Risk Of Colorectal Cancer Death Research Articles

Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death

The fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, but evidence of its effectiveness is limited. To evaluate whether FIT screening is associated with a lower risk of dying from CRC overall, according to cancer location, and within demographic groups. This nested case-control study in a cohort of screening-eligible people was conducted in 2 large, integrated health systems of racially, ethnically, and socioeconomically diverse members with long-term programs of mailed FIT screening outreach. Eligible participants included people aged 52 to 85 years who died from colorectal adenocarcinoma between 2011 and 2017 (cases); cases were matched in a 1:8 ratio based on age, sex, health-plan membership duration, and geographic area to randomly selected persons who were alive and CRC-free on case's diagnosis date (controls). Data analysis was conducted from January 2002 to December 2017. Completing 1 or more FIT screenings in the 5-year period prior to the CRC diagnosis date among cases or the corresponding date among controls; in secondary analyses, 2- to 10-year intervals were evaluated. The primary study outcome was CRC death overall and by tumor location. Secondary analyses were performed to assess CRC death by race and ethnicity. From a cohort of 2 127 128 people, a total of 10 711 participants (3529 aged 60-69 years [32.9%]; 5587 male [52.1%] and 5124 female [47.8%]; 1254 non-Hispanic Asian [11.7%]; 973 non-Hispanic Black [9.1%]; 1929 Hispanic or Latino [18.0%]; 6345 non-Hispanic White [59.2%]) was identified, including 1103 cases and 9608 controls. Among controls during the 10-year period prior to the reference date, 6101 (63.5%) completed 1 or more FITs with a cumulative 12.6% positivity rate (768 controls), of whom 610 (79.4%) had a colonoscopy within 1 year. During the 5-year period, 494 cases (44.8%) and 5345 controls (55.6%) completed 1 or more FITs. In regression analysis, completing 1 or more FIT screening was associated with a 33% lower risk of death from CRC (adjusted odds ratio [aOR], 0.67; 95% CI, 0.59-0.76) and 42% lower risk in the left colon and rectum (aOR, 0.58; 95% CI, 0.48-0.71). There was no association with right colon cancers (aOR, 0.83; 95% CI, 0.69-1.01) but the difference in the estimates between the right colon and left colon or rectum was statistically significant (P = .01). FIT screening was associated with lower CRC mortality risk among non-Hispanic Asian (aOR, 0.37; 95% CI, 0.23-0.59), non-Hispanic Black (aOR, 0.58; 95% CI, 0.39-0.85) and non-Hispanic White individuals (aOR, 0.70; 95% CI, 0.57-0.86) (P for homogeneity = .04 for homogeneity). In this nested case-control study, completing FIT was associated with a lower risk of overall death from CRC, particularly in the left colon, and the associations were observed across racial and ethnic groups. These findings support the use of FIT in population-based screening strategies.

Faecal haemoglobin concentration predicts all-cause mortality

BackgroundPopulation-based screening for colorectal cancer by a faecal immunochemical test (FIT) is recommended by the European Union. Detectable faecal haemoglobin can indicate colorectal neoplasia as well as other conditions. A positive FIT predicts an increased risk of death from colorectal cancer but might also predict an increased risk of all-cause mortality. MethodsA cohort of screening participants was followed using the Danish National Register of Causes of Death. Data were retrieved from the Danish Colorectal Cancer Screening Database supplemented with FIT concentrations. Colorectal cancer specific and all-cause mortality were compared between FIT concentration groups using multivariate cox proportional hazards regression models. FindingsIn 444,910 Danes invited for the screening program, 25,234 (5·7%) died during a mean follow-up of 56·5 months. Colorectal cancer caused 1120 deaths. The risk of colorectal cancer death increased with the increasing FIT concentration. The hazard ratios ranged from 2·6 to 25·9 compared to individuals with FIT concentrations <4 μg hb/g faeces. Causes other than colorectal cancer caused 24,114 deaths. The risk of all-cause death increased with the increasing FIT concentration, with the hazard ratios ranging from 1·6 to 5·3 compared to individuals with FIT concentrations <4 μg hb/g faeces. InterpretationThe risk of colorectal cancer mortality increased with the increasing FIT concentrations even for FIT concentrations considered negative in all European screening programs. The risk of all-cause mortality was also increased for individuals with detectable faecal blood. For colorectal cancer specific mortality and all-cause mortality, the risk was increased at the FIT concentrations as low as 4–9 μg hb/g faeces. FundingThe study was funded by the Odense University Hospital grants A3610 and A2359.

Perceived Importance of the Benefits and Harms of Colorectal Cancer Screening: A Best-Worst Scaling Study

ObjectivesTo elicit the relative importance of the benefits and harms of colorectal cancer (CRC) screening among potential screening participants in the Dutch population. MethodsIn a consensus meeting with 11 experts, risk reduction of CRC and CRC deaths (benefits) and complications from colonoscopy, stress of receiving positive fecal immunological test (FIT) results, as well as false-positive and false-negative FIT results (harms) were selected as determinant end points to consider during decision making. We conducted an online best-worst scaling survey among adults aged 55 to 75 years from the Dutch Health Care Consumer Panel of The Netherlands Institute for Health Services Research to elicit preference values for these outcomes. The preference values were estimated using conditional logit regression. ResultsOf 265 participants, 234 (89%) had ever participated in CRC screening. Compared with the stress of receiving a positive FIT result, the outcome perceived most important was the risk of CRC death (odds ratio [OR] 4.5; 95% confidence interval [CI] 3.9-5.1), followed by risk of CRC (OR 4.1; 95% CI 3.6-4.7), a false-negative FIT result (OR 3.1; 95% CI 2.7-3.5), colonoscopy complications (OR 1.6; 95% CI 1.4-1.8), and a false-positive FIT result (OR 1.4; 95% CI 1.3-1.6). The magnitude of these differences in perceived importance varied according to age, educational level, ethnic background, and whether the individual had previously participated in CRC screening. ConclusionDutch men and women eligible for FIT-based CRC screening perceive the benefits of screening to be more important than the harms.

Colorectal cancer in elderly-onset inflammatory bowel disease: a 1969-2017 Scandinavian register-based cohort study.

SummaryBackgroundPrevious research indicates that the increased relative risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) is limited to young‐onset IBD.AimTo estimate risks of incident CRC and death from CRC in elderly‐onset IBDMethodsPatients diagnosed with IBD at age ≥ 60 years between 1969 and 2017 were identified using Danish and Swedish National Patient Registers and histopathology data. We linked data to Cancer and Causes of Death Registers and used Cox regression to estimate hazard ratios (HRs) for CRC diagnosis and death compared to matched (by sex, age, and region) IBD‐free individuals.ResultsAmong 7869 patients with Crohn's disease followed for 54,220 person‐years, and 21,224 patients with ulcerative colitis (UC) followed for 142,635 person‐years, 2.10% and 1.90% were diagnosed with CRC, compared to 2.26% and 2.34% of reference individuals (median follow‐up 6 and 7 years). The incidence of CRC was elevated during the first year after IBD diagnosis: 4.36 (95% CI = 3.33–5.71) in Crohn's disease and 2.48 (95% CI = 2.03–3.02) in UC, but decreased after the first year of follow‐up: 0.69 (95% CI = 0.56–0.86) and 0.78 (95% CI = 0.69–0.88). Once diagnosed with CRC, the risk of CRC death was similar for IBD patients and the general population.ConclusionThe excess risk of CRC in elderly‐onset IBD was probably due to bias and not observed beyond the first year. From 2010, the HR for CRC diagnosis more than 1 year after initial IBD diagnosis was lower than in the largely unscreened reference population, supporting the benefit of endoscopic screening and surveillance in patients with IBD.

Long-term colorectal cancer incidence and mortality after adenoma removal in women and men.

Women and men with colorectal adenomas are at increased risk of colorectal cancer and colonoscopic surveillance is recommended. However, the long-term cancer risk remains unknown. To investigate colorectal cancer incidence and mortality after adenoma removal in women and men METHODS: We identified all individuals who had adenomas removed in Norway from 1993 to 2007, with follow-up through 2018. We calculated standardized incidence ratios (SIR) and incidence-based mortality ratios (SMR) with 95% confidence intervals (CI) for colorectal cancer in women and men using the female and male population for comparison. We defined high-risk adenomas as ≥2 adenomas, villous component, or high-grade dysplasia. The cohort comprised 40293 individuals. During median follow-up of 13.0years, 1079 women (5.5%) and 866 men (4.2%) developed colorectal cancer; 328 women (1.7%) and 275 men (1.3%) died of colorectal cancer. Colorectal cancer incidence was more increased in women (SIR 1.64, 95% CI 1.54-1.74) than in men (SIR 1.12, 95% CI 1.05-1.19). Colorectal cancer mortality was increased in women (SMR 1.13, 95% CI 1.02-1.26) and reduced in men (SMR 0.79, 95% CI 0.71-0.89). Women with high-risk adenomas had an increased risk of colorectal cancer death (SMR 1.37, 95% CI 1.19-1.57); women with low-risk adenomas (SMR 0.90, 95% CI 0.76-1.07) and men with high-risk adenomas had a similar risk (SMR 0.89, 95% CI 0.76-1.04), while men with low-risk adenomas had reduced risk (SMR 0.70, 95% CI 0.59-0.84). After adenoma removal, women had an increased risk of colorectal cancer death, while men had reduced risk, compared to the general female and male populations. Sex-specific surveillance recommendations after adenoma removal should be considered.

633Poorly controlled diabetes is a predictor of colorectal cancer survival

Abstract Background Epidemiological studies have shown diabetes associated with increased risk of colorectal cancer. This study investigates the impact of a pre-cancer diabetes-related hospitalization record on colorectal cancer survival. Methods A retrospective cohort of 13190 colorectal cancer patients recorded on the South Australian Cancer Registry in 2003-2013 were examined. Diabetes-related hospitalization histories were obtained using linked inpatient data. Colorectal cancer deaths were available for 2003-2013. The association of survival from colorectal cancer with diabetes-related hospitalization history was assessed using competing risk analysis, adjusting for sociodemographic factors and cancer stage at diagnosis. Results 2765 patients with colorectal cancer (26.5%) had a history of hospital admission for diabetic complications, the most common being multiple complications (32%), followed by kidney and eye complications. The 5- and 10-year cancer survival probabilities were 63% and 56% in those with a diabetes complication history, significantly lower than 66% and 60% for patients without these complications (adjusted sub hazard ratio 1.11, 95% CI 1.02-1.20). Risk of colorectal cancer death was lower when theses diabetes-related hospitalizations were earlier than the year of cancer diagnosis - i.e., adjusted SHR 0.80, 95% CI 0.66-0.97 for 3-5 and 0.76, 95% CI 0.59-0.98 for 6+ years before the cancer diagnosis compared with same-year hospitalizations. Conclusions Colorectal cancer patients with a history of diabetes-related hospitalization have poorer survival, particularly if these hospitalizations were in the same year as the cancer diagnosis. Key messages Poorly controlled diabetes histories predict increased risk of colorectal cancer mortality.

Development and user-testing of a brief decision aid for aspirin as a preventive approach alongside colorectal cancer screening

BackgroundSeveral epidemiological and cohort studies suggest that regular low-dose aspirin use independently reduces the long-term incidence and risk of colorectal cancer deaths by approximately 20%. However, there are also risks to aspirin use, mainly gastrointestinal bleeding and haemorrhagic stroke. Making informed decisions depends on the ability to understand and weigh up benefits and risks of available options. A decision aid to support people to consider aspirin therapy alongside participation in the NHS bowel cancer screening programme may have an additional impact on colorectal cancer prevention. This study aims to develop and user-test a brief decision aid about aspirin to enable informed decision-making for colorectal screening-eligible members of the public.MethodsWe undertook a qualitative study to develop an aspirin decision aid leaflet to support bowel screening responders in deciding whether to take aspirin to reduce their risk of colorectal cancer. The iterative development process involved two focus groups with public members aged 60–74 years (n = 14) and interviews with clinicians (n = 10). Interviews (n = 11) were used to evaluate its utility for decision-making. Analysis was conducted using a framework approach.ResultsOverall, participants found the decision aid acceptable and useful to facilitate decision-making. They expressed a need for individualised risk information, more detail about the potential risks of aspirin, and preferred risk information presented in pictograms when offered different options. Implementation pathways were discussed, including the possibility of involving different clinicians in the process such as GPs and/or community pharmacists. A range of potentially effective timepoints for sending out the decision aid were identified.ConclusionAn acceptable and usable decision aid was developed to support decisions about aspirin use to prevent colorectal cancer.

Television Viewing Time and the Risk of Colorectal Cancer Mortality among Japanese Population: The JACC Study.

PurposeSedentary behavior attributes to the increased risk of some cancers and all-cause mortality. The evidence is limited for the association between television (TV) viewing time, a major sedentary behavior, and risk of colorectal cancer death. We aimed to examine this association in Japanese population.Materials and MethodsA prospective cohort study encompassed of 90,834 men and women aged 40–79 years with no prior history of colorectal cancer who completed a self-administered food frequency questionnaire, and provided their TV viewing information. The participants were followed-up from 1988–1990 to the end of 2009. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazard regression for risk of colorectal cancer mortality according to TV viewing time.ResultsDuring the median 19.1-year follow-up period, we documented 749 (385 men and 364 women) colorectal cancer deaths. The multivariable-adjusted HRs for mortality from colorectal cancer were 1.11 (0.88–1.41) for 1.5 to < 3 hr/day, 1.14 (0.91–1.42) for 3 to < 4.5 hr/day and 1.33 (1.02–1.73) for ≥ 4.5 hr/day in comparison to < 1.5 hr/day TV watching; p-trend=0.038, and that for 1-hour increment in TV viewing time was 1.06 (1.01–1.11). Moreover, the multivariable-adjusted HR (95% CI) of colon cancer for 1-hour increment in TV viewing time was 1.07 (1.02–1.13). Age, body mass index, and level of leisure-physical activity did not show significant effect modifications on the observed associations.ConclusionTV viewing time is associated with the increased risk of colorectal cancer mortality among Japanese population, more specifically colon rather than rectal cancer.

Post-diagnosis dietary insulinemic potential and survival outcomes among colorectal cancer patients

BackgroundThe empirical dietary index for hyperinsulinemia (EDIH) score is a validated food-based dietary score that assesses the ability of whole-food diets to predict plasma c-peptide concentrations. Although the EDIH has been extensively applied and found to be predictive of risk of developing major chronic diseases, its influence on cancer survival has not been evaluated. We applied the EDIH score in a large cohort of colorectal cancer patients to assess the insulinemic potential of their dietary patterns after diagnosis and determine its influence on survival outcomes.MethodsWe calculated EDIH scores to assess the insulinemic potential of post-diagnosis dietary patterns and examined survival outcomes in a sample of 1718 stage I-III colorectal cancer patients in the Nurses’ Health Study and Health Professionals Follow-up Study cohorts. Multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific mortality and all-cause mortality. We also examined the influence of change in diet from pre- to post-diagnosis period, on mortality.ResultsDuring a median follow-up of 9.9 years, there were 1008 deaths, which included 272 colorectal cancer-specific deaths (27%). In the multivariable-adjusted analyses, colorectal cancer patients in the highest compared to lowest EDIH quintile, had a 66% greater risk of dying from colorectal cancer: HR, 1.66; 95% CI, 1.03, 2.69; and a 24% greater risk of all-cause death: HR, 1.24; 95%CI, 0.97, 1.58. Compared to patients who consumed low insulinemic diets from pre- to post-diagnosis period, patients who persistently consumed hyperinsulinemic diets were at higher risk of colorectal cancer death (HR,1.51; 95%CI, 0.98, 2.32) and all-cause death (HR, 1.31; 95%CI, 1.04, 2.64).ConclusionOur findings suggest that a hyperinsulinemic dietary pattern after diagnosis of colorectal cancer is associated with poorer survival. Interventions with dietary patterns to reduce insulinemic activity and impact survivorship are warranted.

Abstract 2357: Lipid-lowering drug use, duration of use, and age at first use is associated with a lower risk of colorectal cancer mortality in men and women in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract Background: While lipid-lowering drugs, particularly statins, are associated with a modestly reduced risk of developing colorectal cancer (CRC), the association of lipid-lowering drug use, duration of use, and age at first use with CRC mortality in men and women without the diagnosis at baseline, has not been well studied. Further, whether associations are similar across race is unknown. Thus, we aimed to characterize the association between lipid-lowering drug use and CRC mortality in men and women and by race. We classified lipid-lowering drug use in a time-dependent manner as current use, duration of use, and age at first use. Methods: We conducted a prospective cohort study of 14,428 cancer-free men and women attending visit 2 (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) Study. Death from CRC was ascertained from the underlying cause on death certificates. Follow-up began at visit 2 and ended at date of death or 12/31/2015, whichever came first. There were 384 incident CRC cases and 144 deaths in 290,249 person-years. Cox regression was used to estimate relative hazards (HR) and 95% confidence intervals (CI) for CRC incidence and death adjusting for age, sex, education, race and field center, BMI, smoking status and pack years, alcohol use, red and processed meat consumption, aspirin use, and family history of any cancer and family history of CRC overall and by gender and race. Current lipid-lowering medication use, duration of use (&amp;lt;15 years, ≥15 years), and age at first use (&amp;lt;50, 50-59, 60-69, and ≥70 years of age) were modeled as time-dependent variables. Results: Mean age was 57 years and mean BMI was 28.1 kg/m2; 54.9% were women and 27.9% were Black. By visit 4 (1996-98), after an average of 6 years of follow-up, 22% of participants were using lipid-lowering drugs. Compared to never users, current use was associated with 53% lower risk of CRC death (HR 0.47; 95%CI 0.32-0.71). Inverse associations were present in both men (HR 0.59; 95%CI 0.35-0.99) and women (HR 0.37; 95%CI 0.20-0.69) and in Black (HR 0.44; 95%CI 0.19-1.00) and White (HR 0.49; 95%CI 0.31-0.77) participants. Inverse associations were consistent across different patterns of duration of use and was inverse irrespective of age at first use. Current use was also associated with a lower risk of CRC incidence (HR: 0.72; 95%CI 0.57-0.92). Conclusions: Current use of lipid-lowering drugs was associated with a statistically significant lower risk of dying from CRC in participants without cancer at baseline, including men and women and in Black and white participants, irrespective of the duration (15 year intervals) or age at first use. Support: NHLBI contracts, NCI grants, NPCR Citation Format: Michael T. Marrone, John R. Barber, Alison M. Mondul, Anna E. Prizment, David Couper, Corinne E. Joshu, Elizabeth A. Platz. Lipid-lowering drug use, duration of use, and age at first use is associated with a lower risk of colorectal cancer mortality in men and women in the Atherosclerosis Risk in Communities (ARIC) Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2357.

Abstract C106: Multilevel patient navigator-led intervention to optimize colonoscopy completion after an abnormal fecal immunochemical test

Abstract Purpose: Impact of colorectal cancer (CRC) screening with the fecal immunochemical test (FIT) depends on completion of diagnostic colonoscopy after abnormal FIT, as failure to complete diagnostic colonoscopy is associated with 2.4 fold increased risk of CRC death. Colonoscopy completion after abnormal FIT ranges from 18% to 57% among Federally Qualified Health Centers (FQHCs) in San Diego County. Our goal is to report the initial successes and challenges of a multi-level, patient navigator (PN) led intervention to optimize colonoscopy completion after abnormal FIT faced largely by Hispanic/Latino patients in our geographic area. Methods: At a single primary clinic within a large FQHC in San Diego’s predominantly Latino community, we implemented a multi- component intervention to promote colonoscopy completion for patients with abnormal FIT led by a bilingual/bicultural PN. PN responsibilities included monitoring timely review of FIT results by ordering provider, results provision to patients, insurance authorization, facilitating referrals for GI consultation and colonoscopy scheduling. Health system barriers (such as failure to order colonoscopy) were addressed by having the PN prompt the relevant team member to complete required care steps. Patient barriers (such as understanding FIT results, procedure scheduling and fears) were addressed through phone and in-person encounters by the PN. Summary: During the period of March to August 2017, 45 patients had an abnormal FIT. Out of 45 patients, three were not eligible for navigation due to prior colonoscopy completion. Of the remaining 42, 26 did not complete colonoscopy (14 lost to follow-up, 4 pending GI consult, 4 pending colonoscopy, 4 declined). The PN directly interacted with 28 patients of which 16 (57%) successfully completed colonoscopy. These preliminary results show a low overall rate of colonoscopy completion (16/45=36%) with nearly one third of patients (14/45=31%) lost to follow-up. Conclusions: In our initial experience with a PN-led, multi-level intervention for promoting colonoscopy completion after abnormal FIT, 57% of patients who interacted with the PN completed a colonoscopy procedure. Challenges such as loss to follow up remain a barrier to intervention success. Our results suggest that multi-level interventions led by a PN have potential to optimize follow through of colonoscopy completion after abnormal FIT. Citation Format: Monica Hernandez, Jesse Nodora, Balambal Bharti, Jose L Diaz, Jessica Marquez, Felipe Garcia-Bigley, Christian Ramers, Jessica Haughton, Elva Arredondo, Samir Gupta. Multilevel patient navigator-led intervention to optimize colonoscopy completion after an abnormal fecal immunochemical test [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C106.

Epidemiologic Burden of Red and Processed Meat Intake on Colorectal Cancer Mortality

A clear epidemiologic association has been reported between intake of red processed meat and colorectal cancer. Therefore, an electronic search was performed in Global Health Data Exchange (GHDx) registry, using the keywords “diet high in red meat”, “diet high in processed meat”, “colon and rectum cancer” and “death”. According to this search, red and processed meat intake accounts for 1.77% and 1.18% worldwide colorectal cancer mortality, respectively. The death risk attributable to consumption of red meat linearly increased during the past decade (r = 0.99; p < 0.001), whilst that of processed meat exhibited linear decline (r= −0.97; p < 0.001). The risk of colorectal cancer death for both types of meat is higher in men than in women. Colorectal cancer mortality for red meat is mostly clustered in people <75 years, whilst that attributable to processed meat increases with ageing. A positive relationship can be observed between consumption of both meats and socio-demographic index (SDI). The risk of colorectal cancer deaths attributable to red meat is independently associated with male sex, higher SDI and younger age, whilst that of processed meat is independently associated with higher SDI and older age. Reinforced efforts shall be prioritized for broadening recommendations on decreasing red and processed meat consumption.

Colorectal cancer in Crohn's disease: a Scandinavian population-based cohort study

Crohn's disease is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance strategies, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account. Such biases can be accounted for by assessing CRC incidence by tumour stage and CRC mortality by tumour stage. We aimed to assess rates of incident CRC and CRC mortality among patients with Crohn's disease compared with the general population. For this nationwide register-based cohort study, we used International Classification of Disease codes in national patient registers and pathology reports to identify incident cases of Crohn's disease. In Denmark we searched for incident cases between January, 1977, and December, 2011, and in Sweden between January, 1969, and December, 2017. For each patient with Crohn's disease, we identified up to ten reference individuals in national population registers and matched them by sex, age, calendar year, and place of residence. Matched reference individuals had to be alive and free of inflammatory bowel disease at the start of follow-up of index patients with Crohn's disease, and stopped contributing to reference person-years if they were diagnosed with inflammatory bowel disease. Our main outcome was death from CRC (main or contributory cause of death) as captured in the cause-of-death registers. Our secondary outcome was incident CRC, as defined by the cancer registers. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality, taking tumour stage into account. We used a series of Cox models to estimate cause-specific HRs of the different competing outcomes (CRC diagnosis, CRC death, and other causes of death) and adjusted for tumour stage at CRC diagnosis. During the 1969-2017 study period, we identified 47 035 patients with incident Crohn's disease (13 056 in Denmark and 33 979 in Sweden) and 463 187 matched reference individuals. During follow-up, 296 (0·47 per 1000 person-years) CRC deaths occurred among individuals with Crohn's disease compared with 1968 (0·31 per 1000 person-years) in reference individuals, corresponding to an overall adjusted HR of 1·74 (1·54-1·96). 499 (0·82 per 1000 person-years) cases of incident CRC were diagnosed in patients with Crohn's disease compared with 4084 (0·64 per 1000 person-years) cases in reference individuals, corresponding to an overall adjusted HR of 1·40 (95% CI 1·27-1·53). Patients with Crohn's disease who were diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC (HR 1·42 [1·16-1·75] when adjusted for tumour stage), and tumour stage at CRC diagnosis did not differ between groups (p=0·27). Patients with Crohn's disease who had follow-up of 8 years or longer or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death (HR 1·40 [1·16-1·68]) or CRC diagnosis (HR 1·12 [0·98-1·28]). However, in patients potentially eligible for CRC surveillance we only found significantly increased risks in patients diagnosed with Crohn's disease before the age of 40 years, patients with disease activity in the colon only, or patients with PSC. Patients with Crohn's disease are at increased risk of CRC diagnosis and CRC death. Patients with Crohn's disease who have CRC have a higher mortality than patients without Crohn's disease who are also diagnosed with CRC. CRC surveillance should likely be focused on patients diagnosed with Crohn's disease before the age of 40 years, on patients with colon inflammation, and on those who have PSC. Swedish Medical Society, Karolinska Institutet, Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet (ALF), Forte Foundation, Swedish Cancer Foundation, and Independent Research Fund Denmark.

OP14 Risk of colorectal cancer diagnosis and colorectal cancer mortality in Crohn’s disease: A Scandinavian population-based cohort study

Abstract Background Crohn’s disease (CD) is a risk factor for colorectal cancer (CRC). Earlier studies reflect older treatment and surveillance strategies, and most have studied incident CRC without addressing potential lead-time and surveillance biases. Such bias can be reduced by examining tumour stage-adjusted CRC incidence and CRC mortality. We aimed to assess risks of CRC mortality and incident CRC among patients with CD compared with the general population. Methods Nationwide register-based cohort study during 1969–2017 of 47,035 patients with CD in Denmark (n = 13,056) and Sweden (n = 33,979), compared with 463,187 general population reference individuals, matched for sex, age, calendar year, and place of residence. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality. In a multistate model, assessing competing events during follow-up (CRC diagnosis, CRC death, other death), we also took a tumour stage into account. Results During 1969–2017, 499 patients with CD developed CRC, corresponding to an adjusted HR of 1.40 [95% confidence interval (CI) 1.27–1.53]. We observed 296 (0.47/1000 person-years) deaths from CRC in patients with CD compared with 1968 (0.31/1000) in reference individuals [HR 1.74 (95% CI 1.54–1.96)]. CD patients diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC [HR = 1.30 (95% CI 1.06–1.59)] and tumour stage at CRC diagnosis did not differ between groups (p = 0.27). CD patients who had 8 or more years of follow-up or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death [HR 1.41 (95% CI 1.18–1.69)] or CRC diagnosis [HR = 1.12 (95% CI = 0.98–1.28)]. However, in patients potentially eligible for CRC surveillance, we only found significantly increased risks in patients with CD onset &amp;lt;40 years, disease activity in the colon only, or with PSC (Figure 1). Conclusion CD patients are at increased risk of a CRC diagnosis and CRC death. Despite repeated colonoscopies during follow-up, CD patients are not diagnosed earlier (less severe tumour stage) with CRC than reference individuals. Nevertheless, CD patients with CRC have higher mortality than non-CD patients also diagnosed with CRC. CRC surveillance could likely be improved and should be focussed on CD patients &amp;lt;40 years at CD onset, patients with colon inflammation, and patients who have PSC.

1915 Delayed Post-Polypectomy Bleeding Case Report, Using Cold Snare Technique

INTRODUCTION: Most cases of colorectal cancer develop from colorectal polyps, therefore their early detection and removal decreases the risk of colorectal cancer death. Hot snare is the most commonly used endoscopic technique to eradicate colonic polyps with some inevitable post polypectomy bleeding. Cold snare polypectomy has been used recently because of its low risk of immediate and delayed post polypectomy bleeding. CASE DESCRIPTION/METHODS: A 66 y/o female with a history of ascending colon cancer status post right hemicolectomy presented for routine screening colonoscopy. She has a history of coronary artery disease status post stenting, systolic congestive heart failure and mechanical aortic valve for which she is on warfarin for anticoagulation. Warfarin was stopped 7 days before the procedure, without bridging. Colonoscopy showed two small polyps in the descending and sigmoid colon, and these were removed using cold snare. She was stable after colonoscopy and was discharged. Warfarin was restarted on the next day. Five days later she presented to the hospital complaining of bright red bleeding per rectum and bright red blood with stool. Hemoglobin had decreased from 11.4 (gm/dl) on the day of admission to 9.8 (gm/dl) the next day. Repeat colonoscopy was performed and a large clot was seen in the descending colon at one polypectomy site. There was no active bleeding from the clot though there was some minimal oozing with manipulation. The clot was not removed due to concerns of a large defect underneath that might bleed again. The surgery team was consulted during the procedure. Both GI and surgery teams decided not to proceed with any intervention. Another small non-bleeding ulcer in the sigmoid colon measuring 5 mm was seen and likely represent the site of previous polypectomy. She was monitored after the procedure, her symptoms and hemoglobin improved. Warfarin was restarted and discharged in stable condition. DISCUSSION: Cold snare polypectomy is being increasingly used as it is safe and efficient for small polyp removal. Newer polypectomy snares designed for cold snare polypectomy have been developed. This equipment may further decrease complications from smaller polypectomies. We present a case of rare delayed post polypectomy bleeding with the development of a large post polypectomy ulcer, even though anticoagulation was interrupted 7 days before the procedure. We used the traditional polypectomy snare. Results could have been different if the more modern cold snare polypectomy equipment used.

Pre-diagnostic colonoscopies reduce cancer mortality - results from linked population-based data in South Australia

BackgroundTo investigate the association between pre-diagnostic colonoscopy and colorectal cancer mortality in South Australia.MethodsColonoscopy histories were obtained for colorectal cancer patients diagnosed in 2003–2013 using linked Medical Benefits Schedule (MBS) claims, hospital-inpatient and cancer-registry data. Colonoscopy histories included the year of colonoscopy, numbers of examinations, and the time from first colonoscopy to diagnosis. Histories of multiple exposures to colonoscopies, and exposures of greater than a year from initial colonoscopy to diagnosis, were regarded as indicators of screening or surveillance activity. Colonoscopies occurring within one year of diagnosis were regarded as more likely to be a response to cancer symptoms than those occurring > 1 year before diagnosis. Associations between colonoscopy history and post-diagnostic survival were analysed using sub-hazard ratios (SHRs) from competing risk regression adjusted for socio-demographic and cancer characteristics.ResultsHaving pre-diagnostic colonoscopy was associated with an unadjusted reduction in risk of colorectal cancer death of 17% (SHR: 0.83, 95% CI 0.78–0.89). After adjusting for time period and sociodemographic characteristics, the risk of colorectal cancer death reduced by 17% for one pre-diagnostic colonoscopy examination; 27% for two pre-diagnostic colonoscopy examinations; and 45% for three or more pre-diagnostic colonoscopy examinations. Those with a time of over one year from first colonoscopy in the study window to diagnosis, when compared with less than one year, had a 17% lower risk of colorectal cancer death in this adjusted analysis. These reductions were substantially reduced or eliminated when also adjusting for less advanced stage.ConclusionsPre-diagnostic colonoscopy, and more so, multiple colonoscopies and first colonoscopy occurring over one year from initial colonoscopy to diagnosis, were associated with longer survival post diagnosis. This was largely explained by less advanced cancer stage at the time of diagnosis.

MicroRNA-transcription factor interactions and their combined effect on target gene expression in colon cancer cases.

Transcription factors (TFs) and microRNAs (miRNAs) regulate gene expression: TFs by influencing messenger RNA (mRNA) transcription and miRNAs by influencing mRNA translation and transcript degradation. Additionally, miRNAs and TFs alter each other's expression, making it difficult to ascertain the effect either one has on target gene (TG) expression. In this investigation, we use a two‐way interaction model with the TF and miRNA as independent variables to investigate whether miRNAs and TFs work together to influence TG expression levels in colon cancer subjects. We used known TF binding sites and validated miRNA targets to determine potential miRNA‐TF‐TG interactions, restricting interactions to those with a TF previously associated with altered risk of colorectal cancer death. We analyzed interactions using normal colonic mucosa expression as well as differential expression, which is measured as colonic carcinoma expression minus normal colonic mucosa expression. We analyzed 3518 miRNA‐TF‐TG triplets using normal mucosa expression and 617 triplets using differential expression. Normal colonic RNA‐Seq data were available for 168 individuals; of these, 159 also had carcinoma RNA‐Seq data. Thirteen unique miRNA‐TF‐TG interactions, comprising six miRNAs, four TFs, and 11 TGs, were statistically significant after adjustment for multiple comparisons in normal colonic mucosa, and 14 unique miRNA‐TF‐TG interactions, comprising two miRNAs, two TFs, and 13 TGs, were found for carcinoma‐normal differential expression. Our results show that TG expression is influenced by both miRNAs as well as TFs, and the influence of one regulator impacts the effect of the other on the shared TG expression.

Serum inflammatory markers and colorectal cancer risk and survival

Background:Inflammation has been linked with development of some cancers. We investigated systemic inflammation in relation to colorectal cancer incidence and subsequent survival using common serum inflammatory markersDesign:A cohort of men and women aged 20 years and older in greater Stockholm area with serum C-reactive protein (CRP) and albumin measured between 1986 and 1999 were included (n=325 599). A subset of these had baseline measurements of haptoglobin and leukocytes. Multivariable Cox regression was performed to assess risk of colorectal cancer by levels of inflammatory markers, adjusting for potential confounders. Analyses were stratified by circulating glucose, total cholesterol and triglycerides. Overall and CRC-specific death following diagnosis were assessed as secondary outcomes.Results:A total of 4764 individuals were diagnosed with colorectal cancer. A positive association between haptoglobin and colorectal cancer incidence was found (hazard ratio (HR): 1.17; 95% CI: 1.06–1.28). A positive association was also observed with leukocytes (HR: 1.21; 95% CI: 1.03–1.42). No evidence of association was noted between CRP and colorectal cancer risk. Higher risks of all-cause death were seen with haptoglobin and leukocytes levels. Higher haptoglobin levels were linked with an increased risk of colorectal cancer death (HR: 1.19; 95% CI: 1.01–1.41).Conclusions:Prediagnostic systemic inflammation may impact colorectal cancer incidence and survival; therefore, prompting investigations linking inflammatory pathways preceding colorectal cancer with disease severity and progression.

MORTALITY RISK OF COLORECTAL CANCER IN BRAZIL FROM 1980 TO 2013.

Colorectal cancer is one of the most common cancer worldwide, and variation in its mortality rates indicates the importance of environmental factors in its occurrence. While trend studies have indicated a reduction in colorectal cancer mortality rates in most developed countries, the same trends have not been observed in developing countries. Moreover, trends may differ when analyzed by age and sex. - The present study aimed to analyze the trends in risk of colorectal cancer death in Brazil based on sex and age group. Death records were obtained from the Mortality Information System of the Ministry of Health. The risk of death and the average annual percent changes (AAPC) in the mortality rates were estimated using joinpoint analysis of long-term trends from 1980 to 2013. All of the statistical tests were two-sided and had a significance level of 5%. - Colorectal cancer mortality rates were found to have increased in the last 15 years for both sexes and for all age ranges. The rate ratio (RR) was statistically higher at ages 70 to 79 for men (RR: 1.37; 95% CI: 1.26; 1.49) compared to women (RR: 1.14; 95% CI: 1.06; 1.24). Increases in AAPC were observed in both sexes. Although men presented higher percent changes (AAPC: 1.8; 95% CI: 1.1; 2.6) compared to women (AAPC: 1.2; 95% CI: 0.4; 2.0), this difference was not statistically significant. Growth trends in mortality rates occurred in all age groups except for in women over 70. - Unlike Europe and the US, Brazil has shown increases in death rates due to colorectal cancer in the last three decades; however, more favorable trends were observed in women over 70 years old. The promotion of healthier lifestyles in addition to early diagnosis and improved treatment should guide the public health policies targeting reductions in colorectal cancer.

Abstract A89: Estimating potential years of life lost and productivity lost due to avoidable premature colorectal cancer deaths in U.S. counties with lower educational attainment

Abstract Background: Measures of socioeconomic status (SES) are inversely associated with colorectal cancer (CRC) mortality. This study aims to estimate potential years of life lost and productivity lost due to premature cancer deaths among United States residents of lower SES areas, as measured by percentage of high school graduates. Methods: 2008-2012 mortality and population data were used to estimate the number of expected CRC deaths between the ages of 50-74 years by applying the mortality rate from higher SES areas (≥85% high school graduation) to lower SES areas, by race/ethnicity, age, and gender. Excess deaths (observed minus expected deaths) were used to estimate the years of potential life lost (YPLL) and the human capital method was used to estimate productivity lost due to YPLL. Results: Risk of CRC deaths was inversely associated with SES among non-Hispanic whites, non-Hispanic blacks and Hispanics. Of the 85,484 CRC deaths during 2008-2012 in lower SES groups, 16.8% (n=14,398) were potentially preventable if the CRC mortality rates in all areas were the same as higher SES areas. Eliminating avoidable CRC deaths would result in $4.2 billion in productivity gains in men and $2.2 billion in women based on a 3% discount rate. Conclusion: A substantial number of CRC deaths are potentially preventable through routine colorectal screening. SES disparities represent a large number of these deaths and result in a large economic burden in lower SES areas. Eliminating educational disparities could help decrease CRC cancer deaths and associated productivity lost in the US. These estimates do not include the costs to diagnose, treat and care for CRC patients. Citation Format: Hannah K. Weir, Chunyu Li, Jane Henley, Djenaba Joseph. Estimating potential years of life lost and productivity lost due to avoidable premature colorectal cancer deaths in U.S. counties with lower educational attainment. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A89.