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

Hu, Yuqing LU ; Kharazmi, Elham LU ; Liang, Qunfeng LU ; Brenner, Hermann LU ; Sundquist, Jan LU ; Sundquist, Kristina LU and Fallah, Mahdi LU orcid (2025) In Cancer Communications
Abstract

Background: 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. Methods: 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. Results: We followed up... (More)

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
colorectal cancer, colorectal polyp, early-onset colorectal cancer, family history
in
Cancer Communications
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:40898381
  • scopus:105015164725
ISSN
2523-3548
DOI
10.1002/cac2.70059
language
English
LU publication?
yes
id
ae349eee-f859-497b-9ba3-d1b7c8f52cea
date added to LUP
2025-11-14 13:16:05
date last changed
2025-11-28 14:35:53
@article{ae349eee-f859-497b-9ba3-d1b7c8f52cea,
  abstract     = {{<p>Background: 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. Methods: 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. Results: 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. Conclusions: 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.</p>}},
  author       = {{Hu, Yuqing and Kharazmi, Elham and Liang, Qunfeng and Brenner, Hermann and Sundquist, Jan and Sundquist, Kristina and Fallah, Mahdi}},
  issn         = {{2523-3548}},
  keywords     = {{colorectal cancer; colorectal polyp; early-onset colorectal cancer; family history}},
  language     = {{eng}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Cancer Communications}},
  title        = {{Risk of colorectal cancer by family history of both colorectal carcinomas and colorectal polyps : a nationwide cohort study}},
  url          = {{http://dx.doi.org/10.1002/cac2.70059}},
  doi          = {{10.1002/cac2.70059}},
  year         = {{2025}},
}