Risk Of Digestive Cancers Research Articles

Cyclooxygenase-2 promoter 765C increase of digestive tract cancer risk in the Chinese population: a meta-analysis.

To evaluate relationship between the cyclooxygenase-2 promoter 765G/C polymorphism and digestive cancer risk in China. A literature search through February 2014 was performed using PubMed, Chinese Biomedical Literature Database (CBM) and China National Knowledge Infrastructure (CNKI) databases, and a meta-analysis was performed with RevMan 5.2 software for odds ratios and 95%CIs. In total, 9 articles with 3,263 cases and 4,858 controls were included in this meta-analysis.The pooled OR (95%CIs) in the co-dominant model (GC vs GG) was 1.56 [1.19, 2.06], and in the dominant model ((CC+GC) vs GG), the pooled OR was 1.59 [1.21, 2.09] in overall cancers. In the subgroup analysis, stratified by cancer type, significant associations were found that the-765C allele had increased pancreatic cancer and gastric risk. No significant liver cancer and colorectal cancer risk of COX-2 -765G/C polymorphism was found. These findings suggest that COX-2-765*C is related to cancer susceptibility and may increase gastric and pancreatic cancer risk.

Meta-analysis of association studies of CYP1A1 genetic polymorphisms with digestive tract cancer susceptibility in Chinese.

A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancer susceptibility in Chinese populations. Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed- effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Eighteen case control studies with 1, 747 cases and 2, 923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/ Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [ GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG ]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancer risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancer risk in Chinese population. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

Fas -670A/G (rs1800682) polymorphism and digestive cancer risk in Asians: a meta-analysis.

Tumorigenesis is a multistep process that begins with the abrogation of normal controls of apoptosis and cell proliferation, and the Fas receptor-ligand system is a key regulator of apoptosis. The Fas -670 A/G single-nucleotide polymorphism (SNP) has been demonstrated to affect the expression of the Fas gene by altering the transcriptional activity in this gene's promoter. However, the association between the Fas -670 A/G polymorphism and digestive cancer risk is still controversial and ambiguous in the Asian population, so we conducted a meta-analysis to confirm and clarify the association between the Fas -670 A/G polymorphism and digestive cancer. A search of PubMed, China National Knowledge Infrastructure (CNKI), and WanFang databases was conducted and encompassed all available articles that had been published up to July 20, 2013. Overall, 15 case-control studies containing 3692 cases and 4895 controls were retrieved based on search criteria for digestive cancer susceptibility related to -670A/G SNP. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. In the overall analysis, the country type and source of control subgroups, no association between the Fas -670 A/G polymorphism and digestive cancer risk was found. However, in the digestive cancer-type subgroups, a significant protective effect was detected between Fas -670 A/G polymorphism and hepatocellular carcinoma in Asians (AG vs. GG: OR=0.89, 95% CI=0.80-0.99; AA+AG vs. GG: OR=0.93, 95% CI=0.87-1.00). Our investigations demonstrated that the Fas -670 A/G polymorphism might decrease the hepatocellular carcinoma risk in Asian populations. Further studies based on larger sample sizes, other ethnicities, and gene-environment interactions should be conducted to further understand the role of Fas -670 A/G polymorphism in digestive cancer risk.

The effect of XPD polymorphisms on digestive tract cancers risk: a meta-analysis.

BackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionsOur meta-analysis suggested that the XPD 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations.

Nutrition and metabolic factors in cancer causation and prevention

EPIC represents a large and mature resource for epidemiological studies of cancer aetiology. Data can be integrated from studies on diet, physical activity, anthropometry and biomarker measurements to build a broad picture of the role of nutrition and metabolic factors in cancer causation. Since the initial baseline collection, cohort participants have been followed up to obtain information on changes in major dietary and lifestyle factors including a series of questions on whether the subjects had suffered from a number of common diseases and medical conditions. So far, over 60,000 newly incident cancer cases have been reported, including around 14,000 breast, 3,600 lung, 5,200 colorectal, 1,180 pancreatic, and 1,400 endometrial cancer cases, giving scope for well-powered studies on cancer causation. Some notable findings from EPIC research include the association between fibre consumption and a reduced risk in the development of colorectal cancer, red meat consumption and an increased risk of digestive tract cancers, positive associations with BMI and colon cancer in men, waist-hip ratio and the development of colon cancer in both men and women and a significant prediction between being overweight (expressed as BMI) and breast cancer risk in postmenopausal women not using HRT. It is clear that a number of chemical, physical and biological carcinogens have a major role in cancer causation and in some cases account for most of the variations in cancer incidence across the world. However, they cannot explain the global variations for a large number of cancers that represent a significant proportion of the world’s total cancer burden. Research conducted during past decades, and particularly those based on large prospective studies including EPIC, has found that diet, nutrition physical activity and anthropometry have major influences on population risk of cancer. From a scientific point of view, the unravelling of the mechanistic effects underlying the increased cancer risk associated with some components of current western diet and lifestyle is challenging. The effect may be due to fine modulation or modest dis-regulation of normal physiological processes rather than gross disruption, as may be the case for some strong exogenous carcinogens. From a public health point of view, these metabolic lifestyle factors are of great interest as they largely overlap with the major known risk factors of cardiovascular diseases and diabetes, therefore offering the opportunity of targeting the prevention of a number of non-communicable diseases with the same panel of public health interventions.

Emergency department utilization can indicate early diagnosis of digestive tract cancers: A population-based study in Taiwan

Background and objectivePatients who visit emergency department (ED) may have symptoms of occult cancers. MethodsWe studied a random cohort of one million subjects from Taiwan National Health Insurance Research Database between 2000 and 2008 to evaluate the ED utilization of individuals who were subsequently diagnosed with digestive tract cancers. The case group was digestive tract cancer patients and the control group was traumatic fracture patients. We reviewed record of ED visits only from 4 to 15 months before the cancer diagnoses. ResultsThere were 2635 and 6665 in the case and control groups respectively. Patients’ adjusted odds ratio with 95% confidence interval for the case group were 1.36 (1.06–1.74) for Abdominal ultrasound, 2.16 (1.61–2.90) pan-endoscopy, 1.72 (1.33–2.22) guaiac fecal-occult blood test, 1.42 (1.28–1.58) plain abdominal X-rays, 1.20 (1.09–1.32) SGOT, 1.27 (1.14–1.40) SGPT, 1.66 (1.41–1.95) total bilirubin, 2.41 (1.89–3.08) direct bilirubin, 1.21 (1.01–1.46) hemoglobin and 3.63 (2.66–4.94) blood transfusion, respectively. Blood transfusion in the ED was a significant predictor of the individual subsequently diagnosed with digestive tract cancer. ConclusionsThe health system could identify high risk patients early by real-time review of their ED utilization before the diagnosis of digestive tract cancers. We proposed a follow-up methodology for daily screening of patients with high risk of digestive tract cancer by informatics system in the ED.

Mortality and extraintestinal cancers in patients with primary sclerosing cholangitis and inflammatory bowel disease

IntroductionPrimary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) frequently co-occur. PSC is associated with increased risk for colorectal cancer (CRC). However, whether PSC is associated with increased risk of extraintestinal cancers or affects mortality in an IBD cohort has not been examined previously. MethodsIn a multi-institutional IBD cohort of IBD, we established a diagnosis of PSC using a novel algorithm incorporating narrative and codified data with high positive and negative predictive value. Our primary outcome was occurrence of extraintestinal and digestive tract cancers. Mortality was determined through monthly linkage to the social security master death index. ResultsIn our cohort of 5506 patients with CD and 5522 patients with UC, a diagnosis of PSC was established in 224 patients (2%). Patients with IBD–PSC were younger and more likely to be male compared to IBD patients without PSC; three-quarters had UC. IBD–PSC patients had significantly increased overall risk of cancers compared to patients without PSC (OR 4.36, 95% CI 2.99–6.37). Analysis of specific cancer types revealed that a statistically significant excess risk for digestive tract cancer (OR 10.40, 95% CI 6.86–15.76), pancreatic cancer (OR 11.22, 95% CI 4.11–30.62), colorectal cancer (OR 5.00, 95% CI 2.80–8.95), and cholangiocarcinoma (OR 55.31, 95% CI 22.20–137.80) but not for other solid organ or hematologic malignancies. ConclusionsPSC is associated with increased risk of colorectal and pancreatobiliary cancer but not with excess risk of other solid organ cancers.

Lynch Syndrome

Colorectal cancer is a rare disease in the pediatric age group and, when present, suggests an underlying genetic predisposition. The most common hereditary colon cancer susceptibility condition, Lynch syndrome (LS), previously known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant condition caused by a germline mutation in 1 of 4 DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. The mutation-prone phenotype of this disorder is associated with gastrointestinal, endometrial, and other cancers and is now being identified in both symptomatic adolescents with malignancy as well in asymptomatic mutation carriers who are at risk for a spectrum of gastrointestinal and other cancers later in life. We review the DNA MMR system, our present understanding of LS in the pediatric population, and discuss the newly identified biallelic form of the disease known as constitutional mismatch repair deficiency syndrome. Both family history and tumor characteristics can help to identify patients who should undergo genetic testing for these cancer predisposition syndromes. Patients who carry either single allele (LS) or double allele (constitutional mismatch repair deficiency syndrome) mutations in the MMR genes benefit from cancer surveillance programs that target both the digestive and extraintestinal cancer risk of these diseases. Because spontaneous mutation in any one of the MMR genes is extremely rare, genetic counseling and testing are suggested for all at-risk family members.

HIF1A gene Pro582Ser polymorphism and susceptibility to digestive tract cancers: a meta-analysis of case-control studies.

Many existing studies have demonstrated that common polymorphisms in the hypoxia inducible factor-1α (HIF-1A) may contribute to the development of digestive tract cancers, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a precise estimation of the relationships between HIF1A Pro582Ser polymorphism and the risk of digestive tract cancers. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through May 1, 2013. Meta-analysis was performed using the STATA 12.0 software. We assessed 6 case-control studies that included a total of 911 digestive tract cancer patients and 2774 healthy controls. Our meta-analysis indicated that HIF1A Pro582Ser polymorphism was associated with an increased risk of digestive tract cancer. Subgroup analysis by ethnicity suggested that HIF1A Pro582Ser polymorphism might increase an individual's susceptibility to digestive tract cancer in Asian populations. However, similar association was not observed in Caucasian populations. In conclusion, our findings suggest that HIF1A Pro582Ser polymorphism may contribute to the risk of digestive tract cancers, especially in Asian populations.

Common polymorphisms in the HIF-1α gene confer susceptibility to digestive cancer: a meta-analysis.

Recent evidence suggests that common functional polymorphisms in the hypoxia inducible factor-1α (HIF-1α) gene may play an important role in the development and progression of digestive cancer, but individually published results are inconclusive. Our meta-analysis is aimed to derive a more precise estimation of the relationships between HIF-1α gene polymorphisms and digestive cancer risk. An extensive literature search for relevant studies was conducted on Pubmed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence interval (CI) were calculated. Eight case-control studies were included with a total of 1276 digestive cancer patients and 3392 healthy controls. Our meta-analysis revealed that the A variant of HIF-1α G1790A polymorphism might be associated with increased risk of colorectal, esophageal, gastric, and liver cancers, especially among Asian populations. However, no statistically significant associations were found between HIF-1α C1772T polymorphism and susceptibility to digestive cancer. No publication bias was detected in this meta-analysis. The current meta-analysis suggests that the HIF-1α G1790A polymorphism may increase the risk of colorectal, esophageal, gastric, and liver cancers, especially among Asian populations.

Lack of any Association between Insertion/Deletion (I/D) Polymorphisms in the Angiotensin-converting Enzyme Gene and Digestive System Cancer Risk: a Meta-analysis

To investigate the association between the gene polymorphisms of angiotensin-converting enzyme (ACE) and digestive system cancer risk. A search was performed in Pubmed, Medline, ISI Web of Science and Chinese Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical analysis was performed by using Revman5.2 and STATA 12.0. A total of 15 case-control studies comprising 2,390 digestive system cancer patients and 9,706 controls were identified. No significant association was found between the I/D polymorphism and digestive cancer risk (OR =0.93, 95%CI = (0.75, 1.16), P =0.53 for DD+DI vs. II). In the subgroup analysis by ethnicity and cancer type, no significant associations were found for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated a lack of associations between this polymorphism and digestive system cancer risks. This meta-analysis suggested that the ACE D/I polymorphism might not contribute to the risk of digestive system cancer.

Association between PTEN IVS4 polymorphism and cancer risk: A meta-analysis

PTEN, a candidate tumor suppressor gene, has been identified within chromosome 10q23 and plays an important role in tumorigenesis. The association between the IVS4 insertion/deletion (I/D) polymorphism of PTEN and cancer risk in several populations has been studied, but results are conflicting. The aim of the present study was to investigate association of PTEN IVS4 polymorphism with cancer risk by conducting a meta-analysis. A literature search was conducted through PubMed, Chinese National Knowledge Infrastructure (CNKI) and WanFang databases (up to October 18, 2013). Six eligible studies with 2,179 cases and 3,132 controls were enrolled in the meta-analysis. The pooled odds ratio (OR) and 95% confidence intervals (CI) were used to assess the strength of association. Our results indicated that the~polymorphism conferred a significantly decreased risk of overall cancer (dominant model: OR=0.87, 95% CI 0.77-0.99; recessive model: OR=0.83, 95% CI: 0.72-0.96; II vs. DD model: OR=0.79, 95% CI: 0.67-0.94; I vs. D model: OR=0.89, 95% CI: 0.82-0.97). Subgroup analysis by cancer type and ethnicity furtherly showed that PTEN gene IVS4 polymorphism was associated with decreased risk of digestive cancers (recessive model: OR=0.77, 95% CI: 0.64-0.92; II vs. DD model: OR=0.72, 95% CI: 0.58-0.91; I vs. D model: OR=0.84, 95% CI: 0.76-0.94), this strong association with reduced risk of cancer was also found in Asian population (recessive model: OR=0.83, 95% CI: 0.71-0.98; II vs. DD model: OR=0.79, 95% CI: 0.65-0.96; I vs. D model: OR=0.89, 95% CI: 0.81-0.98). In conclusion, our meta-analysis suggested that PTEN IVS4 polymorphism might play a protective role in the development of cancer, further independent confirmation of associations observed in PTEN IVS4 polymorphism by more studies was necessary.

Association between zinc intake and risk of digestive tract cancers: A systematic review and meta-analysis

Association between zinc intake and digestive tract cancers risk has been reported in several epidemiological studies, while the results were controversial. The aim of our study was to get a systemic review of this issue. PUBMED and EMBASE were searched up to April 2013, supplemented with manual-screening for relevant articles. Two independent reviewers independently extracted data from eligible studies, risk ratio (RR) or odds ratio (OR) with 95% CIs for the highest versus lowest categories of zinc intake was adopted. Either a fixed- or a random-effects model was adopted to estimate overall odds ratios. Besides, dose-response, subgroup, and publication bias analyses were applied. Nineteen studies with approximately 400,000 participants were included in this meta-analysis. The pooled relative risk (RR) of overall digestive tract cancers for the highest versus lowest categories of zinc intake was 0.82 (95% CI: 0.70-0.96; p = 0.013). Comparing the highest with lowest categories, higher zinc intake was significantly associated with reduced colorectal cancer risk (pooled RR = 0.80, 95% CI: 0.70-0.92; p = 0.002), while zinc intake was not statistically associated with gastric cancer risk (pooled RR = 0.91, 95% CI: 0.64-1.29; p = 0.581) or esophageal cancer risk (pooled RR = 0.72, 95% CI: 0.44-1.17; p = 0.187). However, subgroup analyses showed that zinc intake was significantly associated with esophageal cancer risk and gastric cancer risk in Asia, but not in America and Europe. Dietary zinc intake was inversely associated with digestive tract cancers, especially colorectal cancer risk in this study.

Increased Risk of Developing Digestive Tract Cancer in Subjects Carrying the PLCE1 rs2274223 A>G Polymorphism: Evidence from a Meta-Analysis

BackgroundTo date, the association between phospholipase C epsilon 1 (PLCE1) rs2274223 A>G and risk of digestive tract cancer (DTC) remains inconclusive. To derive a more precise estimation of the association, we conducted a meta-analysis on all eligible case–control studies involving 8281 cases and 10,532 controls.MethodsA comprehensive search was conducted to identify all eligible studies of PLCE1 rs2274223 polymorphism and digestive tract cancer risk. The pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated using a fixed or random effect model. Heterogeneity, publication bias, and sensitivity analysis were also explored.ResultsOverall, the PLCE1 rs2274223 A>G polymorphism was associated with risk of DTC in all genetic models (GA vs. AA: OR = 1.21, 95% CI = 1.14–1.29, P<0.001; GG vs. AA: OR = 1.30, 95% CI = 1.06–1.60, P = 0.012; GG/GA vs. AA: OR = 1.20, 95% CI = 1.10–1.32, P<0.001; GG vs. GA/AA: OR = 1.21, 95% CI = 1.01–1.46, P = 0.040). The recessive model did not reach statistically significance when the P values were Bonferroni corrected to 0.0125. In the stratified analysis by cancer type, ethnicity, and source of controls, significantly increased risk was observed for esophagus cancer, Asians in three genetic models (heterozygote comparison, homozygote comparison and dominant model), population-based studies in all genetic models, and for gastric cancer in the heterozygote comparison and dominant model after Bonferroni correction. However, in the subsite of gastric cancer, no significant association was found either in cardia or non-cardia gastric cancer.ConclusionOur study indicated that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of DTC, especially among Asian populations. Due to some minor limitations, our findings should be confirmed in further studies.

ALDH2 Genotype Has No Effect on Salivary Acetaldehyde without the Presence of Ethanol in the Systemic Circulation

BackgroundAcetaldehyde associated with alcoholic beverages was recently classified as carcinogenic (Group 1) to humans based on uniform epidemiological and biochemical evidence. ALDH2 (aldehyde dehydrogenase 2) deficient alcohol consumers are exposed to high concentrations of salivary acetaldehyde and have an increased risk of upper digestive tract cancer. However, this interaction is not seen among ALDH2 deficient non-drinkers or rare drinkers, regardless of their smoking status or consumption of edibles containing ethanol or acetaldehyde. Therefore, the aim of this study was to examine the effect of the ALDH2 genotype on the exposure to locally formed acetaldehyde via the saliva without ethanol ingestion.MethodsThe ALDH2 genotypes of 17 subjects were determined by PCR-RFLP. The subjects rinsed out their mouths with 5 ml of 40 vol% alcohol for 5 seconds. Salivary ethanol and acetaldehyde levels were measured by gas chromatography.ResultsAcetaldehyde reached mutagenic levels rapidly and the exposure continued for up to 20 minutes. The mean salivary acetaldehyde concentrations did not differ between ALDH2 genotypes.ConclusionsFor ALDH2 deficient subjects, an elevated exposure to endogenously formed acetaldehyde requires the presence of ethanol in the systemic circulation.ImpactOur findings provide a logical explanation for how there is an increased incidence of upper digestive tract cancers among ALDH2 deficient alcohol drinkers, but not among those ALDH2 deficient subjects who are locally exposed to acetaldehyde without bloodborne ethanol being delivered to the saliva. Thus, ALDH2 deficient alcohol drinkers provide a human model for increased local exposure to acetaldehyde derived from the salivary glands.

NBS1 Glu185Gln polymorphism and cancer risk: update on current evidence

A number of studies have investigated the association between NBS1 Glu185Gln (rs1805794, E185Q) polymorphism and cancer risk, but the results remained controversial. Previous meta-analysis found a borderline significant impact of this polymorphism on cancer risk; however, the result might be relatively unreliable due to absence of numerous newly published studies. Thus, we conducted an updated meta-analysis. A systematic search was performed in PubMed and Embase databases until April 9, 2013. The odds ratios were pooled by the fixed-effects/random-effects model in STATA 12.0 software. As a result, a total of 48 case-control studies with 17,159 cases and 22,002 controls were included. No significant association was detected between the Glu185Gln polymorphism and overall cancer risk. As to subgroup analysis by cancer site, the results showed that this polymorphism could increase the risk for leukemia and nasopharyngeal cancer. Notably, the Glu185Gln polymorphism was found to be related to increased risk for urinary system cancer, but decreased risk for digestive system cancer. No significant associations were obtained for other subgroup analyses such as ethnicity, sample size and smoking status. In conclusion, current evidence did not suggest that the NBS1 Glu185Gln polymorphism was associated with overall cancer risk, but this polymorphism might contribute to the risk for some specific cancer sites due to potential different mechanisms. More well-designed studies are imperative to identify the exact function of this polymorphism in carcinogenesis.

Higher glycemic index and glycemic load diet is associated with increased risk of esophageal squamous cell carcinoma: a case-control study

Several studies have indicated the association between intake of foods high in dietary glycemic index (GI) and glycemic load (GL) with an increased risk of digestive tract cancers. We hypothesized that GI and GL may be associated with risk of esophageal squamous cell carcinoma (ESCC) in a high-risk population in Iran. In total, we interviewed 47 cases with incident of ESCC and 96 frequency-matched hospital controls, then calculated the average dietary GI and GL via a validated food frequency questionnaire. Dietary GL was calculated as a function of GI, carbohydrate content, and frequency of intake of certain foods. Dietary GI and GL levels were significantly higher among the ESCC cases compared with the controls (P < .05). After adjustment for potential confounders, those in the highest tertile of dietary GI had 2.95 times higher risk of ESCC compared with those in the lowest (95% confidence interval, 1.68-3.35; P for trend = .002). In addition, being in the highest tertile of dietary GL was positively associated with an ESCC risk (odds ratio, 3.49; 95% confidence interval, 2.98-4.41; P for trend = .001). Findings of the present study indicate that diets with high GI and GL might have potentially unfavorable effects on ESCC risk and suggest a possible role for excess circulating insulin and related insulin-like growth factor 1 in esophageal cancer development.

Quantitative assessment of the influence of cytochrome P450 2C19 gene polymorphisms and digestive tract cancer risk

Cytochrome P450 (CYP) 2C19 metabolizes many promutagens and procarcinogens to biologically active metabolites, which strongly promote proliferation of cancer cells in vitro and in vivo. The CYP2C19 gene exhibits several genetic polymorphisms that are thought to play a major role in inter-individual variability in drug response, drug-xenobiotic interactions, and in cancer susceptibility. Two polymorphisms of the CYP2C19 gene (CYP2C19*2, CYP2C19*3) which was associated with reduced enzyme activity have been investigated extensively digestive tract cancer; however, these studies have yielded contradictory results. To clarify this inconsistency, we performed this meta-analysis including 15 case-control studies with a total of 3,252 cases and 6,269 controls. Overall, we found significant association between CYP2C19*2 and digestive tract cancer (OR = 1.27, 95 % CI, 1.07-1.51, P = 0.007) while no significant results were found for CYP2C19*3. Potential sources of heterogeneity including cancer types, ethnicity, source of control, and sample size of study were assessed. In the subgroup analyses by cancer types, significant association was detected only in esophagus cancer for CYP2C19*2. When stratified by ethnicity, significantly increased risks were found for the CYP2C19*2 polymorphism among Asians. This meta-analysis demonstrated that the CYP2C19*2 polymorphism is a risk factor for developing digestive tract cancer. However, additional very large-scale studies are warranted to provide conclusive evidence on the effects of the CYP2C19 gene on risk of digestive tract cancer.

Pre-miR-27a rs895819A/G Polymorphisms in Cancer: A Meta-Analysis

BackgroundMicroRNAs (miRNAs) negatively regulate the 3′ untranslated region (3′-UTR) of coding genes by suppressing translation or degrading mRNAs, and they act as oncogenes or tumor suppressors. Recently, several studies investigated the association between pre-miR-27a rs895819 polymorphism and the risks of various cancers, but the results were inconsistent.Methodology/Principal FindingsWe conducted a meta-analysis of 13 studies that included 6501 cancer cases and 7571 controls to address this association. Overall, this meta-analysis showed that the pre-miR-27a rs895819 A/G polymorphism was not statistically associated with cancers risk in all genetic models. In the stratified analysis by cancer types, when compared with the ancestral A allele, individuals with the variant G allele was consistently associated with reduced risks of breast cancer (OR = 0.92, 95% CI = 0.85–0.99), renal cell cancer (OR = 0.81, 95% CI = 0.67–0.97) and nasopharyngeal cancer (OR = 0.84, 95% CI = 0.72–0.97). Inversely, individuals with the heterozygote AG was associated with an increased risk of digestive tract cancers compared with AA genotype (AG vs. AA: OR = 1.16, 95% CI = 1.01–1.32). In the stratified analysis by ethnicity, the pre-miR-27a rs895819 polymorphism showed statistically significant association with decreased risks of cancers in Caucasians (G vs. A allele: OR = 0.90, 95% CI = 0.83–0.97; AG vs. AA: OR = 0.84, 95% CI = 0.75–0.94; AG/GG vs. AA: OR = 0.85, 95% CI = 0.76–0.94) but not in Asians.Conclusion/SignificanceThis meta-analysis suggests that the pre-miR-27a rs895819 polymorphism may contribute to the susceptibilities of some specific-type of cancers, including breast cancer, renal cell cancer, nasopharyngeal cancer and digestive tract cancers, as well as the susceptibilities of cancers in Caucasians to some extent.

Association between promoters polymorphisms of matrix metalloproteinases and risk of digestive cancers: a meta-analysis

A variety of studies have been performed to elucidate the polymorphisms in promoter regions of matrix metalloproteinases (MMPs) associated with the risk of digestive cancers, and yet, results remain conflicting and heterogeneous. Thus, we undertook a systematic meta-analysis to determine the genetic susceptibility of MMPs to digestive cancers. A computerized literature search was conducted in databases of PubMed, Embase, and ISI Web of Knowledge till October 2012 for any MMP genetic association study in oral squamous, gastric, esophageal, and colorectal carcinomas. Odds ratios (OR) and 95% confidence interval (CI) were estimated for each gene under dominant and recessive models, and the heterogeneity between studies was assessed using Q test and I (2) value. Overall and subgroup analysis according to anatomical sites and ethnicity was carried out. Statistical analysis was performed with Review Manager 5.0. A total of 40 eligible publications with 68 comparisons were included in this study. For MMP1 nt-1607, individuals with 2G state could increase risk of digestive cancers in total analysis (dominant: OR=1.31, 95% CI=1.16-1.48, P<0.00001; recessive: OR=1.29, 95% CI=1.11-1.50, P=0.0009). In the subgroup of tumor sites, significant associations were also observed in esophageal cancer and colorectal cancer under both genetic models. For MMP2 nt-1306, CT or TT carriers performed significant protection against digestive cancer in the dominant model (OR=0.69, 95% CI=0.55-0.85, P=0.0007) of the overall. In the subgroup analysis, significant association was found in esophageal cancer, with borderline effects in gastric cancer and oral squamous cell carcinoma. For MMP7 -181 A/G, significant association was observed under two genetic models in the overall (dominant: OR=1.26, 95% CI=1.10-1.43, P=0.0009; recessive: OR=1.33, 95% CI=1.11-1.60, P=0.002) and in the individual cancer subgroup of esophageal cancer and gastric cancer. For MMP9 -1,562 C/T, a borderline effect was found with digestive cancers in the total and stratified analysis of the colorectal cancer under dominant model. No association was observed in either the overall or subgroup analysis for MMP3 -1,171 5A/6A. Our meta-analysis demonstrated the fact that polymorphisms in promoter regions of MMP genes might be related to the susceptibility of digestive cancers, with cancer development for MMP1 and MMP7, and a protection against cancer for MMP2 and MMP9. Further evidences with adequate sample sizes need to be conducted.