Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer

Abstract

Background Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Methods Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Results Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P = .04). Conclusion In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.

The Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review

“…Agazzi and colleagues demonstrated that the smoking status was not significantly associated with either the presence of adenomas or eoCRC in a 2021 study, even accounting for bias related to pooling of eoCRC and adenomas cases [117]. In line with this, no statistically significant differences were observed between eoCRCs and healthy age and sex-matched controls in pack/year smoking among current and former smokers in the above-discussed report by Archambault et al [57]. In a 2020 single-center retrospective observational study on a small sample of 48 advanced colorectal neoplasia, Krigel et al also failed to demonstrate smoking status as a risk factor for eoCRC [118].…”

“…While consistent data are available on exogenous risk factors involved in loCRC pathogenesis, to date, the corresponding studies on eoCRCs’ populations are still scant, particularly regarding dietary risk factors and physical activity. Indeed, few studies have investigated diet [ 29 , 33 , 37 , 57 , 58 , 59 , 65 ] and physical activity [ 27 , 28 , 29 , 37 , 57 , 59 , 96 ] as risk factors involved in the pathogenesis of eoCRC and its precursors, with contrasting results. The literature published so far on the role of diet, alcohol, and physical activity involved in eoCRC pathogenesis consists mostly of retrospective and observational studies with evident heterogeneity.…”

“…Similarly, the pooled analysis by Archambault et al [ 57 ] suggests that eoCRC may be significantly associated with heavier alcohol use (>28 g/day of alcohol; OR 1.25). It is interesting to note that the authors also found a significant increase in the risk of eoCRC with alcohol abstinence (OR 1.23).…”

“…Archambault and colleagues recently pooled and analyzed data from 13 population-based studies, including 3767 eoCRCs and 4049 age- and sex-matched controls, via multivariable and multinomial logistic regression for association with several risk factors [ 57 ]. The results showed that eoCRC may be significantly associated with greater red meat intake (OR 1.10).…”

“…Despite these reports linking physical activity (or lack thereof) to eoCRC, an approximately equal weight of evidence to the contrary exists at present. Archambault and colleagues [ 57 ] found no difference in eoCRC with sedentary lifestyle defined as <1 h/w of moderate/vigorous physical activity, leisure time, and undifferentiated activities. The 2008 multi-center retrospective case–control study by Imperiale and colleagues [ 37 ] failed to identify an association between eoCRC and physical activity, defined as regular exercise, even if not further specified.…”