Risk Of Colorectal Carcinoma Research Articles

Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum

Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and tumor necrosis factor-receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on an empiric dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with the presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment. We calculated EDIP scores based on answers to food frequency questionnaires collected from participants in the Nurses' Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a polymerase chain reaction assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status. During 28 years of follow-up evaluation of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores were associated with increased risk of F nucleatum-positive colorectal tumors (Ptrend= .03); for subjects in the highest vs lowest EDIP score tertiles, the hazard ratio for F nucleatum-positive colorectal tumors was 1.63 (95% CI, 1.03-2.58). EDIP scores did not associate with F nucleatum-negative tumors (Ptrend= .44). High EDIP scores associated with proximal F nucleatum-positive colorectal tumorsbut not with proximal F nucleatum-negative colorectal tumors (Pheterogeneity= .003). Diets that may promote intestinal inflammation, based on EDIP score, are associated with increased risk of F nucleatum-positive colorectal carcinomas, but not carcinomas that do not contain these bacteria. These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis; nutritional interventions might be used in precision medicine and cancer prevention.

Body Mass Index and Other Anthropomorphic Variables in Relation to Risk of Colorectal Carcinoma Subtypes Classified by Tumor Differentiation Status

Metabolic energy dysregulation may affect intestinal epithelial cell homeostasis, and thus promote colorectal carcinogenesis. Yet, little is known about the association between obesity and enterocyte differentiation during tumor development.We hypothesized that an association between anthropomorphic measurements and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Anthropomorphic variables evaluated included Body Mass Index (BMI), Hip circumference (HC), Waist circumference (WC), and Waist‐Hip Ratio (WHR).Using data from the Nurses' Health Study and Health Professionals' Follow‐up Study, and performing duplication‐method Cox proportional hazard models, we prospectively examined an association between BMI, mean waist/hip circumference (WC/HC), and waist‐hip ratio (WHR) with the incidence of colorectal carcinoma subtypes classified by differentiation status. 120,813 participants were followed for 26 or 32 years and 1528 colorectal cancer cases with available tumor pathological data were documented.The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly differentiated tumor foci (Pheterogeneity = 0.006). Higher BMI was associated with higher risk of colorectal carcinoma without poorly differentiated foci (≥30.0 vs. 18.5–22.4 kg/m2: multivariable‐adjusted hazard ratio, 1.87; 95% confidence interval, 1.49–2.34; Ptrend <0.001), but not with risk of carcinoma with poorly‐differentiated foci (Ptrend = 0.56). While in men, high WC, HC, and WHR were associated with overall incidence of colorectal carcinoma (Ptrend ≤ 0.01), there was no statistically significant association between these variables and tumor differentiation status (Pheterogeneity >0.27). Furthermore, the association between anthropomorphic variables and colorectal carcinoma did not differ significantly by overall tumor grade, mucinous differentiation, or the presence of a signet‐ring‐cell component (PHeterogeneity > 0.03, with the adjusted α of 0.01). The differential association of BMI with tumor differentiation appeared to be consistent in strata of tumor microsatellite instability and fatty acid synthase (FASN) expression, although statistical power was limited.Whilst BMI was associated with increased risk of the colorectal cancer subtype lacking poorly differentiated foci, there was no independent association between tumor differentiation and measures of central adiposity. Our findings suggest that the carcinogenic effect of generalized excess body adiposity may be stronger for tumors that retain greater degrees of intestinal differentiation.Support or Funding InformationThis work was supported by U.S. National Institutes of Health (NIH) grants (P01 CA87969 to M.J. Stampfer; UM1 CA186107 to M.J. Stampfer; P01 CA55075 to W.C. Willett; UM1 CA167552 to W.C. Willett; U01 CA167552 to W.C. Willett and L.A. Mucci; P50 CA127003 to C.S.F.; R01 CA118553 to C.S.F.; R01 CA169141 to C.S.F.; R01 CA137178 to A.T.C.; K24 DK098311 to A.T.C.; R35 CA197735 to S.O.; R01 CA151993 to S.O.; K07 CA190673 to R.N.; and K07 CA188126 to X.Z.); by Nodal Award from the Dana‐Farber Harvard Cancer Center (to S.O.); and by grants from the Project P Fund, The Friends of the Dana‐Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance, and by Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant (to C.S.F. and M.Gi.). J.B. was supported by the Australia Awards‐Endeavour Scholarships and Fellowships Program. K.K. was supported by grants from Overseas Research Fellowship (JP2017–775) from Japan Society for the Promotion of Science. T.H. was supported by a fellowship grant from the Mitsukoshi Health and Welfare Foundation.T.H. was supported by a fellowship grant from the Mitsukoshi Health and Welfare Foundation. L.L. was supported by a scholarship grant from Chinese Scholarship Council and a fellowship grant from Huazhong University of Science and Technology. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Association of microRNA-423 rs6505162 C>A polymorphism with susceptibility and metastasis of colorectal carcinoma.

Studies have evaluated the association between the SNP miRNA-423 rs6505162 C>A and cancer risk in several cancers with contradictory outcomes. It was reported that miRNA-423 rs6505162 C>A polymorphism was associated with the overall survival and the recurrence-free survival of colorectal carcinoma. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of colorectal carcinoma.In this study, we investigated the association between miRNA-423 polymorphism with risk and clinicopathological parameters of colorectal carcinoma. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype 117 colorectal carcinoma patients and 84 healthy controls.Our data indicated the frequencies of rs6505162 genotypes and alleles were significantly different between colorectal carcinoma patients and controls. Compared with CC homozygote, the AC heterozygote exhibited a significantly decreased risk of colorectal carcinoma; and the combination of AC and AA genotype was associated with decreased risk of colorectal carcinoma. The allele distribution of rs6505162 was significantly different between cases and controls. Furthermore, miR-423 rs6505162 C>A genotype showed a significant association with metastasis in patients (P = .022).Our study suggested that miR-423 rs6505162 C>A polymorphism was associated with the susceptibility and metastasis of colorectal carcinoma, and that miR-423 rs6505162 C>A polymorphism might be a potential biomarker for colorectal carcinoma.

Interaction of smoking and metabolic syndrome in increasing the recurrence risk of colorectal cancer in a Chinese male cohort: a retrospective study

Whether smoking and metabolic syndrome (MetS) can affect colorectal carcinoma (CRC) prognosis remains debatable. Therefore, the present study aimed to examine the individual and combined effects of smoking and MetS on the prognosis of patients with localized CRC, including stage I to III disease. The relationship among smoking status, MetS, and CRC was assessed in 838 Chinese male patients. Cox proportional hazards regression analysis was used to evaluate CRC prognosis adjusted for clinicopathological variables. Relative excess risk of interaction (RERI), attributable proportion (AP), and synergy index (SI) were used to evaluate additive interactions between smoking and MetS. The presence of MetS was an independent risk factor for low rates of recurrence-free survival (RFS) but not for overall survival (OS). However, smoking was independently associated with both poor RFS and OS. Furthermore, the recurrence risk for current smokers with MetS was 1.62 times as high as the sum of risks in patients exposed to each risk factor alone. In conclusion, current smoking habit is a risk factor for both recurrence and cancer-specific mortality in CRC patients, while MetS is an independent predictor for CRC recurrence. Furthermore, these two factors have an additive effect on the recurrence risk of CRC.

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Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor

Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions. We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses' Health Study (since 1976) and the Health Professionals Follow-Up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes). During follow-up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (Ptrend= .02), and varied with degree of peritumoral lymphocytic reaction (Pheterogeneity < .001). Higher EDIP scores were associated with increased risk of colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio, 2.60; 95% confidence interval, 1.60-4.23; Ptrend < .001), but not risk of tumors with intermediate or highperitumoral lymphocytic reaction (Ptrend > .80). In 2 prospective cohort studies, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral lymphocytic reaction. These findings suggest that diet-related inflammation might contribute to development of colorectal cancer, by suppressing the adaptive anti-tumor immune response.

Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia

Background:Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma.Methods:Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia. Findings from the study are also compared with previously published genome wide and exome sequencing data in inflammatory bowel disease-associated and sporadic colorectal carcinoma.Results:Next-generation sequencing analysis identified 1107 mutations in 275 genes in UCHR subjects. In addition to TP53 (17%) and KRAS (22%) mutations, recurrent mutations in APC (33%), ACVR2A (61%), ARID1A (44%), RAF1 (39%) and MTOR (61%) were observed in UCHR subjects. In addition, APC, FGFR3, FGFR2 and PIK3CA driver mutations were identified in UCHR subjects. Recurrent mutations in ARID1A (44%), SMARCA4 (17%), MLL2 (44%), MLL3 (67%), SETD2 (17%) and TET2 (50%) genes involved in histone modification and chromatin remodelling were identified in UCHR subjects.Conclusions:Our study identifies new oncogenic driver mutations which may be involved in the transition of non-dysplastic cells to dysplastic phenotype in the subjects with long-standing UC with high risk of progression into colorectal neoplasia.

Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status.

Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32years and 1528 rectal and colon cancer cases with available tumor pathological data were documented. The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly-differentiated foci (Pheterogeneity=0.006). Higher BMI was associated with a higher risk of colorectal carcinoma without poorly-differentiated foci (≥30.0 vs. 18.5-22.4kg/m2: multivariable-adjusted hazard ratio, 1.87; 95% confidence interval, 1.49-2.34; Ptrend<0.001), but not with risk of carcinoma with poorly-differentiated foci (Ptrend=0.56). This differential association appeared to be consistent in strata of tumor microsatellite instability or FASN expression status, although the statistical power was limited. The association between BMI and colorectal carcinoma risk did not significantly differ by overall tumor differentiation, mucinous differentiation, or signet ring cell component (Pheterogeneity>0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.

Sessile Serrated Polyps and Colon Cancer Prevention.

Evidence suggests that up to one fifth of colorectal carcinomas develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic colorectal carcinomas with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps. Dysplasia is detected in a subset of SSA/Ps with a high risk of progression to carcinoma. An uncommon serrated polyp is the traditional serrated adenoma that is typically found in the left colon, has a tubulovillous architecture, and frequently harbors mutant KRAS To date, the epidemiology of these serrated lesions is poorly understood, and limited observational data suggest a potential chemopreventive benefit of nonsteroidal anti-inflammatory drugs. The current primary strategy to reduce the risk of colorectal carcinoma from serrated polyps is to enhance their detection at colonoscopy and to ensure their complete removal. This review provides insight into the epidemiologic, clinical, histopathologic, and molecular features of serrated polyps and includes data on their endoscopic detection and chemoprevention. Cancer Prev Res; 10(5); 270-8. ©2017 AACR.

Obesity Surgery and the Risk of Colorectal Carcinoma—Searching for the Fly in the Ointment?

Obesity Surgery and the Risk of Colorectal Carcinoma—Searching for the Fly in the Ointment?

An update on cancer risk and surveillance in primary sclerosing cholangitis.

Malignancy represents substantial morbidity and mortality in patients with primary sclerosing cholangitis (PSC). This subset of patients has been proven to be at increased risk for developing cholangiocarcinoma, gallbladder carcinoma and colorectal cancer in those with overlapping inflammatory bowel disease. Herein, we review the prevalence of these malignancies and recommend screening tools and current knowledge to reduce the disease burden in this population. Cholangiocarcinoma is the most dominant malignancy affecting PSC patients, with a lifetime risk ranging from 5% to 20%. We advocate for serial US or MRI/MRCP and CA 19-9 to screen for cholangiocarcinoma. Gallbladder cancer has a lifetime risk around 2% in this population and we agree with annual imaging for lesions as recommended by national guidelines. Patients with PSC and concomitant IBD are at increased risk of colorectal carcinoma from time of diagnosis and therefore should likely undergo annual surveillance. The low rates of hepatocellular cancer and pancreatic cancer indicate surveillance for these malignancies is less advantageous.

Colorectal Polyposis in a 15 Year Old Boy in Uganda - Case Report

Colorectal polyps usually present as rectal bleeding and are associated with increased risk of colorectal carcinoma. This is a 15 year old boy who presented with painless rectal bleeding for 9 years and mass protruding from the anus for 2 years after passing stool. He had history of 3 nephews with similar symptoms. On clinical assessment an impression of Adematous familial colorectal polyposis was made and biopsy was taken from the mass that revealed inflammatory polyps. He subsequently had a total colectomy and ileall pouch anal anastomosis with good outcome. In absence of endoscopic surveillance and diagnostic services diagnosis of colorectal polyposis syndromes is a challenge because clinicians rely on digital rectal assessment and examination under anesthesia.Key words: polyposis, polyps, Uganda

The Association between Lifestyle, Occupational, and Reproductive Factors and Colorectal Cancer Risk

Objective:Association of lifestyle, reproductive and environmental factors has been investigated with increased risk of colorectal cancer in different studies. We explored evidence and investigated association between various risk factors and colorectal cancer.Methods:This case- control study was conducted 155 colorectal cancer patients and 150 hospital-controls. We obtained detailed lifestyle, occupational, reproductive information from both groups. Chi-Square test and Logistic regression model were used to evaluate the risk factors of colorectal cancer.Results:The results showed that frequent intake of fruits, chicken, fish and alcohol drinking were associated with risk for colorectal cancer. Agricultural occupation (OR=7.003, 95% CI=2.19-22.38) and industrial exposure (OR=1.97, 95% CI=0.91-4.22) were associated significantly with risk for colorectal cancer. Regarding reproductive factors, women who reported less than 3 pregnancies was associated with an increased risk of colorectal carcinoma (OR=2.88, 95% CI=1.15-7.17). We did not find significant association between other reproductive factors and colorectal cancer risk in women after adjusting for demographic factors.Conclusion:In this case-control study we observed that agricultural occupation, industrial exposure and high consumption of fish and less than 3 pregnancies in women were associated with an increased risk of colorectal carcinoma.

Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical stage.

BackgroundNK cell cytotoxicity is regulated by the types of the interaction between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands on target cells and the different binding affinity of the Fcγ receptor IIIA (CD16A) for IgG-coated tumor cells. Thus, it is conceivable that KIR and CD16A gene contents may contribute to the function of NK cells by modulating an immune response in the colorectal carcinoma (CRC) microenvironment. This hypothesis is supported by recent evidence suggesting that NK cells improve the clinical course of CRC patients by enhancing the anti-CRC effect of CD8 + T cells. This information provides the rationale to test the hypothesis whether the independent KIR segregation and specificity, as well as CD16A gene polymorphisms, have an impact on CRC.MethodsUsing polymerase chain reaction-sequence-specific primers (PCR-SSP) and sequence-based typing (SBT), we investigated KIR/HLA-C complex and CD16A (48H/R/L,158V/F) gene polymorphisms in 52 CRC patients and 61 local healthy controls (LCTRs).ResultsThe allele frequency (AF) of at least five activating KIR (aKIRs) of the B haplotype (p = 0.036, OR 0.204), KIR2DL2 (p = 0.047, OR 0.2616), and KIR2DS2 genes (5.8 vs LCTR 13.8 % and vs. Fasano’s CTR 16.3 %, p = 0.05, OR 0.3145), in the absence of their cognate HLA-C1 ligands, were significantly associated with a reduced genetic risk of CRC. In contrast, CD16A-48H polymorphism was positively associated with an increased genetic risk of CRC (p = 0.05, OR 2.761). The latter was also found to be correlated with advanced stages of disease [III and IV (p = 0.03, OR 3.625)].ConclusionsOur data suggest that the analysis of aKIRs and KIR2DL2 gene and CD16A-48H may be of interest for the identification of individuals at reduced and increased genetic risk of CRC, respectively.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-1001-y) contains supplementary material, which is available to authorized users.

Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes

Aspirin use reduces colorectal cancerrisk. Aspirin, a nonsteroidal anti-inflammatory drug, inhibits prostaglandin-endoperoxide synthase 2 (PTGS2 or cyclooxygenase-2); PTGS2 promotes inflammation and suppresses T-cell-mediated adaptive immunity. We investigated whether the inverse association of aspirin use with colorectal carcinoma risk was stronger for tumors with lower degrees of lymphocytic infiltrates than for tumors with higher degrees of lymphocytic infiltrates. We collected aspirin use data biennially from participants in the Nurses' Health Study and Health Professionals Follow-up Study. Participants were asked whether they took aspirin in most weeks, the number of tablets taken per week, and years of aspirin use. We collected available tumor specimens (n= 1458) from pathology laboratories in the United States. A pathologist confirmed the diagnosis of colorectal adenocarcinoma (excluding anal squamous cell carcinoma), and evaluated histopathology features, including patterns and degrees of lymphocytic infiltrates within and around tumor areas. Person-years of follow-up evaluation were accrued from the date of return of questionnaires until dates of colorectal cancer diagnosis, death, or the end of follow-up evaluation (June 2010). Duplication-method Cox proportional hazards regression was used to assess the association of aspirin with the incidence of colorectal carcinoma subgroups according to the degree of tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral reaction, or Crohn's-like reaction. We documented 1458 rectal and colon cancers. The inverse association between regular aspirin use and colorectal cancer risk significantly differed by concentrations of TILs (Pheterogeneity= .007). Compared with nonregular use, regular aspirin use was associated with a lower risk of tumors that had low levels of TILs (relative risk, 0.72; 95% confidence interval, 0.63-0.81), and strength of the association depended on aspirin dose and duration (both Ptrend < .001). In contrast, aspirin use was not associated with a risk of tumors having intermediate or high levels of TILs. This differential association was consistent regardless of the status of tumor microsatellite instability, mutations in BRAF, or expression of PTGS2. Regular aspirin use was associated with a lower risk of tumors that contained low levels of CD3+ Tcells, CD8+ T cells, or CD45RO (PTPRC)+ T cells (measured by immunohistochemistry and computer-assisted image analysis). Based on data from the prospective cohort studies, regular use of aspirin is associated witha lower risk of colorectal carcinomas with low concentrations of TILs. These findings indicate that the immune response in thetumor microenvironment could be involved in the chemopreventive effects of aspirin.

Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate.

Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+) , CD8(+) , CD45RO (PTPRC)(+) or FOXP3(+) ] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (Ptrend < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (Pheterogeneity > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor.

GSTM1 gene polymorphism and the risk of colorectal cancer in a Saudi Arabian population.

The enzyme glutathione S-transferase Mu 1 (GSTM1) is encoded by the GSTM1 gene. Polymorphisms in GSTM1 affect the detoxifying function of the enzyme variants. This forms the basis of the debate about the impact of the GSTM1 null/present genotype on colorectal carcinoma risk. We tested the potential influence of GSTM1 polymorphisms on the development of colorectal cancer. DNA extracted from 83 samples taken from patients that were previously diagnosed as having colorectal carcinoma and from 35 control subjects who did not have colorectal carcinoma were amplified. GSTM1 genotypes were determined by DNA sequencing. The current study revealed that the majority (69/83, 83%) of colorectal cancer cases harbored the null genotype (GSTM1*0/*0), and the remaining 14 (17%) cases harbored either the GSTM1wt/wt or the GSTM1wt/*0 genotype. In contrast, among the control cases, 23 (65%) had the null genotype (GSTM1*0/*0) and 12 (35%) had either the GSTM1wt/wt or the GSTM1wt/*0 genotype. The current report emphasizes the impact of the GSTM1 null genotype on the increased risk of colorectal carcinoma in Saudi Arabia.

Helicobacter pylori infection and colorectal carcinoma risk: A meta-analysis.

Helicobacter pylori infection and colorectal cancer risk are not clear. We perform this meta-analysis to further evaluate the association between H. pylori infection and colorectal cancer susceptibility. The databases of CNKI, Wanfang, PubMed, Medline, EMBASE, and HighWire Press were electronic searched by two reviewers independently. The case-control study or cohort study about H. pylori infection and colorectal cancer risk were included in this meta-analysis. The association between H. pylori infection and colorectal cancer risk was evaluated by odds ratio (OR) and corresponding 95% confidence interval (95% CI). Fourteen case-control studies related to H. pylori infection and colorectal cancer risk were eventually include in this meta-analysis. The pooled results showed that H. pylori infection slight increase the risk of developing colorectal carcinoma (OR = 1.33, 95% CI: 1.01-1.77, P = 0.05). Moreover, Begg's funnel plot demonstrated no significant publication bias. Colorectal carcinoma is associated with H. pylori infection. However, for significant heterogeneity across the studies, this results should be further confirmed by large sample size cohort study.

The Association between miR-196a2 rs11614913 Polymorphism and Digestive System Cancer Risk: A Meta-Analysis of 34 Studies

Background: MicroRNAs (miRNAs) negatively regulate the gene expression and act as tumor suppressors or oncogenes in carcinogenesis. The association between single nucleotide polymorphism (SNP) in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies. Methods: A standardized search of PubMed, Embase, and Cochrane library databases for publications on miR-196a2 rs11614913 polymorphism and digestive system cancer risk was performed. Then the genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association. Test of heterogeneity, sensitivity analysis and assessment of publication bias were conducted in the present meta-analysis by STATA software 12.0. Results: An updated meta-analysis based on 34 independent case-control studies consisting of 13,013 cases and 16,046 controls was performed to address this association. There was a remarkable association between miR-196a2 rs11614913 polymorphism and overall digestive system cancer risk, especially in Asian populations. Moreover, subgroup analysis revealed that variant C allele increased risk of colorectal carcinoma, gastric cancer and hepatocellular carcinoma (HCC), compared with wild T allele. Conclusions: There was a remarkable association between miR-196a2 rs11614913 polymorphism and overall digestive system cancer risk, especially in Asian populations.

Immunohistochemical expression of proinflammatory enzyme COX-2 and p53 in ulcerative colitis and its associated dysplasia and colorectal carcinoma

Background/aimUlcerative colitis (UC) patients are at increased risk for colorectal carcinoma (CRC). It is suggested that cyclooxygenase-2 (COX-2) plays a role in sporadic CRC. The p53 gene is a tumor-suppressor gene and the most frequent site of genetic alteration found in human cancer. The aim of this study was to analyze the immunoexpression of proinflammatory enzyme COX-2 and p53 in UC, UC-associated dysplasia, and CRC, in comparison with each other and with different clinical and histopathological parameters, to clarify if they have a possible role in the pathogenesis of CRC in UC patients. Materials and methodsIn this cross-sectional study, 98 patients were divided into three groups: 39 patients with UC without dysplasia, 32 patients with UC with dysplasia, and 27 patients with colorectal cancer on top of UC, in addition to 10 healthy controls. All patients underwent colonoscopy, and multiple biopsies were taken for histopathological and COX-2 and p53 immunohistochemical studies. ResultsThere was significant difference in the expression of COX-2 and p53 in UC-related dysplasia either without or with CRC, compared with their expression in the UC group without dysplasia. ConclusionAdding immunohistochemical analysis of COX-2 enzyme and p53 gene to routine histological assessment may improve the accuracy of early detection of dysplasia and colorectal cancer. COX-2 and p53 can be promising chemotherapeutic/chemopreventive targets in UC patients.