Abstract
Obesity is associated with increased risk of colorectal cancer (CRC) and a more aggressive disease course. Tumor budding (TB) is an important prognostic factor for CRC, but its association with obesity is unknown. To evaluate the association of TB with obesity and other prognostic factors in colon cancer. This cohort study involved a histological review of colon cancer specimens obtained during 7 years (January 2008 to December 2015) at the University of Kentucky Medical Center; data analysis was conducted from February 2020 to January 2021. Specimens came from 200 patients with stage I to III colon cancer; patients with stage 0, stage IV, or incomplete data were excluded. TB was defined as 1 to 4 malignant cells at the invasive edge of the tumor, independently assessed by 2 academic pathologists. The primary outcome was the association of TB with obesity (defined as body mass index [BMI] of 30 or greater). Secondary outcomes include the association of TB with clinical features (ie, age, race, sex, TNM stage, tumor location) and pathological features (ie, poorly differentiated tumor clusters [PDCs], Klintrup-Mäkinen inflammatory score, desmoplasia, infiltrative tumor border, tumor necrosis, and tumor-to-stroma ratio). A total of 200 specimens were reviewed. The median (interquartile range) age of patients was 62 (55-72) years, 102 (51.0%) were women, and the mean (SD) BMI was 28.5 (8.4). A total of 57 specimens (28.5%) were from stage I tumors; 74 (37.0%), stage II; and 69 (34.5%), stage III. Of these, 97 (48.5%) had low-grade (<5 buds), 36 (18.0%) had intermediate-grade (5-9 buds), and 67 (33.5%) had high-grade (≥10 buds) TB. Multivariable analysis adjusting for clinical and histological factors demonstrated that higher TB grade was associated with obesity (odds ratio [OR], 4.25; 95% CI, 1.95-9.26), higher PDC grade (grade 2 vs 1: OR, 9.14; 95% CI, 3.49-23.93; grade 3 vs 1: OR, 5.10; 95% CI, 2.30-11.27), increased infiltrative tumor border (OR, 1.03; 95% CI, 1.01-1.04), cecal location (OR, 2.55; 95% CI, 1.09-5.97), and higher stage (eg, stage III vs stage I for high-grade or intermediate-grade vs low-grade TB: OR, 2.91; 95% CI, 1.00-8.49). Additionally, patients with a higher TB grade had worse overall survival (intermediate vs low TB: hazard ratio, 2.20; 95% CI, 1.11-4.35; log-rank P = .02; high vs low TB: hazard ratio, 2.67; 95% CI, 1.45-4.90; log-rank P < .001). In this cohort study, a novel association between high TB grade and obesity was found. The association could reflect a systemic condition (ie, obesity) locally influencing aggressive growth (ie, high TB) in colon cancer.
Highlights
Colorectal cancer (CRC) remains the second most common cause of cancer deaths in the United States
Multivariable analysis adjusting for clinical and histological factors demonstrated that higher Tumor budding (TB) grade was associated with obesity, higher poorly differentiated tumor clusters (PDCs) grade, increased infiltrative tumor border (OR, 1.03; 95% CI, 1.01-1.04), cecal location (OR, 2.55; 95% CI, 1.09-5.97), and higher stage
We found that colon cancer samples with higher grades of TB were more than twice as likely to come from a patient with obesity, further reinforcing the role that obesity plays in early-onset colon cancer
Summary
Colorectal cancer (CRC) remains the second most common cause of cancer deaths in the United States. 52 980 people in the United States will die from CRC in 2021. The incidence among those older than 65 years has been steadily declining.[1] the incidence in those aged between 50 to 64 years has been increasing by 1% annually, and that among patients younger than 50 years has been increasing by 2% annually. Mortality rates have increased by 1.3% annually in those younger than 50 years.[1,2,3] Modifiable factors for CRC include tobacco exposure, alcohol consumption, poor diet, and obesity; these are major contributors to the increased incidence and mortality.[4]
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