Risk Factors

Risk factors for colorectal cancer (CRC) are categorized as either modifiable or nonmodifiable. Nonmodifiable risk factors include age and personal or family history of CRC. Personal or family history of CRC is considered to be associated with a high risk of developing CRC. Modifiable risk factors include many health and wellness related factors and are generally associated with an increased risk of CRC. In general, over half of all CRC is attributable to modifiable lifestyle factors.1-8,a


ASYMPTOMATIC PATIENTS ARE GENERALLY CONSIDERED TO BE AT AVERAGE RISK FOR CRC IN THE ABSENCE OF: 1-6,a

 A personal historyd of:

  • CRC, adenomatous polyps, or IBD (including Crohn’s disease and ulcerative colitis)
  • A confirmed or suspected hereditary CRC syndrome (such as familial adenomatous polyposis or Lynch syndrome)
  • Radiation to the abdomen/pelvic area to treat prior cancerb


A family history of:

  • Close relative who has had CRC or an adenomatous polyp
  • Familial adenomatous polyposis
  • Hereditary nonpolyposis CRC syndrome
~85% of patients with CRC present with comorbidities9,f

~50% of patients with CRC present with 3 or more comorbidities9,f

~29% of patients with CRC present with digestive disease10,g

~19% of patients with CRC present with diabetes10,g

Flowchart of risk factors for CRC 

  • Having a 1 or more first degree relatives with CRC is associated with an increased or high risk for the development of CRC2
    • This risk is further increased when first degree relatives with CRC are under the age of 50 years2
  • Certain factors associated with Western lifestyles are known to increase the risk of developing CRC
    • While assessment of these factors provides an important opportunity for lifestyle modification advice, their presence is not considered sufficient to elevate individuals beyond the average-risk category, and there is no evidence to support their use in stratifying subgroups of the population within the average-risk category4-6,a
  • In the United States, ~55% of all CRCs are attributable to modifiable lifestyle factors2


 Factors That Increase Risk Relative Riskd

 Hereditary and medical history

  
 Family history of CRC  

1 or more first-degree relatives

 2.2

1 or more first-degree relatives diagnosed
before age 50

 3.6

 2 or more first-degree relatives

 4.0

 1 or more second-degree relatives

1.7
 Inflammatory bowel disease 1.7
 Type 2 diabetes  

 Male

1.4

 Female

  1.2e
 Modifiable Factors  
 Heavy alcohol (daily average >3 drinks)  1.3
 Obesity (Body Mass Index ≥30 kg/m2)  1.3
 Red meat (100 g/day)  1.1
 Processed meat (50 g/day)  1.2
 Smoking  

 Current vs Never

  1.5

 Former vs Never

  1.2
 Factors that decrease risk  
 Physical activity  0.7
 Dairy (400 g/day)  0.9
  • People with a first-degree relative (parent, sibling, or child) diagnosed with CRC have 2 to 4 times the risk of developing CRC, making timely screening critical in this population.2 Both a history of a distant relative and a family history of adenomas also increase the risk of developing CRC but to a lesser degree.2
  • Obesity, inactivity, smoking, heavy alcohol use, and high consumption of red or processed meat may also be considered when estimating CRC risk for individual patients.2,6

Related Topics

CRC: Colorectal Cancer, HNPCC: Hereditary nonpolyposis CRC, SSP: Sessile Serrated Polyp, FAP: Familial Adenomatous Polyposis, IBD: Inflammatory Bowel Disease (Ulcerative Colitis, Crohn’s Disease)

References

1 PDQ Screening and Prevention Editorial Board. PDQ colorectal cancer prevention. Bethesda, MD: National Cancer Institute. Updated March 29, 2021. Accessed December 8, 2021. https://www.cancer.gov/types/colorectal/hp/colorectal-prevention-pdq

2 American Cancer Society. Colorectal cancer facts & figures 2020-2022. Atlanta: American Cancer Society; 2020.

3 Davidson KW, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325(19):1965-1977.

4 Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250-281.

5 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colorectal Cancer Screening. V.2.2021. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed February 23, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org.

6 Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017;112(7):1016-1030.

7 NCCN Clinical Practice Guidelines in Oncology - Genetic/Familial High-Risk Assessment: Colorectal (Version 1.2021). Updated May 11, 2021. Accessed December 8, 2021. https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf

8 Gupta S, Lieberman D, Anderson JS, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterol. 2020;158(4):1131-1153.e5.  

9 Hahn EE, Gould MK, Munoz-Plaza CE, et al. Understanding comorbidity profiles and their effect on treatment and survival in patients with colorectal cancer. J Natl Compr Canc Netw. 2018;16(1):23-34.

10 Fu AZ, Zhao Z, Gao S, et al. Comorbid conditions in patients with metastatic colorectal cancer. World J Oncol. 2011;2(5):225-231.

 

Footnotes

a All recommendations are category 2A unless otherwise indicated. The National Comprehensive Cancer Network (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way.

b ACS guideline excludes patients with radiation to the abdomen/ pelvic area to treat prior cancer from the average-risk category.

c Polyposis syndromes: classical familial adenomatous polyposis (FAP), attenuated FAP (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), serrated polyposis syndrome (SPS), rare genetic causes of multiple adenomatous polyps.

d Relative risk compares the risk of disease among people with a particular “exposure” to the risk among people without that exposure. Relative risk for dietary factors compares the highest with the lowest consumption. If the relative risk is more than 1.0, then risk is higher among exposed than unexposed persons. Relative risks less than 1.0 indicate a protective effect.

e Relative risk = not statistically significant.

fRetrospective, observational cohort study using longitudinal data from the Kaiser Permanente Southern California (KPSC) system. Latent class analysis (LCA) was used to identify comorbidity profiles of 7803 patients ages of 18 to 64 at diagnosis of CRC between January 1, 2008, and December 31, 2013. The EHR was used to identify treatment received and used Cox proportional hazards analysis to examine the effect of co­morbidity class on survival, as well as the effect of comorbidity profile on receipt of guideline-recommended treatment.

gThis retrospective cohort study was conducted in a population of patients 18 or older with newly diagnosed metastatic colorectal cancer (mCRC). Data was sourced from linked medical and pharmacy claims data between January 2005 and June 2008 from two US-based Medstat MarketScan claims databases. Data was analyzed for comorbid conditions and medication use in the year prior to diagnosis of mCRC. Limitations include the fact that comorbidities were identified based on healthcare service use data, thus comorbid conditions that did not trigger healthcare service use prior to diagnosis were not captured. In addition, history of smoking and obesity rates were very low, likely due to under-reporting of these two conditions in claims databases.  Univariate analyses were conducted to compare the comorbid conditions between patients aged ≥65 and <65 years old.  In total, 12,648 patients aged ≥18 years were identified. The study was evenly populated by gender and age above and below 65, and most patients had a primary diagnosis of colon cancer (70.1%).

Last Updated: 3/1/2022