Family history of colorectal polyps and risk of colorectal cancer
A Swedish nationwide case-control study assessed the risk of colorectal cancer (CRC) in first degree relatives (parents and full siblings) of patients with precursor lesions (polyps) for CRC (1)
Participants 68060 patients with CRC and 333753 matched controls
Main outcome measures Multivariable adjusted odds ratios of CRC according to the number of first degree relatives with a colorectal polyp and the histology of polyps and age at diagnosis in first degree relatives. Subgroup analysis was also performed according to age at CRC diagnosis and evaluated the joint association of family history of colorectal polyps and family history of CRC
Results
- after adjusting for family history of CRC and other covariates, having a first degree relative with a colorectal polyp (8.4% (5742/68060) in cases and 5.7% (18860/333753) in controls) was associated with a higher risk of CRC (odds ratio 1.40, 95% confidence interval 1.35 to 1.45)
- odds ratios ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas
- association between family history of polyps and CRC risk was strengthened by the increasing number of first degree relatives with polyps (>=2 first degree relatives: 1.70, 1.52 to 1.90, P<0.001 for trend) and decreasing age at polyp diagnosis (<50 years: 1.77, 1.57 to 1.99, P<0.001 for trend)
- a particularly strong association was found for early onset CRC diagnosed before age 50 years (>=2 first degree relatives: 3.34, 2.05 to 5.43, P=0.002 for heterogeneity by age of CRC diagnosis
- odds ratio of CRC for individuals
- with two or more first degree relatives with polyps but no CRC was 1.79 (1.52 to 2.10)
- with one first degree relative with CRC but no polyps was 1.70 (1.65 to 1.76)
- with two or more first degree relatives with both polyps and CRC was 5.00 (3.77 to 6.63) (P<0.001 for interaction)
Main findings:
- individuals with at least two first degree relatives with polyps or a first degree relative with polyps diagnosed at a young age, most of whom are not yet recommended for early screening according to existing guidelines, are at an increased risk of CRC, particularly early onset disease, and they might benefit from early screening
- compared with the advanced histology of polyps, the higher number of first degree relatives with polyps and younger age at polyp diagnosis seemed to be more predictive of CRC risk in family members
Note
For individuals with one affected first-degree relative, the relative risk of developing colorectal cancer is 2.24. (2)
This increases to 3.97 with two affected first-degree relatives. (2)
Family cancer syndromes, such as familial adenomatous polyposis (FAP) and Lynch syndrome, are associated with 2% to 5% of all colon cancers. (3)
References:
- Song M, Emilsson L, Roelstraete B, Ludvigsson J F. Risk of colorectal cancer in first degree relatives of patients with colorectal polyps: nationwide case-control study in Sweden BMJ 2021; 373 :n877 doi:10.1136/bmj.n877
- Butterworth AS, Higgins JP, Pharoah P. Relative and absolute risk of colorectal cancer for individuals with a family history: a meta-analysis. Eur J Cancer. 2006 Jan;42(2):216-27.
- Ma H, Brosens LA, Offerhaus GJ, et al. Pathology and genetics of hereditary colorectal cancer. Pathology. 2017 Nov 21;50(1):49-59.