Elevated Risk Of Colorectal Cancer Research Articles

Diabetes Mellitus and Site-specific Colorectal Cancer Risk in Korea: A Case-control Study.

Objectives:Previous large-scale cohort studies conducted in Korea have found a positive association between diabetes mellitus (DM) and colorectal cancer (CRC) in men only, in contrast to studies of other populations that have found significant associations in both men and women.Methods:A total of 1070 CRC cases and 2775 controls were recruited from the National Cancer Center, Korea between August 2010 and June 2013. Self-reported DM history and the duration of DM were compared between cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by binary and polytomous logistic regression models.Results:DM was associated with an elevated risk of CRC in both men (OR, 1.47; 95% CI, 1.13 to 1.90) and women (OR, 1.92; 95% CI, 1.24 to 2.98). This association remained when we controlled for age, body mass index, alcohol consumption, and physical activity level. In sub-site analyses, DM was associated with distal colon cancer risk in both men (multivariate OR, 2.04; 95% CI, 1.39 to 3.00) and women (multivariate ORs, 1.99; 95% CI, 1.05 to 3.79), while DM was only associated with rectal cancer risk in women (multivariate OR, 2.05; 95% CI, 1.10 to 3.82). No significant association was found between DM and proximal colon cancer risk in either men (multivariate OR, 1.45; 95% CI, 0.88 to 2.41) or women (multivariate OR, 1.79; 95% CI, 0.78 to 4.08).Conclusions:Overall, DM was associated with an increased risk of CRC in Koreans. However, potential over-estimation of the ORs should be considered due to potential biases from the case-control design.

Isoflavone and Soyfood Intake and Colorectal Cancer Risk: A Case-Control Study in Korea.

We aimed to assess the relationship between dietary soyfood and isoflavone intake and colorectal cancer risk in a case-control study. A total of 901 colorectal cancer cases and 2669 controls were recruited at the National Cancer Center, Korea. A semi-quantitative food frequency questionnaire was used to assess the usual dietary habits, and the isoflavone intake level was estimated from five soyfood items. A high intake of total soy products, legumes, and sprouts was associated with a reduced risk for colorectal cancer in men and women, although the middle quartiles of intake of total soy products were associated with an elevated risk. In contrast, a high intake of fermented soy paste was associated with an elevated risk for colorectal cancer in men. The groups with the highest intake quartiles of isoflavones showed a decreased risk for colorectal cancer compared to their counterparts with the lowest intake quartiles in men (odds ratio (OR): 0.67, 95% confidence interval (CI): 0.51–0.89) and women (OR: 0.65, 95% CI: 0.43–0.99). The reduced risk for the highest intake groups persisted for distal colon cancer in men and rectal cancer in women. The association between soyfood intake and colorectal cancer risk was more prominent among post-menopausal women than pre-menopausal women. In conclusion, a high intake of total soy products or dietary isoflavones was associated with a reduced risk for overall colorectal cancer, and the association may be more relevant to distal colon or rectal cancers.

Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Based on GWAS Results.

Genome-wide association studies (GWASs) and a number of case–control studies have suggested that several single nucleotide polymorphisms (SNPs), rs7837328, rs7014346, rs6983267, rs10505477 on CASC8 gene and rs4939827, rs4464148, rs12953717 on SMAD7 gene are significantly correlated with the susceptibility to colorectal cancer (CRC). For the sake of clarifying the association, a meta-analysis was conducted and population heterogeneity was considered in the study.A total of 34 articles including 90 studies (168,471 cases and 163,223 controls) that evaluated the relationship between the CASC8, SMAD7 genes and the risk of CRC under the allelic model were reviewed. Also subgroup analysis was performed by ethnicity (Caucasian, Asian, and African) and all of the analyses were implemented in R 3.2.1 software.Pooled data from the meta-analysis revealed that the A allele of rs7837328, the A allele of rs7014346, the G allele of rs6983267, the A allele of rs10505477, the T allele of rs4939827, the T of rs4464148, and the T of rs12953717 were significantly associated with an increased risk of CRC under the allelic model. Additionally, subgroup analyses of 6 SNPs by ethnicity (rs4464148 excepted) witnessed that the A allele of rs7837328, the G allele of rs6983267, and the T of rs12953717 were notably associated with an increased risk of CRC among Caucasian and Asian. Furthermore, the A allele of rs7014346, the A allele of rs10505477, and the T allele of rs4939827 were significantly related with an elevated risk of CRC only among Caucasian.Our study suggested that for CASC8 gene, SNP of rs7837328 and rs6983267 are risk factors for CRC among both Caucasian and Asian whereas rs7014346 and rs10505477 are risky gene polymorphisms only among Caucasian. For SMAD7 gene, rs4939827 and rs4464148 are risk factors for CRC among Caucasian whereas rs12953717 could elevate the susceptibility to CRC in both Caucasian and Asian.

Alcohol Drinking, Cigarette Smoking and Risk of Colorectal Cancer in the Korean Multi-center Cancer Cohort.

Background:The present study aimed to examine the association between cigarette smoking, alcohol consumption and colorectal cancer risk among Korean adults.Methods:Data from the Korean Multi-center Cancer Cohort between 1993 and 2005 were analyzed. The study population comprised 18,707 subjects aged older than 20 years old. The subjects were followed until December 31, 2011 (median follow-up of 11.2 years). The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence intervals of cigarette smoking and alcohol consumption for colorectal cancer risk.Results:In men, longer duration and higher average amount of alcohol consumption were associated with elevated risk of colorectal cancer (HR 1.93 [1.17–3.18] for ≥ 30 years of consumption compared to non-drinkers; HR 2.24 [1.31–3.84] for ≥ 30 g/d). Former smokers showed a non-significantly elevated risk of colorectal cancer in men. There was no apparent association between alcohol consumption or cigarette smoking and colorectal cancer risk among women.Conclusions:Alcohol consumption was associated with increased colorectal cancer risk among Korean men, and both a longer duration and a higher amount of consumption were associated with elevated risk.

Thyroid dysfunction, thyroid hormone replacement and colorectal cancer risk.

Current screening guidelines for colorectal cancer (CRC) do not consider thyroid dysfunction as a risk factor for disease development. We sought to determine the risk of developing CRC in patients with thyroid dysfunction, with and without thyroid hormone replacement (THR). We conducted a nested case-control study using a large population-based medical records database from the United Kingdom. Study case patients were defined as those with any medical code of CRC. Subjects with familial colorectal cancer syndromes or inflammatory bowel disease (IBD) were excluded. For every case patient, four eligible control patients matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence density sampling. Exposure was THR therapy before index date. We further divided the THR unexposed group into patients with hypothyroidism (TSH > 4 mg/dl), patients with hyperthyroidism (TSH < 0.4 mg/dl), and subjects without documented thyroid abnormality. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRC were estimated using conditional logistic regression. All statistical tests were two-sided. We identified 20990 CRC patients and 82054 control patients. The adjusted odds ratio for CRC associated with THR was 0.88 (95% CI = 0.79 to 0.99, P = .03) and 0.68 (95% CI = 0.55 to 0.83, P < .001) for treatment initiated five to 10 years and more than 10 years before index date, respectively. This protective association increased with cumulative duration of therapy. In contrast, hyperthyroidism (adjusted OR = 1.21, 95% CI = 1.08 to 1.36, P = .001) or untreated hypothyroidism (adjusted OR = 1.16, 95% CI = 1.08 to 1.24, P < .001) were associated with increased risk of CRC. Long-term THR is associated with a decreased risk of CRC. Hyperthyroidism and untreated hypothyroidism are associated with modestly elevated risk of CRC.

Mo1962 Post-Market Analysis of the Use and Effectiveness of GTA-446, a Blood Test That Identifies Persons With Elevated Colorectal Cancer Risk, in Ontario, Canada

Mo1962 Post-Market Analysis of the Use and Effectiveness of GTA-446, a Blood Test That Identifies Persons With Elevated Colorectal Cancer Risk, in Ontario, Canada

Familial colorectal cancer risk by subsite of primary cancer: a population-based study in Utah.

Familial occurrence is common in colorectal cancer (CRC), but whether this increased familial risk differs by colonic subsite of the index patients CRC is not well understood. To quantify the risk of CRC in first-degree (FDR), second-degree (SDR) and first cousin (FC) relatives of individuals with CRC, stratified by subsite in the colorectum and age at diagnosis. Colorectal cancers diagnosed between 1980 and 2010 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age and gender-matched CRC-free controls were selected to form the comparison group for determining CRC risk in relatives using Cox regression analysis. Of the 18,208 index patients diagnosed with CRC, 6584 (36.2%) were located in the proximal colon, 5986 (32.9%) in the distal colon and 5638 (31%) in the rectum. The elevated risk of CRC in relatives was similar in analysis stratified for CRC colorectal subsites in the index cases. FDR had similarly elevated risk of all site CRC, whether the index patient had cancer in the proximal colon [hazards ratio (HR): 1.85; 95% CI: 1.70-2.02], distal colon (HR: 1.90; 95% CI: 1.73-2.08) or rectum (HR: 1.83; 95% CI: 1.66-2.02) compared to relatives of controls. This risk was consistently greater for FDR when cases developed CRC below the age of 60 years. Relatives of CRC patients have a similarly elevated risk of CRC regardless of colonic tumour subsite in the index patient, and it is greatest for relatives of younger age index cases.

XRCC3 Thr241Met gene polymorphism and risk of colorectal cancer in Kashmir: a case control study.

XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC (p≤0.05). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p=0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.

Ten-year incidence of colorectal cancer following a negative screening sigmoidoscopy: an update from the Colorectal Cancer Prevention (CoCaP) programme

ObjectiveTo examine the rates of colorectal cancer (CRC) following a negative screening sigmoidoscopy.DesignCohort study.SettingAn integrated healthcare delivery organisation in California, USA.Participants72 483 men and women aged 50 years and above...

Alcohol, one-carbon nutrient intake, and risk of colorectal cancer according to tumor methylation level of IGF2 differentially methylated region

Although a higher consumption of alcohol, which is a methyl-group antagonist, was previously associated with colorectal cancer risk, mechanisms remain poorly understood. We hypothesized that excess alcohol consumption might increase risk of colorectal carcinoma with hypomethylation of insulin-like growth factor 2 (IGF2) differentially methylated region-0 (DMR0), which was previously associated with a worse prognosis. With the use of a molecular pathologic epidemiology database in 2 prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association between alcohol intake and incident colorectal cancer according to the tumor methylation level of IGF2 DMR0. Duplication-method Cox proportional cause-specific hazards regression for competing risk data were used to compute HRs and 95% CIs. In addition, we investigated intakes of vitamin B-6, vitamin B-12, methionine, and folate as exposures. During 3,206,985 person-years of follow-up, we identified 993 rectal and colon cancer cases with an available tumor DNA methylation status. Compared with no alcohol consumption, the consumption of ≥15 g alcohol/d was associated with elevated risk of colorectal cancer with lower levels of IGF2 DMR0 methylation [within the first and second quartiles: HRs of 1.55 (95% CI: 1.08, 2.24) and 2.11 (95% CI: 1.44, 3.07), respectively]. By contrast, alcohol consumption was not associated with cancer with higher levels of IGF2 DMR0 methylation. The association between alcohol and cancer risk differed significantly by IGF2 DMR0 methylation level (P-heterogeneity = 0.006). The association of vitamin B-6, vitamin B-12, and folate intakes with cancer risk did not significantly differ according to IGF2 DMR0 methylation level (P-heterogeneity > 0.2). Higher alcohol consumption was associated with risk of colorectal cancer with IGF2 DMR0 hypomethylation but not risk of cancer with high-level IGF2 DMR0 methylation. The association between alcohol intake and colorectal cancer risk may differ by tumor epigenetic features.

Smoking Is Associated With an Increased Risk of Adenomas in Patients at High Risk for Colorectal Cancer

Introduction: Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States. Adenoma removal has been shown to reduce deaths from CRC. Although smoking has been associated with an increased risk of CRC, smoking status is not included in algorithms that guide colonoscopy for CRC screening and surveillance. This study evaluated the impact of smoking on adenoma detection in patients who are at elevated risk for CRC. Methods: Reports of consecutive colonoscopies performed at an urban university hospital during a 6-month period were reviewed and their indications and results noted. Colonoscopies performed for screening of elevated risk patients and/or surveillance indications were included. Elevated risk was defined as personal or family history of CRC or polyp, inflammatory bowel disease (IBD), or “high risk for CRC” as the stated indication. Patients’ demographics, family history, and smoking history were collected. Maintaining patient confidentiality, a database was created using Microsoft Excel. Statistical analysis was performed using Fisher’s exact test with significance set at p<0.05. The study was approved by the university IRB. Results: There were 589 screening or surveillance colonoscopies for elevated-risk patients. Among them, 373 never smoked and 216 had. Adenoma were detected in 123 elevated-risk patients who had smoked (56.9%) and 166 (44.5%) of the never smokers (p=0.0037). Family history was the sole risk factor for 79 patients deemed high risk (20 male, 59 female), and adenomas were discovered in 25 (31.6%). Colonoscopies were performed in 421 patients with history of polyp; 243 (57.7%) had adenomas. There were 56 IBD patients and 3 (5.4%) had adenomas. Among elevated CRC risk patients, smoking was associated with a higher adenoma detection rate than was IBD (p<0.001), and family history of CRC (p=0.001), but not personal history of colon polyp (p=0.8659). Conclusion: Adenoma detection and removal decreases CRC deaths. Personal and family history of CRC or adenoma and IBD are recognized risk factors and influence the recommended age of onset and interval of screening colonoscopy. In this study, there was a significantly higher adenoma detection rate in smokers at increased risk of CRC. The rate of adenoma detection was significantly higher in smokers than in those with a family history of CRC or IBD. The patient’s smoking status should be considered when individualizing recommendations for CRC screening and surveillance, particularly in patients who are at high risk.

Abstract 2193: Colorectal cancer risk associated with alcohol intake is modified by common genetic variants in one-carbon metabolism: the Multiethnic Cohort Study

Abstract Background: Epidemiologic studies have observed that higher alcohol intake is associated with an increased risk of colorectal cancer and that the effects of alcohol may vary by common genetic polymorphisms in one-carbon metabolism enzymes, most notably MTHFR. Experimental studies demonstrated alcohol may impair the activity of some of the enzymes involved in the pathway. We examined common functional genetic variants in key one-carbon metabolism enzymes and their interactions with alcohol intake in association with the risk of colorectal cancer in a prospective study. Materials and Methods: We conducted a study within the Multiethnic Cohort on 1,670 incident colorectal cancer (932 male, 738 female) cases and 2,532 controls that were frequency-matched based on baseline age (45-75), sex and race/ethnicity (African American, white, Japanese American, Latino and Native Hawaiian). Alcohol intake was estimated from a self-administered food frequency questionnaire. Reported functional variants were genotyped in BHMT, CBS, CHDH, MTHFD1, MTHFR, MTR, MTRR, PEMT, and TCN2, using TaqMan assays. Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations adjusted for age, sex, and race/ethnicity. Results: In the nested case-control subset, as in the entire cohort, alcohol intake was associated with an elevated risk of colorectal cancer [ORs for &amp;lt;7g or 0.5 drink/day and ≥ 7g/day intake compared to non-drinking were 1.16 (95% CI: 0.99, 1.35) and 1.30 (1.11, 1.54), respectively; p-trend=0.001]. We found an association of colorectal cancer with rs1801133 in MTHFR [OR=0.81 (0.66, 0.99) for TT vs. CC/CT], as reported earlier, and also with rs1801131 [MTHFR; OR=1.36 (1.02, 1.86) for CC vs. AA/AC] and rs12676 [CHDH; OR=0.84 (0.70, 0.99) for AC/CC vs. AA]. There was a significant interaction between alcohol intake and genetic variants rs1801133 (p-interaction=0.02) and rs1801131 (p-interaction=0.04) in MTHFR, rs12676 (CHDH; p-interaction=0.0002), and rs234706 (CBS; p-interaction=0.002). Alcohol-associated colorectal cancer risk increases were observed only among individuals with the following genotypes: rs1801133 TT [ORs for &amp;lt;7g/day and ≥ 7g/day intake compared to non-drinking: 1.78 (1.11, 2.85), 2.11 (1.25, 3.56)], rs1801131 AA [ORs=1.18 (1.00, 1.30), 1.35 (1.14, 1.59)], rs12676 AA [ORs=1.23 (1.03, 1.47), 1.44 (1.20, 1.74) and rs234706 GG [ORs=1.21 (1.00, 1.46), 1.48 (1.21, 1.81)]. Conclusions: Our findings provide further support that alcohol intake may increase the risk of colorectal cancer in part through its antagonistic effects on one-carbon metabolism, especially among carriers of susceptibility genotypes for key enzymes. Citation Format: Unhee Lim, Lynne R. Wilkens, Maarit Tiirikainen, Carol J. Boushey, Laurence N. Kolonel, Loic Le Marchand. Colorectal cancer risk associated with alcohol intake is modified by common genetic variants in one-carbon metabolism: the Multiethnic Cohort Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2193. doi:10.1158/1538-7445.AM2014-2193

Risk of colorectal cancer and adenomas in the families of patients with adenomas: A population‐based study in Utah

Guidelines recommend that individuals with a first-degree relative (FDR) diagnosed with colorectal cancer (CRC) or advanced adenoma before age 60 years should undergo colonoscopy starting at age 40 years. The authors quantified the risk of adenomas and CRC in FDRs, second-degree relatives (SDRs), and third-degree relatives (TDRs) of patients diagnosed with adenomas and advanced adenomas. A population-based, retrospective, case-control study was performed of residents of the state of Utah aged 50 years to 80 years who underwent colonoscopy between 1995 and 2009 at Intermountain Healthcare or the University of Utah. Controls were selected from the population of colonoscopy patients who were free of adenomas or CRC and matched to each case based on sex and birth year. Colonoscopy results were linked with cancer and pedigree information from the Utah Population Database to investigate the familial aggregation of adenomas and CRC using Cox regression analysis. The unit of analysis was the relatives of cases and controls. Of 126,936 patients who underwent colonoscopy, 43,189 had adenomas and 5563 had advanced adenomas and defined the case population. An elevated risk of CRC was found in FDRs (relative risk [RR], 1.35; 95% confidence interval [95% CI], 1.25-1.46), SDRs (RR, 1.15; 95% CI, 1.07-1.23) of adenoma cases, and in FDRs of advanced adenoma cases (RR, 1.68; 95% CI, 1.29-2.18) compared with controls. Approximately 10% of CRCs diagnosed in relatives would have been missed if the current screening guidelines were strictly adhered to. Relatives of colonoscopy patients with adenomas and advanced adenomas appear to have a significantly elevated risk of developing colorectal neoplasia. These data should be considered when establishing CRC screening guidelines for individuals and their families.

Fatty Acid Synthase in the Endoscopically Normal Rectal Mucosa as Marker for Obesity-related Colorectal Cancer (CRC) Risk: Gender-specific Implications: Presidential Poster

Purpose: The clinical implications of the profound biological differences in CRC between women and men are largely underappreciated. Our group has noted a “gender paradox” for advanced adenomas and CRC in women and men which may have potential ramifications for screening (JAMA 2009;302:1696-7). We have noted that changes in field carcinogenesis (reviewed in Gastroenterology 2011;140:35-41) may also be gender specific (Cancer Prev Res 2010;3:844-51). With regards to risk factor, the role of obesity is becoming increasingly dominant. Emerging data indicates that men appear to be disproportionately impacted versus women (reviewed by Bardou, et al. Gut 2013;62:933-47). Understanding which obese patients are at elevated risk of CRC is critical. We, therefore, evaluated fatty acid synthase (FASN), a protein implicated in the “lipogenic switch” in early colon carcinogenesis. FASN has been implicated in frank CRCs but little is known about the role of FASN in early events such as field carcinogenesis or its gender predilection. Methods: Two biopsies were obtained from endoscopically normal rectum from 103 patients undergoing screening colonoscopy. Subjects were dichotomized into non-obese and obese using a BMI of 30 as a cut point. Biopsies were subjected to real time PCR analysis for FASN and normalized with beta-actin. Results: Obese patients had an induction of FASN when compared to corresponding non-obese subjects (controls 50%, adenoma-harboring 29%, p<0.05). Rectal FASN was highly overexpressed in adenoma patients versus controls and this was a much more dramatic effect in men than women (see Figure). ANCOVA analysis suggested no significant confounding with age, adenoma size, smoking status, etc.FigureConclusion: We report herein, for the first time, alterations in FASN in patients harboring adenomas. This was accentuated in obese patients suggesting a potential molecular link between obesity and colonic neoplasia. Importantly, the effect was more marked in males than females, consonant with the obesity-CRC epidemiology. These insights into the molecular pathogenesis of obesity-related CRC suggest a role of this “lipogenic switch” in gender differences in CRC. Furthermore, this may be a “druggable” target against obesity-induced CRC and also provide a biomarker for determining at risk patients, thus enabling personalizing CRC prevention strategies.

Risk of colorectal cancer and endoscopic screening in families of patients with hereditary nonpolyposis syndrome of colorectal cancer.

e12543 Background: Relatives of patients with hereditary nonpolyposis colorectal cancer (HNPCC) have an elevated risk of colorectal cancer (CRC) and adenomas. To determine the efficacy of endoscopic screening among relatives of patients with HNPCC syndrome. Methods: 50 relatives of the first and 17 relatives of the second-degree relatives of 127 families of patients with HNPCC syndrome was subjected to endoscopic screening (colonoscopy). Results: The analysis of cancer register database of families, which includes clinical and genealogical information about 1,505 patients with colorectal cancer (CRC) and 407 with the primary multiple malignant neoplasms (PMMN), found 127 (6.6%) families, which are consistent with Amsterdam criteria of HNPCC. Among the 1057 first-degree relatives malignancies were detected in 238 (22.5±2.7%). The CRC among of the first degree relatives of patients with HNPCC syndrome was identified in 118 (11.2±2.9%), which is 20 times the population frequencies (0.56±0.004%) (p&lt;0.001). The frequency of aggregation of PMMN and adenomas of the colon was 1.8±3.1% (19) è 0.6% (6), respectively. Prevalence of PMMN in the general population is 0.009±0.0005%, and adenomas - 4.7±1.4%. From 809 of first degree relatives 50 were available for the survey, and from the 924 second degree relatives - 20. The endoscopic screening of first degree relatives found the presence of different pathology in 35(60.0%±8.3%) surveyed persons, including CRC – at 19(38.0±11.4%) (p&lt;0.01), primary multiple colorectal cancer – at 6(12.0±14.5%), adenomas - at 5(10.0%). Among the surveyed second degree relatives the pathology was identified at 8(40±18.5%), primary multiple colorectal cancer at 3(15.0%), and adenomas of the colon – at 5(25%). Conclusions: Colonoscopy is an effective method for identifying malignant and benign tumors of the colon at relatives in the families of patients with HNPCC syndrome. A high percentage of cancer detected in these families need to refine the survey mode in order to identify early forms of cancer and its secondary prevention.

Association between XRCC3 Thr241Met polymorphism and colorectal cancer risk

The x-ray repair cross-complementing group 3 (XRCC3), a member of DNA repair genes, plays a critical role in the maintenance of genome stability by homologous recombination repair for DNA double-strand breaks. The polymorphism of XRCC3 Thr241Met has been indicated to be involved in the development of some cancers, but previous individual studies on the association between XRCC3 Thr241Met polymorphism and colorectal cancer (CRC) risk have yielded conflicting and inconclusive results. To shed some light on the contradictory findings and improve our understanding of the pathogenesis of CRC, we carried out this updated meta-analysis by pooling all available publications. Databases including PubMed, Embase, Web of Science and China National Knowledge Infrastructure were searched for relevant publications. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to estimate the strength of the association between XRCC3 Thr241Met polymorphism and CRC risk. A total of 15 case-control studies involving 4,475 cases and 6,373 controls were included. Overall, the pooled ORs for the meta-analysis of total included studies showed no statistically significant association of XRCC3 Thr241Met polymorphism with CRC risk in any genetic model (ORMet allele vs. Thr allele=1.17, 95 % CI 0.97-1.42, P OR=0.102; ORMetMet vs. ThrThr =1.32, 95 % CI 0.93-1.87, P OR=0.121; ORThrMet vs. ThrThr =1.17, 95 % CI 0.94-1.45, P OR=0.150; ORMetMet + ThrMet vs. ThrThr =1.20, 95 % CI 0.96-1.51, P OR=0.114; ORMetMet vs. ThrThr + ThrMet =1.37, 95 % CI 0.98-1.93, P OR=0.065). However, in subgroup analyses stratified by source of controls and ethnicity, the XRCC3 Thr241Met polymorphism was associated with an elevated risk of CRC in the hospital-based case-control studies and the Asian population. Sensitivity analysis indicated that the findings were unlikely due to chance. This meta-analysis suggests that the XRCC3 Thr241Met polymorphism may modify the risk of CRC, particularly in Asians.

Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: A case control study

The aim of this study was to investigate the role of the XRCC1 Arg399Gln polymorphism in the susceptibility of a Kashmiri population to colorectal cancer (CRC). We investigated the genotype distribution of the XRCC1 gene in 130 CRC cases in comparison with that of 150 healthy subjects. There was no direct significant association between the XRCC1 genotypes and CRC; however, the Arg/Gln genotype was associated with an elevated risk of CRC (OR>1.47) and the Gln/Gln variant genotype was associated with an increased risk of CRC in various clinicopathological parameters. This study suggests that the XRCC1 polymorphism is associated with an increased risk of CRC.

Prospective study of family history and colorectal cancer risk by tumor LINE-1 methylation level.

Beyond known familial colorectal cancer (CRC) syndromes, the mechanisms underlying the elevated CRC risk associated with CRC family history remain largely unknown. A recent retrospective study suggests familial clustering of CRC with hypomethylation in long interspersed nucleotide element 1 (LINE-1). We tested the hypothesis that CRC family history might confer a higher risk of LINE-1 methylation-low CRC. Using the Nurses' Health Study and the Health Professionals Follow-up Study, we prospectively examined the association between CRC family history and the risk of rectal and colon cancer (N = 1224) according to tumor LINE-1 methylation level by duplication method Cox proportional hazards regression. We examined microsatellite instability (MSI) status to exclude the influence of Lynch syndrome. All statistical tests were two-sided. The association between CRC family history and non-MSI CRC risk differed statistically significantly by LINE-1 methylation level (P (heterogeneity) = .02). CRC family history was associated with a statistically significantly higher risk of LINE-1 methylation-low non-MSI cancer (multivariable hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.19 to 2.38 for 1 vs 0 first-degree relatives with CRC; multivariable HR = 3.48, 95% CI = 1.59 to 7.6 for ≥2 vs 0 first-degree relatives with CRC; P (trend) < .001). In contrast, CRC family history was not statistically significantly associated with LINE-1 methylation-high non-MSI cancer (P (trend) = .35). This molecular pathological epidemiology study shows that CRC family history is associated with a higher risk of LINE-1 methylation-low CRC, suggesting previously unrecognized heritable predisposition to epigenetic alterations. Additional studies are needed to evaluate tumor LINE-1 methylation as a molecular biomarker for familial cancer risk assessment.

Abstract CN03-01: Predictors of change in colorectal cancer screening decision stage among participants in a randomized, controlled trial of genetic and environmental risk assessment

Abstract Purpose. This report presents findings from a randomized, controlled trial of colorectal cancer (CRC) genetic and environmental risk assessment (GERA). Predictors of positive change in CRC screening decision stage (SDS) were identified among participants who completed a baseline and follow-up survey. Methods. A total of 493 primary care patients who were 50 to 79 years of age, were eligible for CRC screening were randomized to a GERA Group (n=328) or a usual care Control Group (n=165). GERA Group participants underwent decision counseling about GERA, had a blood draw to assess CRC risk, and received risk feedback (modestly-elevated or average risk) based on the combined presence of SNPs 677C&amp;gt;T and/or 1298A&amp;gt;C of the methylenetetrahydrofolate reductase (MTHFR) gene and serum folate level. Participants received a CRC screening kit and completed a follow-up telephone survey. Univariable analyses and multivariable regression were performed to determine if baseline screening sociodemographic and lifestyle factors, knowledge, psychosocial factors, stress about CRC, SDS, and risk status predicted self-reported change in SDS. Results. Participants were: female (56%), white (61%), 50 to 59 years of age (66%), &amp;gt; high school education (71%), and married (55%). Overall, SDS was as follows: decided against (1%), undecided (11%), and decided to do (87%) screening. 38% of participants exhibited a positive change in SDS to a higher decision stage, including actual screening. Positive SDS change by study group was: GERA Group (39%) and Control Group (34%). Multivariable analyses for all participants showed that knowledge was a positive predictor (p=0.006) of SDS change, as were lower CRC stress and lower SDS (p=0.023 and p&amp;lt;0.001, respectively). 12% of GERA Group participants had an elevated risk for CRC. Positive SDS change in the GERA Group by risk status was: elevated risk (36%) and average risk (42%). In the GERA Group, knowledge was a positive, nonsignificant predictor (p=0.107) of SDS change, while lower CRC stress and lower SDS were significant positive predictors (p=0.038 and p&amp;lt;0.001, respectively). Conclusion. Exposure to GERA and feedback indicating modestly-elevated risk influenced change in SDS among participants who had greater knowledge about CRC screening, reported lower CRC stress, or had decided against about or were uncertain about CRC screening. Citation Format: Ronald E. Myers, Sharon Manne, Karen Ruth, James Cocroft, Randa Sifri, Barry Ziring, David Weinberg. Predictors of change in colorectal cancer screening decision stage among participants in a randomized, controlled trial of genetic and environmental risk assessment. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN03-01.

Elevated Risk of Colorectal Cancer in Relatives of Patients with Colorectal Cancer: A Population-Based Study in Utah: ACG Colorectal Cancer Prevention Award

Elevated Risk of Colorectal Cancer in Relatives of Patients with Colorectal Cancer: A Population-Based Study in Utah: ACG Colorectal Cancer Prevention Award