk of digestive tract cancer. However, previous epidemiological studies have been limited. To clarify this relationship, we conducted a Workers' Korea National Health Insurance Service cohort study. The EAA exposure group comprised participants who had ever visited a hospital as an inpatient for 'lung diseases due to external agents'. The reference population comprised men from the general working population. The EAA exposure group and reference group included a total of 98,666 and 79,959,286 person-years, respectively. Age-adjusted standardized incident rates (SIRs) with 95% confidence intervals (95%CI) were calculated for each 5-year age stratum. The SIR (95% CI) of EAA exposure was 1.30 (1.19-1.38) for all digestive tract cancers. The highest risk associated with EAA exposure was observed for oral cancer, followed by esophageal and stomach cancers [SIRs (95%CI): 3.96 (3.02-4.78), 3.47(2.60-4.25), and 1.34(1.17-1.47), respectively.] These statistically significant associations did not be attenuated in a subgroup analysis using logistic regression adjusted for age, smoking and alcohol consumption. Our findings suggest that EAA exposure should address risk reduction of both digestive tract and respiratory system cancers.
Project description:Insect gut microbes have been shown to provide nutrients such as essential amino acids (EAAs) to their hosts. How this symbiotic nutrient provisioning tracks with the host's demand is not well understood. In this study, we investigated microbial essential amino acid (EAA) provisioning in omnivorous American cockroaches (Periplaneta americana), fed low-quality (LQD) and comparatively higher-quality dog food (DF) diets using carbon stable isotope ratios of EAAs (? (13)CEAA). We assessed non-dietary EAA input, quantified as isotopic offsets (?(13)C) between cockroach (? (13)CCockroach EAA) and dietary (? (13)CDietary EAA) EAAs, and subsequently determined biosynthetic origins of non-dietary EAAs in cockroaches using (13)C-fingerprinting with dietary and representative bacterial and fungal ? (13)CEAA. Investigation of biosynthetic origins of de novo non-dietary EAAs indicated bacterial origins of EAA in cockroach appendage samples, and a mixture of fungal and bacterial EAA origins in gut filtrate samples for both LQD and DF-fed groups. We attribute the bacteria-derived EAAs in cockroach appendages to provisioning by the fat body residing obligate endosymbiont, Blattabacterium and gut-residing bacteria. The mixed signatures of gut filtrate samples are attributed to the presence of unassimilated dietary, as well as gut microbial (bacterial and fungal) EAAs. This study highlights the potential impacts of dietary quality on symbiotic EAA provisioning and the need for further studies investigating the interplay between host EAA demands, host dietary quality and symbiotic EAA provisioning in response to dietary sufficiency or deficiency.
Project description:Background:We examined the role of the insulinemic potential of diet and lifestyle in the development of cancers of the digestive system, using two plasma C-peptide-based indices: the empirical dietary index for hyperinsulinemia (EDIH) and empirical lifestyle index for hyperinsulinemia (ELIH). Methods:We used Cox regression to analyze data on 45 816 men (Health Professionals Follow-up Study, 1986-2012) and 74 191 women (Nurses' Health Study, 1984-2012) to examine associations between EDIH and ELIH scores and digestive system cancers. We computed the diet-only score (EDIH) from food-frequency questionnaires administered every 4?years. The lifestyle score (ELIH) included diet, body mass index, and physical activity. Outcomes included incident cancer of the digestive system (mouth, throat, esophagus, stomach, small intestine, and colorectum) and its accessory organs (pancreas, gallbladder, and liver). P values were two-sided. Results:We found direct associations between higher insulinemic potential of diet or lifestyle and risk of developing digestive system cancers in both men and women. The pooled multivariable hazard ratios (HRs) for participants comparing the highest to lowest EDIH quintile were: HR = 1.27, 95% confidence interval (CI) = 1.15 to 1.40, P trend?<?.001 for digestive system cancers; HR = 1.30, 95% CI = 1.17 to 1.45, P trend < .001 for digestive tract cancers (excluding accessory organs); and HR = 1.15, 95% CI = 0.93 to 1.41, P trend = .48 for digestive accessory organ cancers. The same associations were stronger with the lifestyle score: HR = 1.47, 95% CI = 1.23 to 1.76, P trend < .001 for digestive system cancers; HR = 1.49, 95% CI = 1.14 to 1.95, P trend = .001 for digestive tract cancers; and HR = 1.43, 95% CI = 1.17 to 1.73, P trend < .001 for digestive accessory organ cancers. Conclusions:The findings suggest that interventions to reduce the insulinemic potential of diet and lifestyle may be a means of preventing digestive system cancer.
Project description:Dietary sources of essential amino acids (EAAs) are used for growth, somatic maintenance and reproduction. Eusocial insect workers such as honeybees are sterile, and unlike other animals, their nutritional needs should be largely dictated by somatic demands that arise from their role within the colony. Here, we investigated the extent to which the dietary requirements of adult worker honeybees for EAAs and carbohydrates are affected by behavioural caste using the Geometric Framework for nutrition. The nutritional optimum, or intake target (IT), was determined by confining cohorts of 20 young bees or foragers to liquid diets composed of specific proportions of EAAs and sucrose. The IT of young, queenless bees shifted from a proportion of EAAs-to-carbohydrates (EAA:C) of 1:50 towards 1:75 over a 2-week period, accompanied by a reduced lifespan on diets high in EAAs. Foragers required a diet high in carbohydrates (1:250) and also had low survival on diets high in EAA. Workers exposed to queen mandibular pheromone lived longer on diets high in EAA, even when those diets contained 5× their dietary requirements. Our data show that worker honeybees prioritize their intake of carbohydrates over dietary EAAs, even when overeating EAAs to obtain sufficient carbohydrates results in a shorter lifespan. Thus, our data demonstrate that even when young bees are not nursing brood and foragers are not flying, their nutritional needs shift towards a diet largely composed of carbohydrates when they make the transition from within-hive duties to foraging.
Project description:Insects are unable to synthesize essential amino acids (EAAs) de novo, thus rely on dietary or symbiotic sources for them. Wood is a poor resource of nitrogen in general, and EAAs in particular. In this study, we investigated whether gut microbiota of the Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), a cerambycid that feeds in the heartwood of healthy host trees, serve as sources of EAAs to their host under different dietary conditions. ?(13)C-stable isotope analyses revealed significant ?(13)C-enrichment (3.4 ± 0.1‰; mean ± SEM) across five EAAs in wood-fed larvae relative to their woody diet. ?(13)C values for the consumers greater than 1‰ indicate significant contributions from non-dietary EAA sources (symbionts in this case). In contrast, ?(13)C-enrichment of artificial diet-fed larvae (controls) relative to their food source was markedly less (1.7 ± 0.1‰) than was observed in wood-fed larvae, yet still exceeded the threshold of 1‰. A predictive model based on ?(13)CEAA signatures of five EAAs from representative bacterial, fungal, and plant samples identified symbiotic bacteria and fungi as the likely supplementary sources of EAA in wood-fed larvae. Using the same model, but with an artificial diet as the dietary source, we identified minor supplementary bacterial sources of EAA in artificial diet-fed larvae. This study highlights how microbes associated with A. glabripennis can serve as a source of EAAs when fed on nutrient-limited diets, potentially circumventing the dietary limitations of feeding on woody substrates.
Project description:BACKGROUND:The development of effective nutritional strategies in support of muscle growth for patients with chronic obstructive pulmonary disease (COPD) remains challenging. Dietary essential amino acids (EAAs) are the main driver of postprandial net protein anabolism. In agreement, EAA supplements in healthy older adults are more effective than supplements with the composition of complete proteins. In patients with COPD it is still unknown whether complete protein supplements can be substituted with only EAAs, and whether they are as effective as in healthy older adults. METHODS:According to a double-blind randomized crossover design, we examined in 23 patients with moderate to very severe COPD (age: 65±2 years, FEV1: 40±2% of predicted) and 19 healthy age-matched subjects (age: 64±2 years), whether a free EAA mixture with a high proportion (40%) of leucine (EAA mixture) stimulated whole body net protein gain more than a similar mixture of balanced free EAAs and non-EAAs as present in whey protein (TAA mixture). Whole body net protein gain and splanchnic extraction of phenylalanine (PHE) were assessed by continuous IV infusion of L-[ring-2H5]-PHE and L-[ring-2H2]-tyrosine, and enteral intake of L-[15N]-PHE (added to the mixtures). RESULTS:Besides an excellent positive linear relationship between PHE intake and net protein gain in both groups (r=0.84-0.91, P<0.001), net protein gain was 42% higher in healthy controls and 49% higher in COPD patients after intake of the EAA mixture compared to the TAA mixture (P<0.0001). These findings could not be attributed to the high LEU content, as in both groups net protein gain per gram EAA intake was lower for the EAA mixture (P<0.0001). Net protein gain was higher in COPD patients for both mixtures due to a 40% lower splanchnic extraction (P<0.0001), but was similarly related to dietary PHE (i.e. EAA) plasma appearance. CONCLUSIONS:In COPD patients, similarly to healthy older adults, free EAA supplements stimulate whole body protein anabolism more than free amino acid supplements with the composition of complete proteins. Therefore, free EAA supplements may aid in the prevention and treatment of muscle wasting in this patient population.
Project description:BACKGROUND:Since the number of cancer survivors is increasing, it is imperative that we better understand the long-term consequences of these survivors. We assessed the risk of developing a second primary malignant neoplasm (SPMN) after an index potentially-HPV-associated cancers (P-HPV-AC). METHODS:We constructed a population-based cohort of patients with P-HPV-AC using Surveillance, Epidemiology, and End Results registry data (2000-2015). We limited patients to those with invasive P-HPV-AC [cervical, vagina, vulva, penile, anal, and oropharynx] based on the International Classification of Diseases for Oncology, 3rd edition. Excess SPMN risks were calculated based on standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR). RESULTS:A total of 105,644 patients with an index P-HPV-AC were identified, and 7.8 % developed a SPMN. In all P-HPV-AC patients, the overall SIR was 1.73 (95 % CI: 1.69-1.77) and EAR of 70.72 per 10,000 PYR. All index P-HPV-AC sites showed statistically significant increases in the risk of SPMN, except for anal cancer among men, compared with the general population. The greatest increase in risk of SPMN was observed among patients diagnosed with an index P-HPV-oropharyngeal cancer (SIR?=?1.83; 95 % CI, 1.70-1.82 and SIR?=?2.29; 95 % CI, 2.12-2.47 for men and women, respectively). Men developed SPMN mostly in aero-digestive tract whiles women developed SPMN both in aero-digestive tract and other HPV-associated cancer sites. CONCLUSIONS:P-HPV-AC survivors experienced excess risk of SPMN. These findings have the potential to affect future surveillance practices and improve preventive healthcare for survivors of P-HPV-ACs.
Project description:Gut-associated microbes of insects are postulated to provide a variety of nutritional functions including provisioning essential amino acids (EAAs). Demonstrations of EAA provisioning in insect-gut microbial systems, nonetheless, are scant. In this study, we investigated whether the eastern subterranean termite Reticulitermes flavipes sourced EAAs from its gut-associated microbiota. ? (13)CEAA data from termite carcass, termite gut filtrate and dietary (wood) samples were determined following (13)C stable isotope analysis. Termite carcass samples (-27.0 ± 0.4‰, mean ± s.e.) were significantly different from termite gut filtrate samples (-27.53 ± 0.5‰), but not the wood diet (-26.0 ± 0.5‰) (F (2,64) = 6, P < 0.0052). ? (13)CEAA-offsets between termite samples and diet suggested possible non-dietary EAA input. Predictive modeling identified gut-associated bacteria and fungi, respectively as potential major and minor sources of EAAs in both termite carcass and gut filtrate samples, based on ? (13)CEAA data of four and three EAAs from representative bacteria, fungi and plant data. The wood diet, however, was classified as fungal rather than plant in origin by the model. This is attributed to fungal infestation of the wood diet in the termite colony. This lowers the confidence with which gut microbes (bacteria and fungi) can be attributed with being the source of EAA input to the termite host. Despite this limitation, this study provides tentative data in support of hypothesized EAA provisioning by gut microbes, and also a baseline/framework upon which further work can be carried out to definitively verify this function.
Project description:BACKGROUND: The Xeroderma pigmento-sum group D gene (XPD) plays a key role in nucleotide excision repair. Single nucleotide polymorphisms (SNP) located in its functional region may alter DNA repair capacity phenotype and cancer risk. Many studies have demonstrated that XPD polymorphisms are significantly associated with digestive tract cancers risk, but the results are inconsistent. We conducted a comprehensive meta-analysis to assess the association between XPD Lys751Gln polymorphism and digestive tract cancers risk. The digestive tract cancers that our study referred to, includes oral cancer, esophageal cancer, gastric cancer and colorectal cancer. METHODS: We searched PubMed and EmBase up to December 31, 2012 to identify eligible studies. A total of 37 case-control studies including 9027 cases and 16072 controls were involved in this meta-analysis. Statistical analyses were performed with Stata software (version 11.0, USA). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: The results showed that XPD Lys751Gln polymorphism was associated with the increased risk of digestive tract cancers (homozygote comparison (GlnGln vs. LysLys): OR = 1.12, 95% CI = 1.01-1.24, P = 0.029, P heterogeneity = 0.133). We found no statistical evidence for a significantly increased digestive tract cancers risk in the other genetic models. In the subgroup analysis, we also found the homozygote comparison increased the susceptibility of Asian population (OR = 1.28, 95% CI = 1.01-1.63, P = 0.045, P heterogeneity = 0.287). Stratified by cancer type and source of control, no significantly increased cancer risk was found in these subgroups. Additionally, risk estimates from hospital-based studies and esophageal studies were heterogeneous. CONCLUSIONS: Our meta-analysis suggested that the XPD 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations.
Project description:Background:Indians have a poor protein intake in terms of quantity as well as quality because of their predominantly cereal-based diet. However, there is limited information on circulatory amino acid levels in healthy Indians. Herein, we evaluated the acute effect of a protein supplement on the plasma levels of essential amino acids (EAAs) in healthy Indian adults, using targeted EAA analysis. Methods:In this double-blind, randomized, crossover study, 20 healthy Indian adults were randomized to receive the test protein supplement (treatment arm, n?=?10) or placebo (control arm, n?=?10) with milk, after overnight fasting. After 7 days, the participants returned for the crossover treatment. Blood samples were collected at baseline and at 60 and 120?min after protein/placebo consumption. Plasma EAA levels were estimated using liquid chromatography-tandem mass spectrometry. Repeated measures ANOVA was performed to assess the effect of treatment on EAA levels. P values?<?0.05 were considered statistically significant. Results:At baseline, mean plasma levels did not differ significantly between the two arms for any of the EAAs. In the treatment arm, the mean levels of all EAAs increased significantly from baseline to 60?min (P < 0.01), with no significant change from 60 to 120?min. There was no significant change in amino acid levels in the control arm. The magnitude as well as percentage of increase from baseline to 60?min was significantly greater in the treatment arm than in the control arm for all EAAs. Conclusion:Compared to placebo, protein supplement increased circulatory amino acid levels in healthy Indians. The observed increase in EAA levels and its role in conjunction with exercise in both healthy and diseased states need to be further evaluated. This is the first dataset exploring targeted EAA profiles and the effect of a protein supplement among healthy Indians. The clinical trial is registered with CTRI/2018/12/016777.
Project description:IMPORTANCE:Accumulating evidence indicates that common carcinogenic pathways may underlie digestive system cancers. Physical activity may influence these pathways. Yet, to our knowledge, no previous study has evaluated the role of physical activity in overall digestive system cancer risk. OBJECTIVE:To examine the association between physical activity and digestive system cancer risk, accounting for amount, type (aerobic vs resistance), and intensity of physical activity. DESIGN, SETTING, AND PARTICIPANTS:A prospective cohort study followed 43 479 men from the Health Professionals Follow-up Study from 1986 to 2012. At enrollment, the eligible participants were 40 years or older, were free of cancer, and reported physical activity. Follow-up rates exceeded 90% in each 2-year cycle. EXPOSURES:The amount of total physical activity expressed in metabolic equivalent of task (MET)-hours/week. MAIN OUTCOMES AND MEASURES:Incident cancer of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver). RESULTS:Over 686?924 person-years, we documented 1370 incident digestive system cancers. Higher levels of physical activity were associated with lower digestive system cancer risk (hazard ratio [HR], 0.74 for ?63.0 vs ?8.9 MET-hours/week; 95% CI, 0.59-0.93; P value for trend?=?.003). The inverse association was more evident with digestive tract cancers (HR, 0.66 for ?63.0 vs ?8.9 MET-hours/week; 95% CI, 0.51-0.87) than with digestive accessary organ cancers. Aerobic exercise was particularly beneficial against digestive system cancers, with the optimal benefit observed at approximately 30 MET-hours/week (HR, 0.68; 95% CI, 0.56-0.83; P value for nonlinearity?=?.02). Moreover, as long as the same level of MET-hour score was achieved from aerobic exercise, the magnitude of risk reduction was similar regardless of intensity of aerobic exercise. CONCLUSIONS AND RELEVANCE:Physical activity, as indicated by MET-hours/week, was inversely associated with the risk of digestive system cancers, particularly digestive tract cancers, in men. The optimal benefit was observed through aerobic exercise of any intensity at the equivalent of energy expenditure of approximately 10 hours/week of walking at average pace. Future studies are warranted to confirm our findings and to translate them into clinical and public health recommendation.