Risk Of Early-onset Colorectal Cancer Research Articles

Colon Age: A Metric for Whether and How to Screen Male Veterans for Early-Onset Colorectal Cancer.

We aimed to develop a metric for estimating risk for early-onset colorectal cancer (EOCRC) to help decide whether and how to screen persons < age 50. We used risk prediction models derived and validated on male Veterans to calculate the relative risks (RRs) for 6 scenarios: one low-risk scenario (no risk factors present), four intermediate risk scenarios (some factors present), and one high-risk scenario (all factors present) for three age groups (35-39, 40-44, and 45-49 years). For each scenario, we estimated absolute CRC risk using SEER CRC incidence rates and each scenario's RR. We identified the current SEER 5-year age group to which the revised estimate was closest and refer to the midpoint of this group as the "colon age". When the revised estimate was ≥ that for 50-54-year-olds and for 70-74-year-olds, respective recommendations were made for (any) CRC screening and screening with colonoscopy. Among the scenarios, there was inconsistency between the two models for the 35-39 and 40-44 age groups, with only the 15-variable model recommending screening for the higher-risk 35-to-39-year-olds. Both models recommended screening for some intermediate risk and high-risk 40-44-year-olds. The models were well-aligned on whether and how to screen most 45-49-year-olds. Using risk factors for EOCRC with CRC incidence rates, "colon age" may be useful for shared decision making about whether and how to screen male Veterans < 50 years. For 45-49-year-olds, the 7-variable model may be preferred by patients, providers, and health systems.

Obesity and early-onset colorectal cancer risk: emerging clinical evidence and biological mechanisms.

Early-onset colorectal cancer (EOCRC) is defined as diagnosed at younger than 50 years of age and indicates a health burden globally. Patients with EOCRC have distinct risk factors, clinical characteristics, and molecular pathogenesis compared with older patients with CRC. Further investigations have identified different roles of obesity between EOCRC and late-onset colorectal cancer (LOCRC). Most studies have focused on the clinical characteristics of obesity in EOCRC, therefore, the mechanism involved in the association between obesity and EOCRC remains inconclusive. This review further states that obesity affects the carcinogenesis of EOCRC as well as its development and progression, which may lead to obesity-related metabolic syndrome, intestinal dysbacteriosis, and intestinal inflammation.

Number of Older Biologic Siblings and Early-Onset Colorectal Cancer Risk

Colorectal cancer (CRC) is the third most common cancer in the United States.1 Although CRC incidence has declined in individuals >50 years, incidence is rising in adults <50 years (early onset).1 By 2027, CRC is projected to become the leading cause of cancer mortality in US adults <50 years.2 To combat the rising incidence of early onset CRC (EOCRC), national guidelines recently lowered the screening age from 50 to 45 years for average-risk individuals.3 Understanding the risk profile of EOCRC can help combat the rising burden in young adults, especially in those ineligible for screening.

A Perspective Review on Diet Quality, Excess Adiposity, and Chronic Psychosocial Stress and Implications for Early-Onset Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer worldwide. Although the overall incidence of CRC has been decreasing over the past 40 y, early-onset colorectal cancer (EOCRC), which is defined as a CRC diagnosis in patients aged >50 y has increased. In this Perspective, we highlight and summarize the association between diet quality and excess adiposity, and EOCRC. We also explore chronic psychosocial stress (CPS), a less investigated modifiable risk factor, and EOCRC. We were able to show that a poor-quality diet, characterized by a high intake of sugary beverages and a Western diet pattern (high intake of red and processed meats, refined grains, and foods with added sugars) can promote risk factors associated with EOCRC development, such as an imbalance in the composition and function of the gut microbiome, presence of chronic inflammation, and insulin resistance. Excess adiposity, particularly obesity onset in early adulthood, is a likely contributor of EOCRC. Although the research is sparse examining CPS and CRC/EOCRC, we describe likely pathways linking CPS to tumorigenesis. Although additional research is needed to understand what factors are driving the uptick in EOCRC, managing body weight, improving diet quality, and mitigating psychosocial stress, may play an important role in reducing an individual’s risk of EOCRC.

Pharmaceutical Agents as Potential Drivers in the Development of Early-Onset Colorectal Cancer: Case-Control Study.

The incidence of early-onset colorectal cancer (EOCRC) rose abruptly in the mid 1990s, is continuing to increase, and has now been noted in many countries. By 2030, 25% of American patients diagnosed with rectal cancer will be 49 years or younger. The large majority of EOCRC cases are not found in patients with germline cancer susceptibility mutations (eg, Lynch syndrome) or inflammatory bowel disease. Thus, environmental or lifestyle factors are suspected drivers. Obesity, sedentary lifestyle, diabetes mellitus, smoking, alcohol, or antibiotics affecting the gut microbiome have been proposed. However, these factors, which have been present since the 1950s, have not yet been conclusively linked to the abrupt increase in EOCRC. The sharp increase suggests the introduction of a new risk factor for young people. We hypothesized that the driver may be an off-target effect of a pharmaceutical agent (ie, one requiring regulatory approval before its use in the general population or an off-label use of a previously approved agent) in a genetically susceptible subgroup of young adults. If a pharmaceutical agent is an EOCRC driving factor, regulatory risk mitigation strategies could be used. We aimed to evaluate the possibility that pharmaceutical agents serve as risk factors for EOCRC. We conducted a case-control study. Data including demographics, comorbidities, and complete medication dispensing history were obtained from the electronic medical records database of Maccabi Healthcare Services, a state-mandated health provider covering 26% of the Israeli population. The participants included 941 patients with EOCRC (≤50 years of age) diagnosed during 2001-2019 who were density matched at a ratio of 1:10 with 9410 control patients. Patients with inflammatory bowel disease and those with a known inherited cancer susceptibility syndrome were excluded. An advanced machine learning algorithm based on gradient boosted decision trees coupled with Bayesian model optimization and repeated data sampling was used to sort through the very high-dimensional drug dispensing data to identify specific medication groups that were consistently linked with EOCRC while allowing for synergistic or antagonistic interactions between medications. Odds ratios for the identified medication classes were obtained from a conditional logistic regression model. Out of more than 800 medication classes, we identified several classes that were consistently associated with EOCRC risk across independently trained models. Interactions between medication groups did not seem to substantially affect the risk. In our analysis, drug groups that were consistently positively associated with EOCRC included beta blockers and valerian (Valeriana officinalis). Antibiotics were not consistently associated with EOCRC risk. Our analysis suggests that the development of EOCRC may be correlated with prior use of specific medications. Additional analyses should be used to validate the results. The mechanism of action inducing EOCRC by candidate pharmaceutical agents will then need to be determined.

Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes.

Early-onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early-life factors and EOCRC risk, with a particular focus on long-term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC-related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early-onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early-life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early-onset CRC (OR = 1.48, 95% CI = 1.01-2.17, P = .046) and adenomas (OR = 1.40, 95% CI = 1.17-1.68, P < .001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early-onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79-1.52, P = .587, for CC genotype; OR = 1.75, 95% CI = 1.16-2.64, P = .008, for TT genotype; Pinteraction = .089). Our study suggested that LRAU during early life is associated with increased risk of early-onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome-related pathway underlying colorectal carcinogenesis, are warranted.

Association of changes in obesity and abdominal obesity status with early-onset colorectal cancer risk: a nationwide population-based cohort study.

The incidence of early-onset colorectal cancer (EO-CRC, diagnosed before 50 years of age) has increased in recent decades. The aim of this study was to investigate the association between changes in obesity status and EO-CRC risk. From a nationwide population-based cohort, individuals <50 years old who participated in the national health checkup program in both 2009 and 2011 were included. Obesity was defined as a body mass index ≥25 kg/m2. Abdominal obesity was defined as a waist circumference ≥ 90 cm in men and ≥ 85 cm in women. Participants were classified into 4 groups according to the change in obesity (normal/normal, normal/obese, obese/normal, persistent obese) and abdominal obesity (normal/normal, normal/abdominal obesity, abdominal obesity/normal, persistent abdominal obesity) status. Participants were followed up until 2019 and censored when they became 50 years old. Among 3,340,635 participants, 7,492 patients were diagnosed with EO-CRC during 7.1 years of follow-up. The risk of EO-CRC was higher in the persistent obesity and persistent abdominal obesity groups than in the normal/normal groups (hazard ratio (HR) [95% confidence interval (CI)] = 1.09 [1.03-1.16] and 1.18 [1.09-1.29], respectively). Participants with both persistent obesity and abdominal obesity had a higher EO-CRC risk than those in the normal/normal groups for both [HR (95% CI) = 1.19 (1.09-1.30)]. Persistent obesity and persistent abdominal obesity before the age of 50 are associated with a slightly increased risk of EO-CRC. Addressing obesity and abdominal obesity in young individuals might be beneficial in reducing the risk of EO-CRC.

Sex and Tumor-Site Differences in the Association of Alcohol Intake With the Risk of Early-Onset Colorectal Cancer.

Given the increasing incidence of early-onset colorectal cancer (CRC; diagnosed before age 50 years) worldwide, it is important to identify modifiable risk factors. We investigated whether alcohol consumption in the young population correlated with an increased early-onset CRC risk that differed by tumor location and sex. We investigated the association between average daily alcohol consumption and the risk of early-onset CRC among 5,666,576 individuals age 20-49 years using data from the Korean National Health Insurance Service (2009-2019). Alcohol consumption levels of nondrinker, light (reference), moderate, and heavy drinker were defined as 0, <10, 10 to <30, and ≥30 g/d for men and 0, <10, 10 to <20, and ≥20 g/d for women, respectively. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% CIs. We identified 8,314 incident early-onset CRC cases during the follow-up period. Moderate and heavy drinkers showed an increased risk of early-onset CRC compared with light drinkers (aHR, 1.09 [95% CI, 1.02 to 1.16] and aHR, 1.20 [95% CI, 1.11 to 1.29], respectively). Subgroup analysis by tumor location showed positive dose-response significance for early-onset distal colon and rectal cancers, but not for proximal colon cancer. The dose-response association between drinking frequency and risk of early-onset CRC was significant, with a 7%, 14%, and 27% increased risk for 1-2, 3-4, and ≥5 d/wk compared with nondrinkers, respectively. Excessive alcohol consumption increases the risk of CRC onset before age 50 years. Thus, effective interventions are required to discourage alcohol consumption among young people and to tailor CRC screening approaches for high-risk individuals.

Impact of bariatric surgery on early-onset colorectal cancer risk: a systematic review and meta-analysis.

The aim of this meta-analysis is to determine the impact of bariatric surgery on the risk of early-onset colorectal neoplasia. This systematic review was conducted according to PRISMA recommendations. It was registered in the PROSPERO international database. A comprehensive search was conducted in electronic databases (MEDLINE, EMBASE, and Web of Science) for completed studies until May 2022. The Search was made using a mixture of indexed terms and title, abstract and keywords. The search included terms: obese, surgical weight loss intervention, colorectal cancer, and colorectal adenomas. Studies that included bariatric intervention patient's vs non-surgical obese patients younger than 50years were considered. Inclusion criteria were patients with BMI more than 35kg/m2 who underwent a colonoscopy. Studies with follow-up colonoscopy performed in less than 4years after bariatric surgery and those that evaluated patients with a mean age difference of 5 or more years between groups were excluded. Outcomes analyzed in obese patients with surgical treatment vs control patients included colorectal cancer incidence. From 2008 to 2021, a total of 1536 records were identified. Five retrospective studies that included 48,916 patients were analyzed. Follow-up period ranged from 5 to 22.2years. 20,663 (42.24%) patients underwent bariatric surgery and 28,253 (57.76%) were part of the control patients. Roux-en-Y gastric bypass was performed in 14,400 (69.7%) individuals. The intervention and control group were similar in age range, proportion of female participants and initial body mass index (35-48.3 vs 35-49.3, respectively). 126/20663 (0.61%) patients in the bariatric surgery group and 175/28253 (0.62%) individuals in the control group presented CRC. In this meta-analysis, we were unable to demonstrate a significant impact of the Bariatric Surgery on EOCRC risk. Prospective trials with longer follow-up periods should be done to prove the colorectal cancer risk reduction.

A Qualitative Study of a New Metric for Estimating the Risk of Early-onset Colorectal Cancer in Male Veterans

Background: Identifying patients who benefit from screening prior to ages 45 or 50 through risk-prediction models may improve the uptake and effectiveness of colon cancer (CRC) screening. “Colon Age” is a way to estimate a person’s risk for CRC in Veterans younger than age 50. The purpose of this study is to determine what patients and primary care providers think about the “Colon Age” concept in terms of its comprehensibility, acceptability, and utility for decision-making about CRC screening.&#x0D; Methods: Veteran patients &lt; 50 years old and primary care providers (PCPs) were recruited from the Roudebush VAMC’s outpatient clinics. Semi-structured, qualitative interviews were conducted one-on-one and included Likert-scale and open-ended questions. The estimate of colon age is based on relating a person’s individual features to the 5-year age group in the U.S. population of men with the closest risk of CRC based on Surveillance, Epidemiology, and End Result cancer incidence data.&#x0D; Results: 19 patients and 8 PCPs were recruited. The majority of patients (68%) had a colon age below that of their biological age, while 2 of 19 (11%) had a higher colon age. PCPs identified the tool’s potential to promote screening uptake, facilitate discussion between patients and PCPs, and adhere to current practices as facilitators. Identified barriers among PCPs and patients included questions about tool accuracy and validation, patient reluctance to receive any form of screening, and limited perceived utility for patients between the ages 45-49.&#x0D; Conclusions and Potential Impact: Using the concept of colon age to express individual patient risk for early-onset CRC was well-received among almost all veteran patients and physicians interviewed.Colon-age adapted screening tools should be incorporated into theelectronic health record reminders to facilitate decision-making and screening uptake.Colon-age based personalized screening has the potential to improve cancer detection by providing individualized recommendations.

Autoimmune and Metabolic Diseases and the Risk of Early-Onset Colorectal Cancer, a Nationwide Nested Case-Control Study.

Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case-control study, we included all EOCRC cases in Sweden diagnosed during 2007-2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66-1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78-7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57-5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.

Abstract IA017: Microbiota drivers of colorectal cancer and their translation to prevention

Abstract Abundant data support that the microbiota, both communities and individual pathogenic bacteria, promote the development of colorectal cancer (CRC). More limited data support that CRC is initiated by specific bacteria or communities. This talk will focus on bacterial contributors to CRC pathogenesis, potential mechanisms, gaps in knowledge and potential approaches to enabling use of the colon microbiota and its members to advance CRC prevention. Improved approaches to prevention are particularly key to identify those at risk for early onset CRC that represents a global change in CRC epidemiology. Citation Format: Cynthia L. Sears. Microbiota drivers of colorectal cancer and their translation to prevention [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA017.

Risk of Metachronous Colorectal Cancer in Lynch Syndrome: Who Needs an Extended Resection?

Lynch syndrome (LS) is the most common genetic condition associated with early-onset colorectal cancer. It is inherited in an autosomal dominant fashion. The increased cancer risk is due to a germline mutation in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) or the EPCAM gene. This leads to a deficient DNA mismatch repair mechanism, resulting in the accumulation of nucleotide changes and microsatellite instability, providing phenotypical evidence that MMR is not functioning normally. LS is associated with a high risk of early-onset colorectal cancer and recurrence. Thus, when undergoing surgery for primary colorectal cancer, extended resection should be discussed with the patient. This review provides an overview of current surgical risk-reducing strategies in LS-associated colorectal cancer. Surgical treatment for LS carriers with colorectal cancer needs to be highly individualized, based on patient and disease characteristics. Strategies are presented to guide decision making in pathologic MMR gene mutation carriers undergoing surgery for colorectal cancer.

Early-Onset Colorectal Cancer Survival Differences and Potential Geographic Determinants Among Men and Women in Utah.

By 2030, early-onset colorectal cancer (EOCRC) is expected to become the leading cancer-related cause of death for people age 20 to 49. To improve understanding of this phenomenon, we analyzed the geographic determinants of EOCRC in Utah by examining county-level incidence and mortality. We linked data from the Utah Population Database to the Utah Cancer Registry to identify residents (age 18-49) diagnosed with EOCRC between 2000 and 2020, and we used spatial empirical Bayes smoothing to determine county-level hotspots. We identified 1,867 EOCRC diagnoses (52.7% in male patients, 69.2% in non-Hispanic White patients). Ten counties (34%) were classified as hotspots, with high EOCRC incidence or mortality. Hotspot status was unrelated to incidence rates, but non-Hispanic ethnic-minority men (incidence rate ratio, 1.49; 95% CI, 1.15-1.91), Hispanic White men and women (incidence rate ratio, 2.24; 95% CI, 2.00-2.51), and Hispanic ethnic-minority men and women (incidence rate ratio, 4.59; 95% CI, 3.50-5.91) were more likely to be diagnosed with EOCRC. After adjustment for income and obesity, adults living in hotspots had a 31% higher hazard for death (HR, 1.31; 95% CI, 1.02-1.69). Survival was poorest for adults with a late-stage diagnosis living in hotspots (chi square (1) = 4.0; p = .045). Adults who were married or who had a life partner had a lower hazard for death than single adults (HR, 0.73; 95% CI, 0.58-0.92). The risk for EOCRC is elevated in 34% of Utah counties, warranting future research and interventions aimed at increasing screening and survival in the population age 18 to 49.

Editors' Selections from Relevant Scientific Publications

Transient bacterial infection leads to colon tumorigenesis (art work from Cancer Discovery)New research links the enteropathogenic and enterohemorrhagic strains of Escherichia coli bacteria responsible for hundreds of millions of cases of diarrheal disease annually to heightened cancer risk. Liu et al. have identified a genotoxin produced by the murine counterpart of these pathogens, Citrobacter rodentium, that can fuel onset of colon cancer. This protein, UshA, inflicted considerable genomic damage on murine colon epithelial cells even after transient exposure, and C. rodentium infection led to accelerated tumorigenesis in a cancer-prone mouse model. UshA is also produced by human-infecting E. coli, and this mechanism could pose a critical link between high prevalence of diarrheal disease and climbing colon cancer rates in sub-Saharan Africa.Liu Y, … Wan F. Cancer Discov. 2022 Jan;12(1):236-249.Illustration of breast tumor and tumor microenvironment (adapted from an image by Adrián Blanco-Gómez for Cancer Research)This HTAN Breast PreCancer Atlas study of ductal carcinoma in situ (DCIS) used a multiplex ion beam imaging by time of flight and a 37-plex antibody staining panel to analyze tumor microenvironment (TME) in 79 patient-matched surgical samples. Risom et al. found four TME states that were defined based on the location and function of myoepithelium, fibroblasts, and immune cells. Critically, disruption of the myoepithelial was more advanced in DCIS patients that did not develop invasive breast cancer, suggesting this process could be protective against disease recurrence. This study improves understanding of the drivers of breast cancer relapse and emphasizes the crucial role of TME in disease progression.Risom T, … Angelo M. Cell. 2022 Jan 20;185(2):299-310.e18.Ductal carcinoma in situ (by Kauczuk via Wikimedia Commons)This histological, molecular, and immunological profiling study explored the diverse, interconnected immune landscapes in 39 premalignant lesions from patients with ductal carcinoma in situ. Nachmanson et al. used multiple microdissected regions to analyze phenotype and subtype heterogeneity, B- and T-lymphocyte spatial analysis, mutational profiling, driver mutations, and immunological status. The authors successfully isolated regions within the same sample to characterize different histological features and infer phylogenetic relationships. This study provided richness to the breast pre-cancer atlas and contributed to better models for outcomes and progress risk.Nachmanson D, …Harismendy O. NPJ Breast Cancer. 2022 Jan 13;8(1):6.Illustration of gene variants and cancer cumulative risk (adapted from figures by Michael J. Hall for Cancer Prevention Research)A pair of recent clinical studies identified nine genes that, when disrupted by truncating or missense mutations, can meaningfully increase breast cancer risk. The researchers of the Breast Cancer Association Consortium have now conducted a follow-up investigation of nearly 90,000 participants from one of these trials, BRIDGES, to determine which tumor types are associated with these mutations. This analysis revealed distinctive patterns in terms of age of onset and histological type—for example, triple-negative tumors were notably overrepresented in women with BRCA1 or BARD1 mutations. These results could thus enable more accurate risk prediction based on genetic test results and inform the development of improved screening guidelines.Breast Cancer Association Consortium, … Easton DF. JAMA Oncol. 2022 Jan 27:e216744.44.Colorectal cancer (by Dcoetzee via Wikimedia Commons)People who were obese in early adulthood have an increased risk of early-onset colorectal cancer later in life. Obesity has long been known as a risk factor for many cancers, but weight loss prior to diagnosis can confound the association. Li et al. analyzed the medical records of 6602 colorectal cancer patients enrolled in a German screening study and compared them to 7950 matched controls. They found that people who had been obese at age 20 or 30 were 2.6 times and 2 times, respectively, more likely to develop colorectal cancer before age 55 as those of normal weight at those ages. The authors say that body mass history, not just current weight, should be considered when assessing a person's risk of colorectal cancer.Li H, … Brenner H. Gastroenterology. 2021 Dec 13:S0016-5085(21)04074-9.Illustration of declines in cancer screening and diagnosis due to the Covid-19 pandemic (SARS-Cov-2 image is by Iketsi via Wikimedia Commons)Cancer screenings and diagnosis procedures – and the number of new cancers diagnosed – declined significantly due to the Covid-19 pandemic. Restrictions on elective medical procedures resulted in the widespread cancellation of appointments and decreased many people's access to care. Englum et al. reviewed the medical records of more than 9 million veterans who visited 1244 Veterans’ Affairs facilities across the United States between 2016 and 2020. They found that these facilities performed 45% fewer colonoscopies in 2020 than the average from previous years, as well as fewer CT scans, biopsies, and cystoscopies. The number of new cancer diagnoses dropped by 13% to 23%, which the authors say necessitates a recovery plan to ensure that health centers can catch up with the backlog and meet the needs of patients whose healthcare access was disrupted.Englum BR… Lal BK. Cancer. 2022 Mar 1;128(5):1048-1056.

A risk scoring system to predict the individual incidence of early-onset colorectal cancer

BackgroundThe incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate and further studies are needed to identify risk factors and to develop prevention strategies.MethodsRisk factors significantly associated with EOCRC were identified using meta-analysis. An individual risk appraisal model was constructed using the Rothman–Keller model. Next, a group of random data sets was generated using the binomial distribution function method, to determine nodes of risk assessment levels and to identify low, medium, and high risk populations.ResultsA total of 32,843 EOCRC patients were identified in this study, and nine significant risk factors were identified using meta-analysis, including male sex, Caucasian ethnicity, sedentary lifestyle, inflammatory bowel disease, and high intake of red meat and processed meat. After simulating the risk assessment data of 10,000 subjects, scores of 0 to 0.0018, 0.0018 to 0.0036, and 0.0036 or more were respectively considered as low-, moderate-, and high-risk populations for the EOCRC population based on risk trends from the Rothman–Keller model.ConclusionThis model can be used for screening of young adults to predict high risk of EOCRC and will contribute to the primary prevention strategies and the reduction of risk of developing EOCRC.

P119 Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases: an ECCO CONFER Multicenter Case Series

Abstract Background Hereditary colorectal cancer syndromes (HCCS) are rare polyposis or nonpolyposis syndromes with a higher risk of developing colorectal cancer (CRC). Coexisting inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), with HCCS is exceedingly rare and presumably increases the risk of early-onset colorectal cancer. Methods This was a multicenter case series performed as a part of the European Crohn’s and Colitis Organisation (ECCO) Collaborative Network of Exceptionally Rare case reports (CONFER) project. Results This report includes 26 patients with IBD (10 UC, 15 CD, and one with IBD unclassified (IBD-U)) and concomitant HCCS. Among these 26 patients (median age 33 years, IQR 20–44), 15 (57.7%) were males, 24 (92.3%) Caucasians and 2 (7.7%) of Arab origin. Among patients with UC, 4 (40%) had proctitis, 3 (30%) left-sided colitis and 3 (30%) an extensive disease; while, among patients with CD, 8 (53.3%) had ileal, 5 (33.3%) ileocolonic, 2 (13.3%) colonic disease. One of these patients had ileocolonic disease associated with upper disease location and six (40%) had an associated perianal disease. Many of patients with CD had a non-stricturing non-penetrating phenotype (53.3%, n=8), while 20.0% (n=3) and 26.7% (n=4) had a stricturing or penetrating phenotype, respectively. HCCS was diagnosed before the IBD diagnosis in 11 patients (42.3%), after diagnosis of IBD in 11 patients (42.3%) and concurrently in 4 patients (15.4%). Sixteen patients had Lynch syndrome, 7 had FAP, 2 had AFAP and one had MAP. The most frequent genetic mutations were those of APC (n=7) and MLH1 (n= 7). Thirteen patients were treated with immunomodulatory (IMM) therapy. During IMM therapy, only 5 patients developed drug-induced side-effects which did not require drug interruption. One patient treated with vedolizumab developed CRC, despite yearly colonoscopy surveillance, after 4 years of treatment. Overall, CRC developed in 38.5% of patients (n=10): in 5 patients (50%) after IBD diagnosis, in 4 (40%) patients before IBD diagnosis, and in 1 patient the 2 conditions were diagnosed simultaneously. Eighteen (69.2%) patients underwent colectomy or abdominal surgery: 9 patients due to CRC diagnosis, 7 patients preventively due to the underlying HCCS and 2 patients because of active IBD disease. On follow-up, one patient died due to CRC. Conclusion This case series describes the largest series to date of patients with IBD patients and HCCS, with special emphasis on the use of IMM in this population. The most frequent diagnosis of HCCS associated with IBD was Lynch syndrome. These data demonstrate the high malignancy rate and surgical intervention rate in this IBD cohort. The optimal medical approach still needs to be addressed.

Antibiotic Therapy and Risk of Early-Onset Colorectal Cancer: A National Case-Control Study.

INTRODUCTION:Antibiotic use has emerged as a risk factor for colorectal neoplasia and is hypothesized as a contributor to the rising incidence of colorectal cancer under age 50 years or early-onset colorectal cancer (EOCRC). However, the impact of antibiotic use and risk of EOCRC is unknown.METHODS:We conducted a population-based case-control study of CRC among individuals aged ≥18 years in the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort (2006–2016). The primary outcome was EOCRC. A secondary outcome was CRC at any age. Incident CRC was pathologically confirmed, and for each, up to 5 population-based controls were matched on age, sex, county of residence, and calendar year. We assessed prescriptions until 6 months before CRC diagnosis. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).RESULTS:We identified 54,804 cases of CRC (2,557 EOCRCs) and 261,089 controls. Compared with none, previous antibiotic use was not associated with EOCRC risk after adjustment for potential confounders (aOR 1.06, 95% CI: 0.96, 1.17) with similarly null findings when stratified by anatomic tumor site. In contrast, previous antibiotic use was weakly associated with elevated risk for CRC at any age (aOR 1.05, 95% CI: 1.02, 1.07). A potential but modest link between broad-spectrum antibiotic use and EOCRC was observed (aOR 1.13, 95% CI: 1.02, 1.26).DISCUSSION:We found no conclusive evidence that antibiotics are associated with EOCRC risk. Although antibiotic use was weakly associated with risk of CRC at any age, the magnitude of association was modest, and the study period was relatively short.

Type 2 Diabetes and Risk of Early-Onset Colorectal Cancer

Background and AimsEarly-onset colorectal cancer (CRC) is increasing in many developed countries. Type 2 diabetes mellitus has increased substantially in younger adults; however, its role in early-onset CRC remains unidentified.MethodsWe conducted a claims-based nested case-control study using IBM MarketScan Commercial Database (2006–2015). Incident early-onset CRC diagnosed at ages 18–49 was identified by the International Classification of Diseases, ninth Revision, Clinical Modification diagnosis code, and the first coded diagnostic pathology date was assigned as the index date. Controls were frequency matched with cases. Type 2 diabetes, stratified by severity, was identified through International Classification of Diseases, ninth Revision, Clinical Modification using the Klabunde algorithm. Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsA total of 6001 early-onset CRC and 52,104 controls were included. Type 2 diabetes was associated with an increased risk of early-onset CRC (5.0% in cases vs 3.7% in controls; OR = 1.24, 95% CI: 1.09–1.41). The positive association was more pronounced for uncontrolled (OR = 1.37; 95% CI: 1.12–1.67) or complicated (OR = 1.59, 95% CI: 1.08–2.35) type 2 diabetes compared with controlled diabetes (OR = 1.13, 95% CI: 0.94–1.36).ConclusionIndividuals with type 2 diabetes have a higher risk of early-onset CRC, with stronger associations for uncontrolled diabetes and complicated diabetes. The rising prevalence of type 2 diabetes among younger adults may partially contribute to the increasing incidence of early-onset CRC. Early-onset colorectal cancer (CRC) is increasing in many developed countries. Type 2 diabetes mellitus has increased substantially in younger adults; however, its role in early-onset CRC remains unidentified. We conducted a claims-based nested case-control study using IBM MarketScan Commercial Database (2006–2015). Incident early-onset CRC diagnosed at ages 18–49 was identified by the International Classification of Diseases, ninth Revision, Clinical Modification diagnosis code, and the first coded diagnostic pathology date was assigned as the index date. Controls were frequency matched with cases. Type 2 diabetes, stratified by severity, was identified through International Classification of Diseases, ninth Revision, Clinical Modification using the Klabunde algorithm. Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A total of 6001 early-onset CRC and 52,104 controls were included. Type 2 diabetes was associated with an increased risk of early-onset CRC (5.0% in cases vs 3.7% in controls; OR = 1.24, 95% CI: 1.09–1.41). The positive association was more pronounced for uncontrolled (OR = 1.37; 95% CI: 1.12–1.67) or complicated (OR = 1.59, 95% CI: 1.08–2.35) type 2 diabetes compared with controlled diabetes (OR = 1.13, 95% CI: 0.94–1.36). Individuals with type 2 diabetes have a higher risk of early-onset CRC, with stronger associations for uncontrolled diabetes and complicated diabetes. The rising prevalence of type 2 diabetes among younger adults may partially contribute to the increasing incidence of early-onset CRC.

Associations of Body Mass Index at Different Ages With Early-Onset Colorectal Cancer

Incidence of colorectal cancer (CRC) in younger adults is increasing in many countries. Given the established association of body mass index (BMI) with CRC risk and the increasing obesity prevalence among younger generations, we aimed to evaluate the association of BMI at different ages during early adulthood with early-onset CRC. Among 6602 patients with CRC and 7950 matched controls who were recruited in 2003-2020 in the Darmkrebs: Chancen der Verhütung durch Screening study, a population-based case-control study from Germany, 747 patients and 621 controls were younger than 55 years and included in this analysis. Self-reported height and weight at ages 20 years and 30 years and at approximately 10 years before diagnosis or interview were recorded in personal interviews. Associations of BMI with early-onset CRC were estimated using multiple logistic regression. Compared with participants with BMI <25 kg/m2, those with BMI ≥30 kg/m2 (obesity) at ages 20 years and 30 years and approximately 10 years before diagnosis or interview had 2.56- (95% confidence interval, 1.20-5.44), 2.06- (confidence interval, 1.25-3.40), and 1.88- (95% confidence interval, 1.30-2.73) fold risk of early-onset CRC. The association of BMI with early-onset CRC risk was particularly pronounced among, and essentially restricted to, the majority of participants with no previous colonoscopy. Obesity at early adulthood is strongly associated with increased risk of early-onset CRC. German Clinical Trials Register ID: DRKS00011793.