Risk Of Developing Colorectal Cancer Research Articles

Association Between rs1859168/HOTTIP Expression Level and Colorectal Cancer and Adenomatous Polyposis Risk in Egyptians.

LncRNA HOTTIP is a new lncRNA that is strictly linked to the susceptibility, growth, propagation, and prognosis of several human cancers together with colorectal cancer. lncRNA HOTTIP rs1859168 may confer colorectal cancer susceptibility through regulating its gene expression level. To elucidate its role in colorectal cancer risk, we genotyped rs1859168 A>C and measured serum HOTTIP expression level in colorectal cancer, adenomatous polyposis patients and controls by real-time polymerase chain reaction. The results displayed that rs1859168 A>C single-nucleotide polymorphism is a risk factor for colorectal cancer among adenomatous polyposis patients and controls, AC versus CC genotypes [adjusted odds ratio (OR) = 2.256, 95% confidence interval (CI) = 1.316-3.868, P = 0.003] when compared with controls and (adjusted OR = 9.521, 95% CI = 3.330-27.217, P < 0.0001) when compared with adenomatous polyposis. Serum HOTTIP was upregulated in the colorectal cancer group when compared with adenomatous polyposis or controls [median (interquartile range) = 3.64 (2.46-5.02) (P < 0.0001)]. A significant difference in serum HOTTIP was found to be associated with different rs1859168 genotypes. rs1859168 A>C and higher serum HOTTIP were significantly associated with distant metastasis, lymph nodes metastasis, and grade III of colorectal cancer. Both rs8159168 and high HOTTIP confer increased risk for colorectal cancer development. [Figure: see text].

The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.

Development of a microbially-derived therapy against Fusobacterium nucleatum, a bacterial pathogen linked with colorectal cancer

Background. Specific bacterial species have been linked to several intestinal diseases, including colorectal cancer (CRC). In recent years, high abundances of an emerging pathogen, Fusobacterium nucleatum, have been identified in tumors and stool samples of CRC patients and it has been suggested that F. nucleatum contributes to CRC initiation and development. The possibility of suppressing the growth of F. nucleatum in the GI tract using antimicrobial-producing probiotic bacteria may reduce the overall risk of CRC development. Methods. Here, we screen a collection of faecal samples from healthy donors against F. nucleatum in an effort to discover an antimicrobial-producing isolate capable of selectively inhibiting this emerging human pathogen. Potential isolates with anti-Fusobacterial activity were then further analysed for the ability to inhibit the pathogen in cell culture and in a faecal fermentation system, which simulates the dynamic conditions of the human colon. Results. Culture-based screening of over 16,000 colonies of gastrointestinal origin resulted in the identification of one faecal isolate with probiotic potential displaying significant antagonistic activity against F. nucleatum initially in cell culture media and subsequently inhibition was confirmed in the simulated intestinal model. Conclusion. This study reveals that, a novel gut isolate demonstrates inhibition against the CRC-associated F. nucleatum in vitro and suppresses its growth in a model of the human distal colon. This is an important finding, suggesting the potential of a natural gut bacterium to supress the growth of a bacterial pathogen associated with CRC, which may contribute to reducing the overall risk of developing the disease.

Does Colon Polyp Surveillance Improve Patient Outcomes?

Colon polyp surveillance now accounts for 25% of all colonoscopies performed. The evidence that colonoscopy surveillance reduces colorectal cancer (CRC) incidence or mortality is weak. The biology of the baseline lesions and quality of the baseline exam are two primary factors contributing to post-colonoscopy CRC. Prior recommendations for surveillance were based largely on the likelihood that patients with adenomas would develop advanced adenomas, a surrogate for CRC. There is now evidence that baseline colonoscopy findings are strongly associated with the risk of incidence or death from CRC. This evidence provides a basis for updated evidence-based recommendations for surveillance. In addition, there is also growing evidence that the quality of the baseline exam is an important predictor of the likelihood of developing post-colonoscopy CRC.

Evaluation of the association between P53 codon 72 and P21 codon 31genetic polymorphisms within gastric and colorectal cancer risk in a Moroccan Cohort

AimThe aim of the current study was to explore the association between the p53 (Arg > Pro) (rs1042522) and p21 (Ser > Arg) (rs1801270) polymorphisms and gastric and colorectal cancers susceptibility among Moroccan population. MethodsThis case control study was conducted on 70 gastric cancer, 70 colorectal cancer patients and 70 healthy patients. The p53 (Arg > Pro) and p21 (Ser > Arg) polymorphisms were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assay. ResultsFor the P53 codon 72 the genotype frequencies were 27.1% for Arg/Arg, 65,7% for Arg/Pro and 7,1% for Pro/Pro in control group, and 40%; 17,1% for Arg/Arg, 34.3%; 42,9% for Arg/Pro and 25,7%; 40% for Pro/Pro respectively in the gastric and colorectal cancer patients. Genotype frequencies of the p21 codon 31 were 17.1% for Arg/Arg, 71.4% for Ser/Arg and 11.4% for Ser/Ser in control group, and 22.9%; 25.7% for Arg/Arg, 35.7%; 41.4% and 41.4%; 32.9% for Ser/Ser respectively in the patient with gastric and colorectal cancer. This difference was statistically significant for the Pro/Pro genotype. The same trend as observed in the Pro allele distribution for colorectal cancer patients (P = 0.0004). No statistically significant correlation was found between p21 (Ser > Arg) and the development of gastric and colorectal cancers. ConclusionOur results have demonstrated that the P53 (rs1042522) polymorphism may contribute to the risk of colorectal cancer development while the P21 (rs1801270) polymorphism does not contribute to this susceptibility for both cancers in the Moroccan population.

Abstract 1206: Inhibition of GPR4 attenuates intestinal inflammation in a mouse colitis model

Abstract Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the digestive tract, is associated with a higher risk of colorectal cancer development. Current therapeutic approaches for IBD are limited and primarily include biologics and steroids such as anti-TNFα monoclonal antibodies and glucocorticoids. Chronic usage, however, can cause significant adverse drug effects such as increased risk of infection and lymphoma in some patients. GPR4, a pH-sensing G protein-coupled receptor, has recently emerged as a potential therapeutic target for intestinal inflammation. Previous studies demonstrate that GPR4 is a pro-inflammatory receptor expressed in vascular endothelial cells (EC) and stimulates leukocyte-EC adhesion and extravasation. Knockout of GPR4 alleviates intestinal inflammation in IBD mouse models. In this study, we have assessed the effects of a recently developed GPR4 antagonist, 2-(4-((2-Ethyl-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)phenyl)-5-(piperidin-4-yl)-1,3,4-oxadiazole (GPR4 antagonist 13, also known as NE 52-QQ57), in the dextran sulfate sodium (DSS)-induced acute colitis mouse model. The GPR4 antagonist 13 inhibited intestinal inflammation. All colitis parameters, such as body weight loss, fecal score, colon shortening, splenic expansion, and mesenteric lymph node enlargement, were reduced in the GPR4 antagonist 13 treatment group compared to the vehicle group. Histopathological features of active colitis and inflammatory gene expression of colon tissues were reduced in the GPR4 antagonist 13 treatment group compared to vehicle control. Our results indicate that the GPR4 antagonist 13 provides a protective effect in the DSS-induced colitis mouse model and inhibition of GPR4 can be explored as a novel anti-inflammatory approach. Citation Format: Edward J. Sanderlin, Mona Marie, Juraj Velcicky, Pius Loetscher, Li V. Yang. Inhibition of GPR4 attenuates intestinal inflammation in a mouse colitis model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1206.

Abstract 1343: SNPs in the NFKB alternative pathway genes CD40, BAFFR and LTβR in CRC

Abstract We sought to assess the role of single nucleotide polymorphisms (SNPs) in genes of the alternative NF-KB pathway, important in regulating different aspects of immune functions in colorectal cancer (CRC). The study comprised DNA samples from 418 patients with CRC and 299 age-matched healthy individuals. Genotyping was performed with real time PCR followed by high resolution melt curve analysis for the following SNPs: CD40 rs1883832 (C/T), BAFFR rs7290134 (A/G), LTβR rs10849448 (A/G). Genotypes of random samples were confirmed by sequencing. Genotype frequencies differed between CRC and healthy individuals for CD40 rs1883832 and LTβR rs10849448 (p = 0.001 and p = 0.016, respectively) but were similar for BAFFR rs7290134. The LTβR rs10849448 G allele was more frequent in CRC patients compared to healthy controls and increased risk for CRC by 61% (p = 0.024). Moreover, the G allele was found more frequently in stage D patients compared to stages A and C while the A allele was more prevalent in stage B patients (p = 0.007). Additionally, most patients with grade III tumors were G allele carriers whereas the majority of grade I tumors were AA homozygotes (p = 0.019). The CD40 rs1883832 T allele was less frequent in CRC patients and reduced risk for CRC by 71% (p = 0.027). The CD40 rs1883832 SNP proved to be a prognostic factor for PFS with the CC individuals displaying a longer PFS compared to T carriers (p = 0.045). The BAFFR rs7290134 SNP was independent of all clinical parameters evaluated. Primary site was independent of genotypes for all three SNPs. SNPs within genes of receptors of the NF-KB alternative pathway, CD40 rs1883832 and LTβR rs10849448, influence PFS and risk for CRC development. Additionally, particular genotypes correlated with stage and grade. Citation Format: Anna Antonacopoulou, Anastasia Kottorou, Angelos Koutras, Foteinos-Ioannis Dimitrakopoulos, Thomas Makatsoris, Haralabos P. Kalofonos. SNPs in the NFKB alternative pathway genes CD40, BAFFR and LTβR in CRC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1343.

Metformin inhibits β-catenin phosphorylation on Ser-552 through an AMPK/PI3K/Akt pathway in colorectal cancer cells.

Several epidemiologic studies have revealed strong inverse associations between metformin use and risk of colorectal cancer development. Nevertheless, the underlying mechanisms are still uncertain. The Wnt/β-catenin pathway, which plays a central role in intestinal homeostasis and sporadic colorectal cancer development, is regulated by phosphorylation cascades that are dependent and independent of Wnt. Here we report that a non-canonical Ser552 phosphorylation in β-catenin, which promotes its nuclear accumulation and transcriptional activity, is blocked by metformin via AMPK-mediated PI3K/Akt signaling inhibition.

LEPR polymorphisms and haplotypes in Mexican patients with colorectal cancer.

Obesity and colorectal cancer could be linked by adipocytokines, which are proteins associated with cell proliferation. High levels of the adipocytokine leptin promote the development of colorectal cancer through its receptor. To determine the association between c.326A>G and c.668A>G LEPR gene polymorphisms and colorectal cancer. DNA was extracted from the peripheral blood of 147 patients with sporadic colorectal cancer and 134 healthy people. Genotypes were obtained by PCRRFLP and the association was determined by the odds ratio (OR) test using the SPSS™, version 10.0, program. Haplotype frequencies and linkage disequilibrium were estimated by the Arlequin, version 3.5, software. Both polymorphisms were in Hardy-Weinberg equilibrium. Only the c.326A>G heterozygous genotype revealed an increased risk for colorectal cancer development (OR=1.81, 95% CI=1.04-3.16, p=0.04). The AG haplotype showed a significant association with colorectal cancer (OR=0.58, 95% CI=0.35-0.96, p<0.03). Linkage disequilibrium between the variants was only evident for the patients group (r2=0.36). Our results suggest that AG individuals heterozygous for the c.326A>G LEPR variant have a higher risk of colorectal cancer development whereas the AG haplotype (c.326A/c.668G) has a protective effect in the Mexican population.

Non-Alcoholic Fatty Liver Disease as a Risk for Colorectal Cancer Development and the Role of Screening Colonoscopy in Clinical Practice

Non-Alcoholic Fatty Liver Disease as a Risk for Colorectal Cancer Development and the Role of Screening Colonoscopy in Clinical Practice

Deletion and Single Nucleotide Polymorphisms in Common Glutathione-S Transferases Contribute to Colorectal Cancer Development

Glutathione-S transferases (GSTs) are xenobiotic-conjugation enzymes involved in the detoxification process of heterocyclic aromatic amines and polycyclic aromatic hydrocarbons, widely recognized risk factors of colorectal cancer (CRC) development. Polymorphism in GSTs often leads to alteration or complete lack of enzyme activity, which might have an effect on CRC carcinogenesis. Aim of this study was to investigate GST gene variants as risk factors in patients with CRC. A total of 523 CRC patients administered for surgical resection and 400 matched controls were included. Deletion polymorphism of GSTs M1 and T1 was investigated by polymerase chain reaction. Single nucleotide polymorphism of GST A1 and P1 was investigated by restriction fragment length polymorphism method. The association between GST genotype and risk of CRC development was found in carriers of GSTT1-null and GSTP1-variant genotypes individually (p = 0.050 and p = 0.016, respectively). Furthermore, statistically significant association was found when combination of GSTP1-variant genotype with any of other three common GST genotypes was analyzed with respect to CRC susceptibility. Additionally, patients with combined GSTM1-null/GSTT1-null/GSTA1 low-activity/GSTP1-variant genotype showed 2.71-fold increased risk of developing CRC (p = 0.037). This study supports hypothesis that GST polymorphisms might have an important role in the process of the CRC development. Additionally, GSTM1-null/ GSTT1-null/ GSTA1 low-activity/ GSTP1-variant genotype could be combination of GST genotypes whose carriers are more prone to CRC development.

Impact of Family History on Prognosis of Patients with Sporadic Colorectal Cancer.

A family history (FH) of colorectal cancer (CRC) increases the risk for development of CRC, but the impact of FH of CRC on survival from sporadic CRC is unclear. This study investigated the prognostic impact of FH of CRC on the recurrence and survival of patients with sporadic CRC. We reviewed the records of patients with sporadic CRC from two tertiary referral hospitals in Korea who underwent surgical resection between May 2007 and September 2013. The clinicopathologic features and oncologic outcomes of those with and without FHs of CRC were compared. We examined the records of 2960 eligible patients, 163 (5.5%) of whom had first-degree relatives with CRC. Patients with and without FHs of CRC had similar baseline characteristics. Multivariable analysis indicated that a FH of CRC was not significantly associated with disease-free survival but was significantly associated with better overall survival (OS) [adjusted hazard ratio = 0.539, 95% confidence interval (CI) 0.330-0.881, P = 0.014]. Subgroup analysis indicated that females and rectal cancer patients with FHs of CRC had significantly better prognoses. Microsatellite status did not affect the improved survival rate associated with FH. This study of patients with sporadic CRC indicated that those who had FHs of CRC had better OS but similar cancer recurrence as those who had no FH of CRC. The effect of FH of CRC on OS was independent of microsatellite status. Further studies are needed to identify underlying mechanisms and determine the optimal clinical management of CRC according to FH.

Incidence and outcome of colorectal cancer in liver transplant recipients: A national, multicentre analysis on 8115 patients.

De novo malignancies after liver transplantation represent one of the leading causes of death in the long-term. It remains unclear whether liver transplant recipients have an increased risk of colorectal cancer and whether this negatively impacts on survival, particularly in those patients affected by primary sclerosing cholangitis and ulcerative colitis. In this national multicentre cohort retrospective study, the incidence of colorectal cancer in 8115 evaluable adult patients undergoing a liver transplantation between 1 January 1990 and 31 December 2010 was compared to the incidence in the general population through standardised incidence ratios. Fifty-two (0.6%) cases of colorectal cancer were identified at a median of 5.6years postliver transplantation, predominantly grade 2 (76.9%) and stage T3 (50%) at diagnosis. The incidence rate of colorectal cancer in the whole liver transplant population was similar to the general UK population (SIR: 0.92), but significantly higher (SIR: 7.0) in the group of patients affected by primary sclerosing cholangitis/ulcerative colitis. One-, five- and ten-year survival rates from colorectal cancer diagnosis were 71%, 48% and 31%, respectively, and the majority of colorectal cancer patients died of cancer-specific causes. Liver transplantation alone is not associated with an increased risk of colorectal cancer development. The primary sclerosing cholangitis/ulcerative colitis liver transplant population showed a significantly higher risk of colorectal cancer development than the general population, with a high proportion of advanced stage at diagnosis and a reduced patient survival.

Significance of LDL and HDL subclasses characterization in the assessment of risk for colorectal cancer development.

IntroductionDyslipidaemia contributes to the occurrence of colorectal cancer (CRC). We hypothesized that qualitative changes of lipoproteins are associated with the risk for CRC development. This study analyses low-density lipoprotein (LDL) and high-density lipoprotein (HDL) diameters, as well as distribution of LDL and HDL subclasses in patients with CRC, with an aim to determine whether advanced lipid testing might be useful in predicting the risk for the onset of this malignancy.Materials and methodsThis case-control study included 84 patients with newly diagnosed CRC and 92 controls. Gradient gel electrophoresis was applied for separation of lipoprotein subclasses and for LDL and HDL diameters determination. Lipid parameters were measured using routine enzymatic methods.ResultsTotal cholesterol, HDL and LDL-cholesterol were significantly lower in CRC patients compared to controls (4.47 mmol/L vs. 5.63 mmol/L; 0.99 mmol/L vs. 1.27 mmol/L; 2.90 mmol/L vs. 3.66 mmol/L; P < 0.001, respectively). Patients had significantly smaller LDL (25.14 nm vs. 26.92 nm; P < 0.001) and HDL diameters (8.76 nm vs. 10.17 nm; P < 0.001) and greater proportion of small, dense LDL particles (54.0% vs. 52.9%; P = 0.044) than controls. Decreased LDL and HDL diameters were independent predictors of CRC (OR = 0.5, P = 0.001 and OR = 0.5, P = 0.008, respectively), and alongside with age and HDL-cholesterol concentrations formed the optimal cost-effective model, providing adequate discriminative abilities for CRC (AUC = 0.89) and correct patients classification (81%).ConclusionsPatients with CRC have decreased LDL and HDL diameters and increased proportion of smaller particles. LDL and HDL diameters determination could be useful in assessing the risk for CRC development.

Association of PARK2 promoter polymorphisms and methylation with colorectal cancer in North Indian population

Different diseases have been associated with PARK2/PACRG overlapping promoter polymorphisms (rs2276201 and rs9347683) in the recent past. However association of these polymorphisms with cancer remains elusive till date. Thus in this study we evaluated association between these polymorphisms and colorectal cancer (CRC) incidences among North Indians. Genomic DNA was isolated using venous blood of 400 unrelated subjects (200 CRC cases and 200 healthy controls) of North Indian origin. Both SNPs were genotyped using PCR-RFLP method. Promoter methylation status in tumor DNA was checked using MS-PCR. Statistical analysis was performed using SPSS-17 software. In-silico predictions for transcription factor binding were performed using “PROMO” a freely available online tool. SNP rs2276201 showed statistically significant difference (P = 0.047) among cases and controls while rs9347683 did not (P = 0.113). The TC genotype (OR: 1.855, 95% CI: 1.021–3.369, P = 0.043), CC genotype (OR: 1.617, 95% CI: 1.042–2.510, P = 0.032), TT vs CT+CC genetic model (OR: 1.60, P = 0.0158) and allelic model (OR: 1.3931, 95% CI: 1.0498–1.8485, P = 0.0214) of rs2276201 showed significant risk for CRC. For rs9347683 AC genotype (OR: 1.604, 95% CI: 1.019–2.523, P = 0.041) and AA vs AC+CC genetic model (OR: 1.57, P = 0.039) showed significant risk. Haplotype CC provided significant risk (OR: 1.618, 95% CI: 1.112–2.352, P = 0.011) whereas haplotype TA provided significant protection (OR: 0.732, 95% CI: 0.543–0.987, P = 0.040) against CRC. Promoter methylation was significantly higher in tumor grade III + IV (OR: 2.37, P = 0.019), while PARK2 expression was lower in cancer tissues compared to normal tissue. Here we provide the first report where PARK2 promoter SNP's rs2276201 and rs9347683 are shown to be significantly associated with the risk of CRC development.

Life After Surgery: Surgeon Assessments of Quality of Life Among Patients With Familial Adenomatous Polyposis.

Without prophylactic surgery, patients with familial adenomatous polyposis are at high risk for colorectal cancer development. Various surgical options for prophylaxis are available. Patient decision-making for preventative treatments is often influenced by the preferences of healthcare providers. We determined surgeon preferences for the surgical options available to patients with familial adenomatous polyposis. We obtained preference estimates for postoperative health states from colorectal surgeons who had treated ≥10 patients with familial adenomatous polyposis. Assessments were made at an annual meeting of the American Society of Colon and Rectal Surgeons. Utilities were measured through the time trade-off method. We determined utilities for 3 procedures used for prophylaxis, including total proctocolectomy with permanent ileostomy, colectomy with ileorectal anastomosis, and total proctocolectomy with IPAA. We also assessed utilities for 2 short-term health states: 90 days with a temporary ileostomy and 2 years with a poorly functioning ileoanal pouch. Twenty-seven surgeons who had cared for >1700 patients with familial adenomatous polyposis participated in this study. The highest utility scores were provided for colectomy with ileorectal anastomosis (0.98). Lower utility scores were provided for total proctocolectomy with permanent ileostomy (0.87) and IPAA (0.89). The number of patients with familial adenomatous polyposis who were treated by participating surgeons did not influence these estimates; however, more-experienced surgeons gave lower utility scores for a poorly functioning ileoanal pouch than less-experienced surgeons (0.15, 0.50, and 0.25 for high-, medium-, and low-volume surgeons; p = 0.02). This study was limited by the sample size. For patients with familial adenomatous polyposis and relative rectal sparing, surgeon preferences are greatest for colectomy with ileorectal anastomosis. Utility estimates provided by this study are important for understanding surgical decision-making and suggest a role for ileorectal anastomosis in appropriately selected patients. See Video Abstract at http://links.lww.com/DCR/A656.

Inhibitory effects of pentoxifylline on inflammation-related tumorigenesis in rat colon

Chronic inflammation in the colorectum increases the risk of colorectal cancer development. Pentoxifylline, a medicine used for improving the circulation, has been reported to inhibit TNF-α production and to ameliorate inflammatory bowel disease and non-alcoholic steatohepatitis. In this study, we investigated the effects of pentoxifylline on inflammation-related colon tumorigenesis in a rodent model using Kyoto APC delta rats, which have APC mutation and are susceptible to colon carcinogenesis. Male Kyoto APC delta rats were treated with azoxymethane and dextran sodium sulfate, and were subsequently administered water, with or without pentoxifylline. At the end of the experiment, the development of colorectal tumor was significantly inhibited in the pentoxifylline group. The pentoxifylline treatment also lowered the levels of oxidative stress markers and mRNAs of pro-inflammatory cytokines, including TNF-α and IL-6, in the colon mucosa. The PCNA labeling index and the inflammation score were also decreased in the colon of rats in the pentoxifylline -treated group. We also used an endoscopy to observe the tumor progression and inflammation in the colon of rats, revealing that inflammation grade was significantly lower in pentoxifylline-treated group at several points during the experiment. These findings suggest that pentoxifylline treatment might be useful for chemoprevention of inflammation-related colon cancer.

PO-102 Pre-diagnostic serum calcium concentrations and risk of colorectal cancer development in a prospective european cohort

IntroductionHigher intake levels of dietary calcium have been shown to be associated with decreased risk of colorectal cancer (CRC) development in several prospective studies. However, very little information is available on the CRC risk association of circulating calcium concentrations, particularly since elevated serum calcium has been associated in some settings with metabolic dysfunction and diabetes, factors which appear to be related to higher CRC risk.Material and methodsIn order to explore this question, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between serum calcium levels and the risk of colorectal cancer (CRC) development. 975 first incident CRC cases were matched to 975 matched controls from within the cohort by sex, age, study centre, length of follow-up and some additional relevant variables. Serum calcium levels were measured using reflection X-ray fluorescence spectrometry on the pre-diagnostically-collected serum samples from cases and matched controls.Conditional logistic regression was used to calculate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CIs).Results and discussionsHigher levels of serum calcium were associated with reduced risk of CRC (OR Q5vs.Q1=0.69, 95% CI: 0.48–0.99; p trend=0.02). Sub-group analyses by anatomical sub-site suggest that the observed inverse cancer risk association is apparent in the colon (OR Q5vs.Q1=0.61, 95% CI: 0.38–0.98; p trend=0.04) and not in the rectum (OR Q5vs.Q1=0.99, 95% CI: 0.53–1.85; p trend=0.54) where the association appeared to be non-linear. The magnitude of the association in the colon is similar to that observed with dietary calcium at the same anatomical site. Stratified analysis by sex is suggestive of a stronger association for men than women.ConclusionIn conclusion, elevated serum calcium levels are inversely associated with risk of CRC development, with some evidence for heterogeneity by anatomical sub-site and sex. Additional studies are necessary to confirm these findings and to further investigate potential underlying mechanisms for the role of serum calcium in CRC development.

Association between Nonsteroidal Anti-Inflammatory Drugs and Colorectal Cancer: A Population-Based Case-Control Study.

Background: COX-2 overexpression may contribute to colorectal cancer occurrence. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce colorectal cancer recurrence, but the efficacy of primary prevention in Asian populations is still elusive. Thus, we examined the primary preventive efficacy of aspirin and NSAIDs on colorectal cancer incidence in Taiwan.Methods: A nested case-control study was conducted using the National Health Insurance Research Database (NHIRD) in Taiwan. We identified patients with diagnosis of colorectal cancer from 2005 to 2013 in the Registry of Catastrophic Illness Patient Database. We selected patients without colorectal cancer from the Longitudinal Health Insurance Database as the controls and matched them with cases. NSAID exposure was defined as at least two prescriptions 13 to 48 months prior to the index date. Conditional logistic regression models were performed to evaluate the association between NSAID use and colorectal cancer.Results: A total of 65,208 colorectal cancer cases and 65,208 matched controls were identified. Patients with aspirin use had a lower risk of colorectal cancer compared with nonusers [adjusted OR (AOR) = 0.94, 95% confidence interval (CI) = 0.90-0.99]. NSAID use was associated with lower incidence of colorectal cancer (AOR = 0.96; 95% CI = 0.92-1.00). When examining colon or rectal cancer, similar decreased risks were observed. Patients taking more cumulative days of NSAIDs use tended to experience a more protective effect on colorectal cancer, but no dose-response effects were noted.Conclusions: Aspirin and NSAIDs were associated with a reduced risk of colorectal cancer development among a study cohort in an Asian population.Impact: This study provided a possible chemoprevention for colorectal cancer in an Asian population. Cancer Epidemiol Biomarkers Prev; 27(7); 737-45. ©2018 AACR.

PO-103 Can we eat to prevent colorectal cancer?

IntroductionHigher intake levels of dietary calcium have been shown to be associated with decreased risk of colorectal cancer (CRC) development in several prospective studies. However, very little information is available on the CRC risk association of circulating calcium concentrations, particularly since elevated serum calcium has been associated in some settings with metabolic dysfunction and diabetes, factors which appear to be related to higher CRC risk.Material and methodsIn order to explore this question, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between serum calcium levels and the risk of colorectal cancer (CRC) development. 975 first incident CRC cases were matched to 975 matched controls from within the cohort by sex, age, study centre, length of follow-up and some additional relevant variables. Serum calcium levels were measured using reflection X-ray fluorescence spectrometry on the pre-diagnostically-collected serum samples from cases and matched controls.Conditional logistic regression was used to calculate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CIs).Results and discussionsHigher levels of serum calcium were associated with reduced risk of CRC (OR Q5vs.Q1=0.69, 95% CI: 0.48–0.99; p trend=0.02). Sub-group analyses by anatomical sub-site suggest that the observed inverse cancer risk association is apparent in the colon (OR Q5vs.Q1=0.61, 95% CI: 0.38–0.98; p trend=0.04) and not in the rectum (OR Q5vs.Q1=0.99, 95% CI: 0.53–1.85; p trend=0.54) where the association appeared to be non-linear. The magnitude of the association in the colon is similar to that observed with dietary calcium at the same anatomical site. Stratified analysis by sex is suggestive of a stronger association for men than women.ConclusionIn conclusion, elevated serum calcium levels are inversely associated with risk of CRC development, with some evidence for heterogeneity by anatomical sub-site and sex. Additional studies are necessary to confirm these findings and to further investigate potential underlying mechanisms for the role of serum calcium in CRC development.