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. 2020 Aug;159(2):492-501.e7.
doi: 10.1053/j.gastro.2020.01.004. Epub 2020 Jan 9.

Risk Factors for Early-Onset Colorectal Cancer

Eric E Low  1 , Joshua Demb  2 , Lin Liu  3 , Ashley Earles  4 , Ranier Bustamante  5 , Christina D Williams  6 , Dawn Provenzale  6 , Tonya Kaltenbach  7 , Andrew J Gawron  8 , Maria Elena Martinez  9 , Samir Gupta  10
Affiliations

Risk Factors for Early-Onset Colorectal Cancer

Eric E Low et al. Gastroenterology. 2020 Aug.

Abstract

Background & aims: Colorectal cancer (CRC) incidence and mortality are increasing among persons younger than 50 years old in the United States, but risk factors associated with early-onset CRC (EOCRC) have not been widely studied.

Methods: We conducted a case-control study of US veterans 18 to 49 years old who underwent colonoscopy examinations from 1999 through 2014. EOCRC cases were identified from a national cancer registry; veterans who were free of CRC at their baseline colonoscopy through 3 years of follow-up were identified as controls. We collected data on age, sex, race/ethnicity, body weight, body mass index (BMI), diabetes, smoking status, and aspirin use. Multivariate-adjusted EOCRC odds were estimated for each factor, with corresponding 95% confidence interval (CI) values.

Results: Our final analysis included 651 EOCRC cases and 67,416 controls. Median age was 45.3 years, and 82.3% were male. Higher proportions of cases were older, male, current smokers, nonaspirin users, and had lower BMIs, compared with controls (P < .05). In adjusted analyses, increasing age and male sex were significantly associated with increased risk of EOCRC, whereas aspirin use and being overweight or obese (relative to normal BMI) were significantly associated with decreased odds of EOCRC. In post hoc analyses, weight loss of 5 kg or more within the 5-year period preceding colonoscopy was associated with higher odds of EOCRC (odds ratio 2.23; 95% CI 1.76-2.83).

Conclusions: In a case-control study of veterans, we found increasing age and male sex to be significantly associated with increased risk of EOCRC, and aspirin use to be significantly associated with decreased risk; these factors also affect risk for CRC onset after age 50. Weight loss may be an early clinical sign of EOCRC. More intense efforts are required to identify the factors that cause EOCRC and signs that can be used to identify individuals at highest risk.

Keywords: NSAID; colon cancer; epidemiology; weight loss.

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Figures

Figure 1.
Figure 1.. Early-Onset Colorectal Cancer Risk Factors.
Results of a multivariable model estimating odds for EOCRC with candidate risk factors is depicted. * Denotes statistical significance where p<0.05. All variables listed in the figure met forward stepwise selection criteria (p<0.05) and were included in the multivariable regression model. Variables selected out of the model include: (1) race/ethnicity and (2) diabetes. Hosmer-Lemeshow goodness-of-fit p-value = 0.6. EOCRC, early-onset colorectal cancer; OR, odds ratio; CI, confidence interval; BMI, body mass index.
Figure 2.
Figure 2.. Weight Trends Preceding Colonoscopy for Early-Onset Colorectal Cancer Cases and Normal Colonoscopy Controls.
Proportion of cases with ≥5 and ≥10 kg weight loss in the five year period preceding baseline colonoscopy is depicted. Differences significant at p<0.05. EOCRC, early-onset colorectal cancer; kg, kilogram.
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