What are the risk factors for colorectal cancer?

Risk Factors for Colorectal Cancer

Age is the single most important non-modifiable risk factor for colorectal cancer, with incidence rising sharply after age 50, while modifiable lifestyle factors—including smoking, obesity, physical inactivity, high red/processed meat consumption, and excessive alcohol intake—collectively account for over 50% of CRC cases and represent the most critical targets for primary prevention. 1

Non-Modifiable Risk Factors

Age and Demographics

• Age is the predominant risk factor, with nearly 70% of patients diagnosed over age 65 and 94% of new cases occurring in adults 45 years or older 2
• The median age at death from CRC is 68 years 1
• Incidence in adults aged 40-49 years has increased by almost 15% from 2000-2002 to 2014-2016, prompting earlier screening recommendations 2

Race and Ethnicity

• Black/African American individuals have the highest incidence and mortality rates of all racial groups 1
• American Indians and Alaska Natives also experience elevated disease burden 1

Family History and Genetic Factors

• Having one first-degree relative (parent, sibling, or child) with CRC increases risk 2.4-fold 2
• Two or more first-degree relatives with CRC increases risk 4.2-fold 2
• Risk is 3.8-fold higher when a first-degree relative is diagnosed before age 45, 2.2-fold for diagnosis between ages 45-59, and 1.8-fold for diagnosis at ≥59 years 2
• One first-degree relative with an adenomatous polyp increases risk approximately 2-fold 2
• Second-degree relatives (grandparents, aunts, uncles) with CRC increase risk by approximately 1.5-fold 2
• Hereditary factors account for 35% of all colon cancer cases according to large twin studies 2

Hereditary Syndromes (5-10% of all CRC)

• Familial adenomatous polyposis (FAP) and variants account for approximately 1% of CRC cases 2
• Lynch syndrome (hereditary non-polyposis colorectal cancer/HNPCC) accounts for 2-5% of CRC cases 2
• Other syndromes include Turcot, Peutz-Jeghers, and MUTYH-associated polyposis 2
• Specific genetic mutations include I1307K APC mutation in Ashkenazi Jewish populations 2

Personal Medical History

• Previous colorectal cancer or adenomatous polyps significantly increases recurrence risk 2, 3
• Inflammatory bowel disease (ulcerative colitis or Crohn's colitis) substantially increases risk, particularly 8 years after onset of pancolitis or 12-15 years after left-sided colitis 2, 1, 3
• Type 2 diabetes is associated with increased CRC risk 1
• History of abdominal or pelvic radiation for previous cancer increases risk 1
• History of acromegaly, hereditary hemochromatosis, or prior ureterosigmoidostomy also increases risk 4

Modifiable Lifestyle Risk Factors

Tobacco Use

• Cigarette smoking is a well-established risk factor for developing colorectal cancer and adenomas 2, 1, 5
• Current smokers face a relative risk of 2.17 (95% CI 1.79-2.66) compared to non-smokers 6
• The induction period between smoking exposure and cancer diagnosis is three to four decades 5
• Risk decreases with each non-smoking year after cessation 5

Body Weight and Physical Activity

• Excess body weight significantly increases CRC risk, with obese subjects having a relative risk of 1.27 (95% CI 1.06-1.53) compared to non-obese subjects 1, 6
• Physical inactivity independently contributes to CRC development, with strong positive correlation between low physical activity (measured in metabolic equivalents per week) and cancer risk (P < .001) 1, 5, 6
• Moderate regular physical activity demonstrates lower colon cancer risk, with more vigorous activity showing even greater protective benefit 5

Dietary Factors

• High consumption of red and processed meat increases risk, particularly when combined with familial risk factors 2, 1, 5, 6
• High alcohol consumption elevates CRC risk, with stronger effects when combined with familial predisposition 1, 5
• Low intake of fruits and vegetables is associated with increased risk 1, 5
• Low dietary fiber intake contributes to CRC development 1
• Low dietary calcium intake is linked to higher CRC risk 1
• High fat consumption is associated with increased risk (P < .01) 6

Geographic and Environmental Factors

• The growing incidence in historically low-risk countries reflects "westernization" including obesity, physical inactivity, heavy alcohol consumption, high red meat consumption, and smoking 2
• Migrant studies demonstrate rapid incidence increases within the first generation when moving from low-risk to high-risk areas, emphasizing the critical role of environmental and dietary factors 5

Clinical Implications and Prevention Opportunities

Approximately 50-58% of CRC cases are attributable to modifiable lifestyle factors, representing a substantial opportunity for primary prevention through behavior change 1

Key Prevention Strategies

• Smoking cessation 1
• Maintaining healthy body weight through diet and regular physical activity 1, 5
• Reducing red and processed meat consumption 1, 5
• Limiting alcohol intake 1, 5
• Increasing fruits, vegetables, fiber, and calcium intake 1, 5
• Regular physical activity 1, 5

Screening Recommendations Based on Risk

• Average-risk individuals should begin screening at age 45-50 according to updated guidelines 2, 1
• Individuals with one first-degree relative with CRC or advanced adenoma diagnosed before age 60 should begin colonoscopy at age 40 or 10 years younger than the earliest diagnosis, whichever comes first 2, 3
• Those with two or more first-degree relatives with CRC should undergo colonoscopy every 5 years, beginning at age 40 or 10 years younger than earliest diagnosis 2
• FAP gene carriers or at-risk individuals require annual sigmoidoscopy beginning at age 10-12 years 2
• Lynch syndrome gene carriers require colonoscopy every 1-2 years beginning at age 20-25 or 10 years younger than earliest family case 2
• Inflammatory bowel disease patients should begin colonoscopy 8-10 years after symptom onset, repeated every 1-3 years 3

Important Clinical Pitfalls

• Insufficient collection and utilization of family history is a major barrier to appropriate risk stratification 7
• Screening adherence is less than 50% in high-risk individuals and even lower in those under age 50 7
• In 2016,25.6% of eligible adults had never been screened, and in 2018,31.2% were not up to date with screening 2
• Provider recommendation is the most important facilitator of screening adherence 7
• Risk modification through lifestyle changes should be emphasized alongside, not instead of, regular screening according to established guidelines 5