Association Between Family History and Prognosis of Patients with Colorectal Cancer: a Systematic Review and Meta-analysis

Background: A family history of colorectal cancer (CRC) increases the risk of developing CRC, and numerous studies have assessed the influence of family history on survival among CRC patients. However, the prognostic effect of a family history of CRC remains uncertain. The aim of this meta-analysis was to systematically assess the association between family history and CRC prognosis.

Methods: A comprehensive literature search was performed in the PubMed, Embase, Medline, Web of Science and Scopus databases up to October 2021, based on the Population, Intervention, Comparator, Outcomes and Study designs framework. Two reviewers independently extracted data on baseline characteristics and outcomes from the included studies. The Newcastle-Ottawa Scale was used for quality assessment of each study. Either a fixed- or a random-effects model was used to calculate the pooled hazard ratio (HR).

Results: Eighteen studies comprising 80,093 CRC patients were finally included in this meta-analysis. The Newcastle-Ottawa Scale scores of the included studies ranged from 4 to 8, and 12 studies were of high quality. A significant association between family history and improved overall survival was determined in the CRC patients (HR =0.89, 95% CI: 0.81-0.99) with significant heterogeneity (I=65.7%, P<0.001). This effect was found in male CRC patients (HR 0.70, 95% CI: 0.56-0.88) but not females (HR =0.77, 95% CI: 0.54-1.09). The association between family history and disease-free survival was not significant (HR =0.94, 95% CI: 0.88-1.01) (I=21.0%, P=0.263). However, a subgroup analysis supported the prognostic value of disease-free survival in patients with stage III CRC (pooled HR =0.78, 95% CI: 0.67-0.92).

Discussion: In conclusion, a positive family history was associated with improved overall survival in CRC patients. It was also a favorable predictor of disease-free survival in patients with stage III CRC. These findings should be interpreted with caution because of limitations related to study quality and differences in the adjusted factors across studies.