The obesity paradox in patients with colorectal cancer: a systematic review and meta-analysis

Obesity is widely regarded as an established risk factor for colorectal cancer (CRC). However, recent studies have shown that lower mortality and better cancer-specific survival were observed in CRC patients with elevated body mass index (BMI), an example of the obesity paradox, which is the inverse correlation between obesity and mortality in some populations.The aim of this systematic review and meta-analysis was to investigate the association between BMI and CRC outcomes.PubMed, Web of Science, MEDLINE, the Cochrane Library, and Embase databases were searched for relevant articles published from inception to December 31, 2020.Studies comparing the prognosis of CRC patients with obesity or overweight with that of normal-weight CRC patients were eligible.Data were extracted by 2 reviewers independently; differences were resolved by a third reviewer. BMI was classified according to WHO categories.To assess the prognostic effects of different BMI categories in CRC patients, hazard ratios and 95%CIs of overall survival, disease-free survival, and cancer-specific survival were extracted from included articles.Sixteen studies (55 391 patients in total) were included. Higher BMI was significantly associated with more favorable CRC outcomes. Compared with normal-weight patients, underweight patients had worse overall survival (HR = 1.26; 95%CI, 1.15-1.37) and disease-free survival (HR = 1.19; 95%CI, 1.11-1.27, while patients with overweight had better overall survival (HR = 0.92; 95%CI, 0.86-0.99), disease-free survival (HR = 0.96; 95%CI, 0.93-1.00), and cancer-specific survival (HR = 0.86; 95%CI, 0.76-0.98). Patients with morbid obesity had worse overall survival (HR = 1.12; 95%CI, 1.02-1.22) and disease-free survival (HR = 1.15; 95%CI, 1.07-1.24) than normal-weight patients. There was no significant difference in cancer-specific survival between patients with obesity (HR = 0.94; 95%CI, 0.76-1.16) and patients with normal weight, nor between patients with underweight and patients with normal weight (HR = 1.14; 95%CI, 0.82-1.58).CRC patients with a higher BMI appear to have reduced mortality compared with normal-weight CRC patients, even though higher BMI/obesity is an established determinant for the development of CRC.PROSPERO registration no. CRD42020202320.