Exogenous and Endogenous Risk Factors for Early-onset Colorectal Cancer

An increase in early-onset colorectal cancers (eoCRC), defined as a CRC before 50 years, is confirmed globally. CRC pathogenesis has been associated with several risk factors (family history, germline pathogenic variants, obesity, alcohol, physical activity, red meat, and a Western diet). Design: an international, multicenter, retrospective case-control study of prospectively enrolled patients; low-risk intervention study as it will perform a fecal occult blood test Endpoint: predictive power of a semi-quantitative food frequency questionnaire (SQFFQ) developed for eoCRC. Cases: Patients with a recent diagnosis of eoCRC (within 2 years from enrollment). Controls: matched by age (matching range ± 5 years) and sex. Healthy volunteers will be mainly enrolled among workers within the participating hospital center. The enrolled healthy volunteers will perform a fecal occult blood test. Variables of interest: age, sex, ethnicity, BMI at the time of eoCRC diagnosis and at 18 years old, country, tobacco smoking at the time of eoCRC diagnosis and at 18 years old, sitting time, TV-viewing time, moderate-to-vigorous physical activity (MVPA), waist circumference (cm), home blood pressure levels (mmHg), fasting blood glucose (mg/dl), regular consumption of aspirin/NSAID, calcium and folate supplements, oral contraceptive agents, post-menopausal hormones and years of consumptions, if the filled questionnaire reflects diet for the last 5-10 years before. Cases only: date of eoCRC diagnosis, symptoms at diagnosis, eoCRC localization, eoCRC stage, histological diagnosis, type of surgery, and date (if performed), chemotherapy and radiotherapy (if performed), vital status and duration of follow-up, family history of CRC and other cancers (uterus, ovary, stomach, small intestine, urinary tract/bladder/kidney, bile ducts, brain, pancreas, skin tumors), type of germline pathogenetic variant (if performed). Before the case-control study, three non-consecutive 24-hour Dietary Recalls (24hDRs) will validate the SQFFQ. The SQFFQ will be administered to the validation study group during three non-consecutive calls, including one non-weekday (30-minute 24-h-recall computer-aided personal interview). Primary Objective To measure the relative risk of specific dietary and lifestyle factors (smoking habit, alcohol intake, physical activity) for early-onset colorectal cancer in countries where eoCRC incidence is increasing versus stable/decreasing

Background Firstly described in U.S. series, an increase in early-onset colorectal cancers (eoCRC), defined as CRC before 50 years, is confirmed globally. CRC pathogenesis has been associated with several endogenous and exogenous associated risk factors, including family history of CRC, CRC-related germline pathogenic variants, obesity, alcohol habits, physical activity, red and processed meat and a Western diet. Two dietary patterns appear as exogenous and behavioral factors associated with either CRC prevention or predisposition: the 'healthy' pattern (high in fruits, vegetables, and whole grains or legumes, fish, and low-fat milk or dairy products) and the 'unhealthy' or 'Western dietary' pattern (high in red and processed meat, sugary drinks, refined grains, desserts). Above all, the Western diet is one of the most important CRC risk factors. In the Nurses' Health Study II, Western diet during adolescence was associated with the development of high-risk rectal adenomas later in life. In a meta-analysis of cohort studies, the Western dietary pattern conferred a relative risk (RR) of 1.12 for CRC, compared with a 0.89 RR for the healthy pattern. Conversely, the Mediterranean diet demonstrated a protective role in CRC development, confirmed in the EPIC cohort study. Rationale Dietary, lifestyle, and anthropometric risk factors are still poorly understood in eoCRC patients, despite its established rising incidence. To date, scant studies, mostly case-control and only a few prospective ones, investigated the exogenous risk factors of eoCRCs and eoCRC precursors and identified high intake of alcohol and processed meat, sedentary lifestyle as potential eoCRC risk factors, and obesity as ambiguous one. Primary Objective To compare the associations of specific dietary and lifestyle factors (smoking habit, alcohol intake, physical activity) and anthropometric factors between eoCRC patients and healthy age- and sex-matched controls in countries with increasing versus stable or decreasing early-onset colorectal cancer (eoCRC) incidence. Secondary Objectives 1. To validate the semi-quantitative food frequency questionnaire (SQFFQ); 2. To evaluate the consistency of associations across cohorts in pairwise comparisons; 3. To assess whether associations differ among specific population subgroups (e.g., sex, ethnicity, smoking habits, BMI, physical activity, family history of CRC). Type of study SQFFQ validation study: three non-consecutive 24-hour Dietary Recalls (24hDRs) will validate the ad hoc designed and shared SQFFQ, as previously performed \[28-29\]. The SQFFQ will be administered to the validation study group during three non-consecutive calls, including one non-weekday (30 minutes 24-h-recall computer-aided personal interview). Case-control study: an international, multicentre, retrospective case-control study of prospectively enrolled patients will be performed to evaluate the associations of dietary, anthropometric, lifestyle factors in eoC Покажи пълното описание...

Inclusion Criteria: * All sexes eligible * (for Cases) eoCRC diagnosed between 18 and 49 years and confirmed by histology (biopsy or surgical specimen in case of surgery) * (for Controls) negative past and present history of cancer; negative fecal occult blood test (FOBT), or negative colonoscopy. Exclusion Criteria: * CRC diagnosed at ≥ 50 years * Diseases that can modify the dietary regimen (celiac disease, diabetes) * Diseases that are known to predispose to eoCRC (personal past or recent history of inflammatory bowel disease, past history of pelvic irradiation) * Unable to give written consents and to fill in the electronic questionnaire