Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis

O’Sullivan, Dylan E.; Sutherland, Robert L.; Town, Susanna; Chow, Kristian; Fan, Jeremy; Forbes, Nauzer; Heitman, Steven J.; Hilsden, Robert J.; Brenner, Darren R.

doi:10.1016/j.cgh.2021.01.037

Cited by 191 publications

(147 citation statements)

References 46 publications

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“…While our study confirmed previous findings that family history of CRC is a strong risk factor for EO-CRC [ 15 , 16 , 19 – 23 ], we did not observe an association for several factors known to affect overall CRC risk, including smoking, alcohol, and aspirin/NSAID. Findings from previous EO-CRC studies regarding these factors have also been inconsistent and inconclusive [ 15 , 16 , 19 – 21 , 23 , 24 , 31 ], although a recent meta-analysis of EO-CRC risk factors reported a significant association for alcohol consumption (heavy vs. non-drinkers) based on only three studies (pooled relative risk [RR] 1.71; 95% CI 1.62–1.80) [ 15 ]. A possible explanation for the general lack of associations may be the long latency required [ 32 , 33 ] such that established associations with overall (primarily older-onset) CRC may not hold up for EO-CRC.…”

Section: Discussionsupporting

confidence: 86%

“…This hypothesis is supported by the relatively consistent association observed between smoking (as well as alcohol intake) and early-onset colorectal adenoma [ 34 – 39 ]. Meanwhile, an association between smoking (or tobacco use) and EO-CRC risk was only seen in three cohort studies relying on EHR data [ 19 – 21 ], but not in three other case–control studies [ 23 , 24 , 31 ] or the meta-analysis (pooled RR 1.35; 95% CI 0.81–2.25) [ 15 ]. Reasons for the increased risk we observed for tertile 1 (vs. never) of smoking pack-years, but not higher tertiles, are unclear and may be a spurious finding.…”

Section: Discussionmentioning

confidence: 99%

“…The rising incidence of EO-CRC has sometimes been attributed to the obesity epidemic [ 51 ]. A recent meta-analysis of 7 studies identified obesity as a significant risk factor for EO-CRC (pooled RR 1.54; 95% CI 1.01–2.35); however, cross-sectional studies were included in the analysis and considerable heterogeneity was detected across studies [ 15 ]. The suggestive inverse association between BMI and EO-CRC risk in our study contradicts results from the meta-analysis [ 15 ], as well as those from the Nurses’ Health Study [ 17 ] and analyses of a large EHR database in the US [ 20 , 21 ], which reported increased risks associated with obesity.…”

Section: Discussionmentioning

confidence: 99%

“…A recent meta-analysis of 7 studies identified obesity as a significant risk factor for EO-CRC (pooled RR 1.54; 95% CI 1.01–2.35); however, cross-sectional studies were included in the analysis and considerable heterogeneity was detected across studies [ 15 ]. The suggestive inverse association between BMI and EO-CRC risk in our study contradicts results from the meta-analysis [ 15 ], as well as those from the Nurses’ Health Study [ 17 ] and analyses of a large EHR database in the US [ 20 , 21 ], which reported increased risks associated with obesity. Similar to our study, a case–control study of US veterans reported an association between overweight/obesity and reduced risk of EO-CRC [ 24 ], while two other case–control studies [ 16 , 23 ] and a prospective cohort study of African American women [ 52 ] reported no associations.…”

Section: Discussionmentioning

confidence: 99%

“…Despite extensive knowledge regarding the etiology of overall CRC (based primarily on older-onset CRC) [ 14 ], there is a paucity of literature on risk factors specific to EO-CRC. A recent systematic review and meta-analysis of EO-CRC risk factors identified 20 relevant studies published up to August 2020 and reported significant associations for first-degree family history of CRC, hyperlipidemia, obesity, and alcohol consumption, although analyses for most factors were based on a small number of studies with considerable heterogeneity [ 15 ]. One of the first studies investigating EO-CRC risk factors among both men and women was a European hospital-based case–control study conducted in 1985–2009, which reported increased risk associated with family history of CRC, alcohol, and processed meat intake, and no association with physical activity, overweight/obesity, or diabetes [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Risk factors for early-onset colorectal cancer: a population-based case–control study in Ontario, Canada

Chang

Cotterchio

et al. 2021

Cancer Causes Control

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Purpose There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged < 50 years, and factors driving this upward trend are unknown. This study investigated associations between various medical, lifestyle, and dietary factors and risk of early-onset CRC (EO-CRC). Methods A population-based case–control study was conducted in Ontario, Canada during 2018–2019. EO-CRC cases aged 20–49 years (n = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (n = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47–3.84), longer sedentary time (≥ 10 vs. < 5 h/day, OR 1.93; 95% CI 1.02–3.65), greater consumption of sugary drinks (≥ 7 vs. < 1 drinks/week, OR 2.99; 95% CI 1.57–5.68), and a more Westernized dietary pattern (quartile 4 vs. 1, OR 1.92; 95% CI 1.01–3.66) were each associated with an increased risk of EO-CRC. Conversely, calcium supplement use (OR 0.53; 95% CI 0.31–0.92), history of allergy or asthma (OR 0.62; 95% CI 0.39–0.98), and greater parity in females (≥ 3 vs. nulliparity, OR 0.29; 95% CI 0.11–0.76) were each associated with a reduced risk. Conclusion Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Risk factors for early-onset colorectal cancer: a population-based case–control study in Ontario, Canada

Chang

Cotterchio

et al. 2021

Cancer Causes Control

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Synchronous Neoplasia Rates at Colonoscopic Diagnosis of Early-Onset vs Average-Onset Colorectal Cancer

2023

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ImportanceThe incidence of early-onset colorectal cancer (CRC) (age, &lt;50 years) continues to increase globally within high-income countries.ObjectiveTo examine and compare rates of synchronous neoplasia found in patients at colonoscopic diagnosis of early-onset CRC with rates found at diagnosis of average-onset CRC.Design, Setting, and ParticipantsIn this multisite retrospective and cross-sectional study conducted at Mayo Clinic sites and in the Mayo Clinic Health System from January 1, 2012, to December 31, 2022, 150 randomly selected patients with early-onset CRC were identified from the electronic health record and matched with 150 patients with average-onset CRC based on sex and colonoscopic indication. Patients with known hereditary syndromes, past history of CRC, or inflammatory bowel disease were excluded.Main Outcomes and MeasuresColonoscopic findings (polyp size, number, site) and related histopathologic findings (adenoma, advanced adenoma, sessile serrated polyp) were analyzed in association with cancer clinicopathologic features and molecular data (mismatch repair status, KRAS, and BRAFV600E).ResultsAmong 300 patients (156 men [52%]), the median age at diagnosis was 43 years (IQR, 39-47 years) for those with early-onset CRC and 67 years (IQR, 57-76) for those with average-onset CRC. Overall, 85% of patients were symptomatic at CRC diagnosis. Cancer stage, grade, molecular features, body mass index, and family history did not differ significantly between these groups. Among patients with colon cancer, the overall prevalence of synchronous neoplasia was similar, yet advanced adenomas were 3 times more frequent in those with early-onset vs average-onset cancers (31 of 75 [41%] vs 10 of 75 [13%]; P &lt; .001). This difference was not associated with cancer stage or primary location. Among patients with rectal cancer, nonadvanced adenomas were less frequent among the early-onset group than the average-onset group (21 of 75 [28%] vs 36 of 75 [48%]), and although the prevalence of advanced adenomas was similar (11 of 75 [15%] vs 14 of 75 [19%]), they were more commonly located in the rectum (early onset, 5 of 11 [45%] vs average onset, 1 of 14 [7%]). Patients with early-onset cancer of the colon were significantly more likely than those with early-onset cancer of the rectum to have a synchronous advanced adenoma (31 of 75 [41%] vs 11 of 75 [15%]; P &lt; .001).Conclusions and RelevanceIn this cross-sectional study, synchronous advanced adenomas were more commonly found in patients with early-onset colon cancer compared with average-onset colon cancer, and they were distributed throughout the colon. In contrast, advanced adenomas were not increased in patients with rectal cancer and, when detected, were predominantly located in the rectum.

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Surface‐Engineered Vanadium Carbide MXenzyme for Anti‐Inflammation and Photoenhanced Antitumor Therapy of Colon Diseases

Deng

Xian

Cai

et al. 2023

Adv Funct Materials

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The development of colitis-associated colorectal cancer is known to be associated with the inflammation-dysplasia-carcinoma pathway, and thus, chronic inflammation represents an inducer and promoter of cancer. To inhibit the evolution from colitis to colorectal cancer and provide an efficient anticancer therapy, a surface-engineered vanadium carbide MXene nanoenzyme (MXenzyme) is developed with both amino functionalization and gallium doping (Ga/V 2 C-NH 2 ). Benefiting from multiple enzymemimicking activities, MXenzymes have shown great potential to decrease excessive reactive oxygen species and inhibit the levels of proinflammatory cytokines, resulting in good anti-inflammatory effects on dextran sulfate sodium-induced acute colitis. Moreover, the gallium-doped MXene with an amino-functionalized surface can mediate improved MXene-tumor interactions and inhibitory effects on cell proliferation, achieving precise and efficient chemo-photothermal therapy. Elemental doping into MXene is also highlighted as a feasible strategy to achieve the loading and controlled release of gallium. As a result, complete tumor ablation without further recurrence is observed for the colon cancer-bearing mice that receive Ga/V 2 C-NH 2 and near infrared irradiation, while the MXenzyme system displays excellent biocompatibility at both the cellular and animal levels. These findings not only enrich the research of MXene, but also illustrate its efficient therapeutic promise in anti-inflammation and photoenhanced antitumor therapy of colon diseases.

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Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis

Cited by 191 publications

References 46 publications

Risk factors for early-onset colorectal cancer: a population-based case–control study in Ontario, Canada

Risk factors for early-onset colorectal cancer: a population-based case–control study in Ontario, Canada

Synchronous Neoplasia Rates at Colonoscopic Diagnosis of Early-Onset vs Average-Onset Colorectal Cancer

Surface‐Engineered Vanadium Carbide MXenzyme for Anti‐Inflammation and Photoenhanced Antitumor Therapy of Colon Diseases

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