# Risk of colorectal cancer by family history of both colorectal carcinomas and colorectal polyps: a nationwide cohort study

## TL;DR

People with a family history of both colorectal polyps and cancer have a much higher risk of developing colorectal cancer, especially at a younger age.

## Contribution

This study is the first to quantify the increased risk of colorectal cancer from family history of both polyps and carcinomas.

## Key findings

- Individuals with one first-degree relative with a polyp and another with cancer had a 2.2 times higher CRC risk.
- Those with repeated polyp diagnoses and a family history of cancer had a 5.4 times higher early-onset CRC risk.
- More relatives with polyps and cancer, and younger age at diagnosis, were linked to higher CRC risk.

## Abstract

The increased risk of colorectal cancer (CRC) associated with family history of both colorectal in situ or invasive carcinomas (Stage 0 to IV) and colorectal polyps is attributed solely to family history of CRC, resulting in an underestimation of the actual risk. We aimed to assess the association between overall and early‐onset CRC (EOCRC) risk and family history of both colorectal carcinomas and polyps.

We conducted a nationwide cohort study leveraging Swedish family‐cancer datasets with follow‐up from 1964 to 2018. Standardized incidence ratios (SIRs) were calculated to estimate the risk of CRC and EOCRC among individuals with a family history of both colorectal polyps and carcinomas.

We followed up 13,432,205 individuals for up to 54 years. The risk of overall CRC was 2.2 times increased in individuals with 1 first‐degree relative (FDR) with one‐time polyp diagnosis and an additional FDR with carcinoma (95% CI = 2.1‐2.3; EOCRC SIR = 2.9 [95% CI = 2.4‐3.4]). The risk was significantly higher in individuals with 1 FDR with repeated polyp diagnoses (≥2 times) and an additional FDR with carcinoma (overall SIR = 2.9 [95% CI = 2.7‐3.1]; EOCRC SIR = 5.4 [95% CI = 3.9‐6.4]). A similar risk was observed in individuals with ≥2 FDRs with one‐time polyp diagnosis and an additional FDR with carcinoma (overall SIR = 2.9 [95% CI = 2.4‐3.4]; EOCRC SIR = 5.3 [95% CI = 3.0‐8.6]). Individuals with ≥2 FDRs with repeated polyp diagnoses and an additional FDR with carcinoma had a 5.0‐fold overall risk (95% CI = 4.3‐5.7) and a 13.8‐fold EOCRC risk (95% CI = 9.7‐20.1). Younger age at polyp/carcinoma diagnoses, and more relatives with polyps and carcinomas were associated with higher CRC risk.

Individuals with a family history of both colorectal polyps and carcinomas are at significantly increased risk of CRC, especially EOCRC. The risk increased with frequent polyp diagnoses, younger age at first polyp/carcinoma diagnoses, and the number of relatives with polyps/carcinomas. This study highlights the importance of considering both colorectal polyps and carcinomas in family history when assessing CRC risk. These findings could supplement current screening guidelines.