Risk Of Gastrointestinal Tract Cancers Research Articles

VEGF-2578C/A, -460T/C Polymorphisms and Gastrointestinal Tract Cancer Risk: An Updated Meta-Analysis.

Functional polymorphisms in the vascular endothelial growth factor (VEGF) alter the susceptibility toward different gastrointestinal tract (GIT) cancers. In this study, we explored the association of VEGF-2578C/A and VEGF-460T/C polymorphisms with esophageal cancer (EC) risk. In total, 330 patients with EC and 330 controls for VEGF-2578C/A polymorphism and 316 patients with EC and 316 controls for VEGF-460T/C polymorphism were genotyped. AA genotype (p = 0.01) and A allele (p = 0.02) of VEGF-2578C/A and CC genotype (p = 0.04) and C allele (p = 0.04) of VEGF-460T/C polymorphism were significantly associated with an increased risk of EC. VEGF-2578C/A and VEGF-460T/C polymorphisms have been studied in different GIT cancers, but results are inconclusive. Therefore, we performed a meta-analysis to assess the association of these polymorphisms with the risk of GIT cancers. The PubMed, ScienceDirect, and Google Scholar databases were used to search the articles. Twenty-one studies on VEGF-2578C/A and 20 studies on VEGF-460T/C polymorphism were included in this meta-analysis. VEGF-2578C/A polymorphism was associated with the decreased risk of GIT cancer in the overall population under the overdominant model (p = 0.009). A significant association of VEGF-2578C/A polymorphism with GIT cancer risk has been observed in the middle easterners, Caucasians, and Asians under different genetic models. VEGF-460T/C polymorphism was significantly associated with an increased risk of GIT cancers in Caucasians. Stratification of the data on the basis of cancer type showed a significant association of VEGF-2578C/A polymorphism with the risk of gallbladder cancer, whereas VEGF-460T/C polymorphism was associated with the risk of hepatocellular cancer, gastric cancer, and colorectal cancer. Our meta-analysis suggested that VEGF-2578C/A and VEGF-460T/C polymorphisms were associated with GIT cancer risk.

Association of VEGF-116G/A Promoter Polymorphism with Esophageal Cancer Risk: A Case-Control study and an Updated Meta-Analysis on Gastrointestinal Tract Cancers.

The present study aimed to investigate the potential association of VEGF-116G/A promoter polymorphism with esophageal cancer risk in North-West Indians and to perform a comprehensive meta-analysis of VEGF-116G/A polymorphism in Gastrointestinal Tract (GIT) cancers. A total of 679 DNA samples (333 esophageal cancer patients and 346 healthy controls) were genotyped for VEGF-116G/A polymorphism using Sanger sequencing. In silico analysis was carried out to predict the impact of VEGF-116G/A polymorphism on transcription factor binding sites. Ten studies including 2157 patients and 2307 controls on different GIT cancers were included in the meta-analysis. Results: The AA genotype and A allele of VEGF -116G/A polymorphism was significantly associated with an increased risk of esophageal cancer. In silico analysis predicted that A allele of VEGF-116G/A polymorphism created new binding sites for STAT4, c-Ets-1 and Elk-1 transcription factors. The meta-analysis results showed that VEGF-116G/A polymorphism was associated with an increased risk of GIT cancer under the recessive and AA vs GG genetic model in the overall population. Stratification of the studies by ethnicity revealed an increased risk of GIT cancers in Asians under allele contrast, recessive, AA vs GG and AA vs AG model. Analysis based on cancer type revealed an increased risk of esophageal cancer under allele contrast, recessive, AA vs GG and AA vs AG comparison model and increased risk of oral cancer was observed under the allele contrast model and dominant model. VEGF-116G/A polymorphism was associated with esophageal cancer risk in North- West Indians. The findings of the present meta-analysis showed a significant association of VEGF-116G/A polymorphism with GIT cancer risk.

Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies.

There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract. A series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use. There was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively). In this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

Rare variants confer shared susceptibility to gastrointestinal tract cancer risk.

Cancers arising within the gastrointestinal tract are complex disorders involving genetic events that cause the conversion of normal tissue to premalignant lesions and malignancy. Shared genetic features are reported in epithelial-based gastrointestinal cancers which indicate common susceptibility among this group of malignancies. In addition, the contribution of rare variants may constitute parts of genetic susceptibility. A cross-cancer analysis of 38,171 shared rare genetic variants from genome-wide association assays was conducted, which included data from 3,194 cases and 1,455 controls across three cancer sites (esophageal, gastric and colorectal). The SNP-level association was performed by multivariate logistic regression analyses for single cancer, followed by association analysis for SubSETs (ASSET) to adjust the bias of overlapping controls. Gene-level analyses were conducted by SKAT-O, with multiple comparison adjustments by false discovery rate (FDR). Based on the significant genes indicated by SKATO analysis, pathways analysis was conducted using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Meta-analysis in three gastrointestinal (GI) cancers identified 13 novel susceptibility loci that reached genome-wide significance (P ASSET< 5×10-8). SKAT-O analysis revealed EXOC6, LRP5L and MIR1263/LINC01324 to be significant genes shared by GI cancers (P adj<0.05, P FDR<0.05). Furthermore, GO pathway analysis identified significant enrichment of synaptic transmission and neuron development pathways shared by all three cancer types. Rare variants and the corresponding genes potentially contribute to shared susceptibility in different GI cancer types. The discovery of these novel variants and genes offers new insights for the carcinogenic mechanisms and missing heritability of GI cancers.

Levels of evidence for the association between different food groups/items consumption and the risk of various cancer sites: an umbrella review

This study aimed to determine the level of evidence on the association between food groups/items consumption and the risk of different cancer sites from the meta-analyses/pooled analyses of observational studies. A systematic search was executed in Scopus, PubMed/MEDLINE, and Web of Science. The criteria from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Expert Report were adopted for evidence grading. In summary, there was convincing evidence for the association between fibre intake and decreased risk of colon and breast cancer. Also, consumption of dairy products, milk, fruits, and fibre was associated with a probable decreased risk of breast cancer. Consumption of whole grains, dairy products, milk, fruits, vegetables, and fibre had a probable inverse association with the incidence risk of gastrointestinal tract cancers. More qualified studies are needed to find reliable findings on the association between various food groups/items consumption and the risk of different cancer sites.

Site-Specific Hypermethylation of SST 1stExon as a Biomarker for Predicting the Risk of Gastrointestinal Tract Cancers.

Background DNA methylation is an important epigenetic modification in tumorigenesis, and similar epigenetic regulation mechanisms have been found in the gastrointestinal tract (GIT) cancers. Somatostatin (SST) has been confirmed to be expressed throughout the GIT. This study aimed to simultaneously explore the relationships between the SST methylation and the risks of three GIT cancers (esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC)) and to evaluate its diagnostic value. Methods Differentially methylated regions (DMRs) of the SST gene, including TSS200, 1stExon, and the gene body, were identified in GIT cancers by The Cancer Genome Atlas (TCGA) database analysis. Further analyses were conducted in tissue samples of EC (n = 50), GC (n = 99), and CRC (n = 80). The SST methylation was detected by bisulfite-sequencing PCR (BSP), and the SST expression was detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Results In GIT cancers, DMR-related CpG islands were mainly located in the 1stExon. The methylation status of the SST 1stExon in the tumor tissues was significantly higher than that in the adjacent noncancerous tissues, and the methylation rates of the specific CpG sites were correlated with clinical phenotypes. The average methylation rate (AMR) of the SST 1stExon was negatively correlated with the SST gene expression in GC and CRC (both P < 0.001). For the diagnosis of GIT cancers, the combined detection of methylation at CpG sites +18 and +129 showed the highest area under the curve (AUC 0.698), with a sensitivity of 59.3% and a specificity of 72.8%. Conclusions The site-specific hypermethylation of the SST 1stExon increases the risk of GIT cancers and might be a potential predictive marker for pan-GIT cancers.

Unrestrained eating behavior and risk of digestive system cancers: a prospective cohort study

Unrestrained eating behavior, as a potential proxy for diet frequency, timing, and caloric intake, has been questioned as a plausible risk factor for digestive system cancers, but epidemiological evidence remains sparse. We investigated prospectively the associations between unrestrained eating behavior and digestive system cancer risk. Participants in the Nurses' Health Study who were free of cancer and reported dietary information in 1994 were followed for ≤18 y. Cox models were used to estimate HRs and 95% CIs for unrestrained eating (eating anything at any time, no concern with figure change, or both) and risk of digestive system cancers. During follow-up, 2064 digestive system cancer cases were documented among 70,450 eligible participants in analyses of eating anything at any time, In total, 2081 digestive system cancer cases were documented among 72,468 eligible participants in analyses of no concern with figure change. In fully adjusted analyses, women with the behavior of eating anything at any time had a higher risk of overall digestive system cancer (HR: 1.22; 95% CI: 1.10, 1.35), overall gastrointestinal tract cancer ((HR: 1.33; 95% CI: 1.18, 1.50), buccal cavity and pharynx cancer (HR: 1.50; 95% CI: 1.02, 2.21), esophageal cancer (HR: 1.62; 95% CI: 1.01, 2.62), small intestine cancer (HR: 1.92; 95% CI: 1.02,3. 59), and colorectal cancer (HR: 1.20; 95% CI: 1.04, 1.38), and a non-statistically significant increased risk of stomach cancer (HR: 1.54; 95% CI: 0.96,2.48), compared with women without this behavior. No statistically significant association was observed for pancreatic cancer and liver and gallbladder cancer. The combined effect of eating anything at any time and having no concern with figure change was associated with a significantly increased risk of overall digestive system cancer (HR: 1.27; 95% CI: 1.10, 1.46), overall gastrointestinal tract cancer (HR: 1.45; 95% CI: 1.23, 1.71), and colorectal cancer (HR: 1.34; 95% CI: 1.11, 1.63), compared with women exhibiting the opposite. Unrestrained eating behavior was independently associated with increased risk of gastrointestinal tract cancers. The potential importance of unrestrained eating behavior modification in preventing gastrointestinal tract cancers should be noted.

Spicy food consumption and risk of gastrointestinal-tract cancers: findings from the China Kadoorie Biobank.

BackgroundPrevious case–control studies have reported positive associations of spicy food consumption with risks of certain gastrointestinal-tract (GI) cancers. However, there is no prospective evidence on such associations, particularly from China, where there are high incidence rates of GI cancers and spicy food is widely consumed.MethodsThe prospective China Kadoorie Biobank study recruited >512 000 adults aged 30–79 years from 10 areas in China during 2004–2008; 2350 oesophageal, 3350 stomach and 3061 colorectal incident cancer cases were recorded by 1 January 2017, after a median of 10.1 years of follow-up. Cox regression yielded adjusted hazard ratios (HRs) for each cancer associated with spicy food intake.ResultsOverall, 30% of participants reported daily spicy food consumption at baseline. Spicy food consumption was inversely associated with oesophageal cancer risk, with adjusted HRs of 1.00, 0.88, 0.76, 0.84 and 0.81 for those who never/rarely consumed (reference) and consumed monthly, 1–2 days/week, 3–5 days/week and 6–7 days/week, respectively (ptrend < 0.002). The association remained similar after excluding the first 3 years of follow-up but appeared stronger in participants who did not smoke or drink alcohol regularly (ptrend < 0.0001). The corresponding HRs for stomach cancer were 1.00, 0.97, 0.95, 0.92 and 0.89 (ptrend = 0.04), with the association disappearing after excluding the first 3 years of follow-up. For colorectal cancer, the HRs were 1.00, 1.00, 0.95, 0.87 and 0.90, respectively (ptrend = 0.04) and the inverse association appeared to be restricted to rectal rather than colon cancer (pheterogeneity = 0.004). The types and strength of spice used showed little additional effects on these associations.ConclusionIn Chinese adults, higher spicy food consumption was associated with lower risks of certain GI cancers, particularly among individuals who never smoked or drank alcohol regularly.

Across-Site Differences in the Mechanism of Alcohol-Induced Digestive Tract Carcinogenesis: An Evaluation by Mediation Analysis.

A genetic variant on aldehyde dehydrogenase 2 (ALDH2 rs671, Glu504Lys) contributes to carcinogenesis after alcohol consumption. Somewhat conversely, the ALDH2 Lys allele also confers a protective effect against alcohol-induced carcinogenesis by decreasing alcohol consumption due to acetaldehyde-related adverse effects. Here, we applied a mediation analysis to five case-control studies for head and neck, esophageal, stomach, small intestine, and colorectal cancers, with 4,099 cases and 6,065 controls, and explored the potentially heterogeneous impact of alcohol drinking on digestive tract carcinogenesis by decomposing the total effect of the ALDH2 Lys allele on digestive tract cancer risk into the two opposing effects of the carcinogenic effect (direct effect) and the protective effect (indirect effect mediated by drinking behavior). Alcohol was associated with an increased risk of most digestive tract cancers, but significant direct effects were observed only for upper gastrointestinal tract cancer risk, and varied substantially by site, with ORs (95% confidence interval) of 1.83 (1.43-2.36) for head and neck cancer, 21.15 (9.11-49.12) for esophageal cancer, and 1.65 (1.38-1.96) for stomach cancer. In contrast, a significant protective indirect effect was observed on risk for all cancers, except small intestine cancer. These findings suggest that alcohol is a major risk factor for digestive tract cancers, but its impact as a surrogate for acetaldehyde exposure appears heterogeneous by site. Meanwhile, the behavior-related effect of the ALDH2 Lys allele results in a decreased risk of most digestive tract cancers. SIGNIFICANCE: These findings support that genetic alcohol avoidance is a factor against alcohol-induced cancers.

Association between interleukin-10 -592 A/C polymorphism and gastrointestinal tract cancer risk: A meta-analysis.

Recent evidence suggests that -592 A/C polymorphism in the interleukin-10 (IL-10) gene may influence risk of gastrointestinal tract cancer; however, individual studies have provided conflicting and inconclusive results. Therefore, this meta-analysis was conducted to assess the association between IL-10 -592 A/C polymorphism and gastrointestinal tract cancer susceptibility. EMBASE, PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched for case-control studies published before 1 May 2017. A total of 36 studies involving 8069 cases and 13,089 controls were included in the present meta-analysis according to the inclusion criteria. The random- or fixed-effect model was utilized to calculate pooled odds ratio (OR) with 95% confidence interval (CI), and to survey the association. By and large IL-10 -592 A/C (rs1800872) polymorphism was not associated with gastrointestinal cancer risk in five genetic models (A vs. C: OR 1.00; 95% CI 0.93, 1.08; POR = 0.960; AA vs. CC: OR 0.98; 95% CI 0.85, 1.14; POR = 0.835; CA vs. CC: OR 1.01; 95% CI 0.94, 1.08; POR = 0.776; AA+CA vs. CC: OR 1.03; 95% CI 0.94, 1.12; POR = 0.592; AA vs. CA+CC: OR 0.98; 95% CI 0.87, 1.10; POR = 0.666). Similar results were also achieved after stratification by the Hardy-Weinberg equilibrium, ethnicity, source of controls, and cancer type. The results of this meta-analysis indicated that there is no association between the IL-10 -592 A/C promoter polymorphism and gastrointestinal tract cancer susceptibility.

Bisphosphonate use and gastrointestinal tract cancer risk: Meta-analysis of observational studies

To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk. Systematic literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library to identify studies through January 2011. Search terms were "bisphosphonates" or trade names of the drugs, and "observational studies" or "cohort studies" or "case-control studies". Two evaluators reviewed and selected articles on the basis of predetermined selection criteria as followed: (1) observational studies (case-control or cohort studies) on bisphosphonate use; (2) with at least 2 years of follow-up; and (3) reported data on the incidence of cancer diagnosis. The DerSimonian and Laird random effects model were used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). Two-by-two contingency table was used to calculate the outcomes not suitable for meta-analysis. Subgroup meta-analyses were conducted for the type of cancer (esophageal, gastric and colorectal cancers). Sensitivity analyses were performed to examine the effect sizes when only studies with long-term follow-up (mean 5 years; subgroup 3 years) were included. Of 740 screened articles, 3 cohort studies and 3 case-control studies were included in the analyses. At first, 4 cohort studies and 3 case-control studies were selected for the analyses but one cohort study was excluded because the cancer outcomes were not categorized by type of gastrointestinal cancer. More than 124,686 subjects participated in the 3 cohort studies. The mean follow-up time in all of the cohort studies combined was approximately 3.88 years. The 3 case-control studies reported 3070 esophageal cancer cases and 15,417 controls, 2018 gastric cancer cases and 10,007 controls, and 11,574 colorectal cancer cases and 53,955 controls. The percentage of study participants who used bisphosphonate was 2.8% among the cases and 2.9% among the controls. The meta-analysis of all the studies found no significant association between bisphosphonate use and gastrointestinal cancer. Also no statistically significant association was found in a meta-analysis of long-term follow-up studies. There was no negative association between bisphosphonate use and the incidence of esophageal cancer in the overall analysis (RR 0.96, 95% CI: 0.65-1.42, I(2) = 52.8%, P = 0.076) and no statistically significant association with long-term follow-up (RR 1.74, 95% CI: 0.97-3.10, I(2) = 58.8%, P = 0.119). No negative association was found in the studies reporting the risk of gastric cancer (RR 0.89, 95% CI: 0.71-1.13, I(2) = 0.0%, P = 0.472). In case of colorectal cancer, there was no association between colorectal cancer and bisphosphonate use (RR 0.62, 95% CI: 0.30-1.29, I(2) = 88.0%, P = 0.004) and also in the analysis with long-term follow-up (RR 0.61, 95% CI: 0.28-1.35, I(2) = 84.6%, P = 0.011). Oral bisphosphonate use had no significant effect on gastrointestinal cancer risk. However, this finding should be validated in randomized controlled trials with long-term follow-up.

Tea, coffee, carbonated soft drinks and upper gastrointestinal tract cancer risk in a large United States prospective cohort study

The authors investigated the relationship between hot tea, iced tea, coffee and carbonated soft drinks consumption and upper gastrointestinal tract cancers risk in the NIH-AARP Study. During 2,584,953 person-years of follow-up on 481,563 subjects, 392 oral cavity, 178 pharynx, 307 larynx, 231 gastric cardia, 224 gastric non-cardia cancer, 123 Oesophageal Squamous Cell Carcinoma (ESCC) and 305 Oesophageal Adenocarcinoma (EADC) cases were accrued. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated by multivariate-adjusted Cox regression. Compared to non-drinking, the hazard ratio for hot tea intake of ⩾1 cup/day was 0.37 (95% CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95% CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last 3 years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95% CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods.

Colorectal Cancer Risks in Relatives of Young-Onset Cases: Is Risk the Same Across All First-Degree Relatives?

During the last 15 years, several single-gene mendelian disorders have been discovered that might account for some of the familial aggregation detected in large population studies of colorectal cancer (CRC). Mutations in DNA mismatch repair (MMR) genes cause hereditary nonpolyposis colorectal cancer-Lynch syndrome, the most common of the recognized CRC-predisposition syndromes, in which one major feature is a young age for cancer onset. However, for young-onset microsatellite stable (MSS) CRC, the familial risk for CRC is unknown. Patients with CRC who were <50 years old were identified through Minnesota Cancer Surveillance System (MCSS) and Mayo Clinic, Rochester, MN. CRCs in which the DNA MMR function was deficient as evidenced by high level microsatellite instability and/or loss of expression of MMR gene product by immunostaining were excluded. A total of 278 probands (131 from MCSS; 147 from Mayo Clinic) were included. Data on 1862 relatives were collected, of whom 68 were found to have had CRC, and an additional 165 had primary cancers of other types. Compared with Surveillance Epidemiology and End Results program data, relatives of young-onset CRC probands had increased risks for CRC. This relative risk (RR) was increased among first-degree relatives (RR, 1.65; 95% confidence interval [CI], 1.29-2.07) and was greater for siblings (RR, 2.67; 95% CI, 1.50-4.41) than parents (RR, 1.5; 95% CI, 1.14-1.94). We studied 278 probands with young-onset MSS CRC. We determined that the RR for CRC was greatest in siblings, which is consistent with an autosomal recessive inheritance pattern.

Prognosis in cystic fibrosis.

Prognosis for patients with cystic fibrosis has improved dramatically over the past three decades. In the United States, median survival age is now 28.9 years. Although genotype predicts exocrine pancreatic function, it does not correlate with pulmonary status or overall clinical outcome. However, there are a number of parameters, such as exocrine pancreatic sufficiency, male gender, absence of colonization with mucoid Pseudomonas aeruginosa, presentation with predominantly gastrointestinal symptoms, balanced family functioning and coping, and compliance with treatment regimens, that predict a more favorable outcome. The impact of early diagnosis and treatment is still controversial. Although nonblinded studies indicate decreased morbidity in the first 2 to 4 years of life among patients diagnosed by newborn screening, no data support long-term benefit in terms of pulmonary function or survival. With increased longevity, there is now evidence of a small but significantly increased risk of gastrointestinal tract cancer among patients with cystic fibrosis.

Aspirin Use and Reduced Risk of Gastrointestinal Tract Cancers in the American Cancer Society Prospective Studies

Aspirin Use and Reduced Risk of Gastrointestinal Tract Cancers in the American Cancer Society Prospective Studies

Asbestos: world concern, involvement and culpability

The general population is exposed to asbestos fibers stemming from a massive number of consumer products and from environmental pollution. Asbestos bodies are present in the lungs of many urban dwellers who do not work with the mineral. Heavy occupational exposure to asbestos is known to cause asbestosis, pleural calcification, pleural plaques, lung cancer, and pleural and peritoneal mesotheliomas. The ingestion of asbestos fibers may increase the risk of gastrointestinal tract cancer. At the present time, little is known about the hazards of chronic low‐level exposure to asbestos. However, the use of asbestos fibers should be curtailed whenever possible, more pathogenicity data should be collected and evaluated, and the health risk to the general public should be reassessed and updated with progressing research.