History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include APC gene mutation, Lynch syndrome (hereditary non-polyposis colorectal cancer), MYH-associated polyposis, hamartomatous polyposis syndromes, inflammatory bowel disease, and obesity.

increasing age

Increasing age is the greatest risk factor for sporadic colorectal cancer. Between 2017 and 2021, the median age at diagnosis for cancer of the colon and rectum was 66 years in the US.[4]

In the US, between 2017 and 2021, more than 75% of new cases of colorectal cancer occurred in people aged >50 years.[4] However, between 1990 and 2019, there has been a significant increase in colorectal cancer incidence among adults aged <50 years, especially in developed countries.[7]​ In the US, compared with the incidence of advanced disease in 2010, a 3% annual increase in people aged <50 years and a 0.5% to 2% annual increase in people aged 50-64 years has been noted.[8]

rectal bleeding

Rectal bleeding is usually due to benign disease, but it is a common symptom in patients with colorectal cancer.[3]

One 10-year prospective study in primary care found that a new episode of rectal bleeding in patients aged >45 years had a positive predictive value for colorectal cancer of 5.7%.[146]

change in bowel habit

Increased frequency or looser stools, particularly combined with rectal bleeding, is common in left-sided cancers.

A change in bowel habit to reduced frequency and hard stools has a low predictive value for colorectal cancer.

rectal mass

There is a palpable rectal mass in 40% to 80% of patients with rectal cancer.[147][148]

Digital rectal examination to assess tumour involvement of the pelvic wall and suitability for surgery is unreliable, and this is better assessed by MRI and transrectal endoscopic ultrasound.

uncommon

positive family history

Individuals with a first-degree relative diagnosed with colorectal cancer, especially before the age of 50 years, are at increased risk for colorectal cancer.​[45][60]​​​ For individuals with one affected first-degree relative, the relative risk of developing colorectal cancer is 2.24.[16] This increases to 3.97 with two affected first-degree relatives.[16]

Family cancer syndromes, such as familial adenomatous polyposis and Lynch syndrome, are associated with 2% to 5% of all colon cancers.[18][19] However, only about 10% to 20% of patients give a family history of colorectal cancer.

abdominal mass

Usually the abdominal examination is normal. Occasionally a tumour or mass is felt, typically in advanced disease.

Other diagnostic factors

common

abdominal pain

Typically seen in colorectal cancer.​[3][149]​

anaemia

Almost 90% of patients with right-sided colon cancer have anaemia at diagnosis.​[3][150]

uncommon

male sex

Colorectal cancer is more common in men than in women.[4][8]

weight loss and anorexia

Associated with advanced disease.

abdominal distension

Indicates advanced disease due to ascites or intestinal obstruction.[3]

palpable lymph nodes

Indicates advanced disease.

Risk factors

strong

increasing age

Increasing age is the greatest risk factor for sporadic colorectal cancer. Between 2017 and 2021, the median age at diagnosis for cancer of the colon and rectum was 66 years in the US.[4]

In the US, between 2017 and 2021, more than 75% of new cases of colorectal cancer occurred in people aged >50 years.[4] However, between 1990 and 2019, there was a significant increase in colorectal cancer incidence among adults aged <50 years, especially in developed countries.[7]​ In the US, compared with the incidence of advanced disease in 2010, a 3% annual increase in people aged <50 years and a 0.5% to 2% annual increase in people aged 50-64 years has been noted.[8]​ Half of the patients who present with early-onset colorectal cancer (<50 years of age) are aged <45 years.[41]

family history

Individuals with a first-degree relative diagnosed with colorectal cancer, especially before the age of 50 years, are at increased risk for colorectal cancer.​[45][60]​​​ For individuals with one affected first-degree relative, the relative risk of developing colorectal cancer is 2.24.[16] This increases to 3.97 with two affected first-degree relatives.[16]

Siblings and children of patients with colorectal polyps are also at increased risk for developing colorectal cancer (odds ratio 1.40, 95% CI 1.35 to 1.45).[17]

adenomatous polyposis coli (APC) gene mutation

Familial adenomatous polyposis (FAP) and its variant, attenuated FAP (AFAP), are autosomal dominant diseases caused by a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5q.[49]​ Affected patients develop hundreds to thousands of adenomatous polyps by the time they are 20-30 years old and inevitably develop colorectal cancer unless they undergo prophylactic surgical resection. See Familial adenomatous polyposis syndrome.

APC mutations are frequently observed in sporadic adenomas (30% to 70%) and sporadic tumours (72%), suggesting that loss of APC function is a crucial early event in colorectal cancer tumourigenesis.

Lynch syndrome (hereditary non-polyposis colorectal cancer)

Lynch syndrome is an autosomal dominant syndrome that accounts for up to 3% of the total colorectal cancer burden.​[61][62]​​​​​ It is the most common cause of inherited colorectal cancer.[63]​ Lynch syndrome is characterised by an increased risk of developing colorectal cancer at an early age (mean age 44 years) and a high risk of extra-colonic malignancies, particularly endometrial cancer.[62] It is caused by a germline mutation in 1 of 6 DNA mismatch repair genes. These genes correct nucleotide base mispairs and small insertions or deletions that occur during DNA replication. The DNA mismatch repair (MMR) genes most commonly include hMLH1, hMSH2, hMSH6, or hPMS2.[61][64][65][66]

The mismatch repair defect promotes the development of adenomas and accelerates the progression from adenoma to carcinoma.[67] Microsatellite instability (alterations of the length of simple repetitive genomic sequences) is a hallmark of Lynch syndrome.[68]​​

MUTYH/MYH-associated polyposis

MUTYH/MYH-associated polyposis (MAP) is a recessive form of polyposis caused by mutations in both alleles of the MUTYH gene.​[49]​​​[69] The protein product of MUTYH is a glycosylase involved in excision repair of damaged DNA. Affected patients typically develop 10-100 polyps in their 40s and are at high risk for developing colorectal cancer. About one third of patients with 15-100 polyps will be found to have mutations in the MYH gene. In addition, MAP accounts for a small percentage of patients with thousands of polyps who do not have FAP.

hamartomatous polyposis syndromes

Hamartomatous polyposis syndromes are characterised by an overgrowth of cells native to the area in which they normally occur.[49] Genetic alterations are responsible for the rare inherited syndromes juvenile polyposis, PTEN hamartoma tumour syndrome (includes Cowden syndrome), and Peutz-Jeghers syndrome.[70] The latter is an autosomal dominant disorder characterised by melanocytic macules of the lips and buccal mucosa, gastrointestinal hamartomatous polyps and an increased risk of gastrointestinal and non-gastrointestinal cancers.[71] The lifetime risk of developing colorectal cancers in these patients is estimated at 39% and is thought to be due to adenomatous changes within the hamartomas.[71]

inflammatory bowel disease

Patients with ulcerative colitis and Crohn's disease are at increased risk for colorectal cancer; the risk is related to extent and duration of disease.[72][73][74] Patients with left-sided colitis, but not proctitis or proctosigmoiditis, have an increased risk but not to the same degree as patients with severe pancolitis.[75][76]

obesity

Obesity confers an increased risk of developing colon cancer and is also associated with a greater risk of dying from the disease.[20][21]​​​[22][23][24]

In one systematic review, obesity was associated with an increased risk of early-onset colorectal cancer (aged <50 years) among women.[25] While some studies have reported a significant reduction in colorectal cancer risk in patients with obesity who underwent bariatric surgery, others have failed to demonstrate a significant impact.[24][26][27][28][29]​​[30]

Obesity, high calorie intake, and physical inactivity are probably synergistic risk factors for the development of colorectal cancer.[20][22][31][32]

weak

acromegaly

Patients with acromegaly have an increased risk of colorectal cancer, although the magnitude is debated.[77]​ People with acromegaly are estimated to have twice the risk of developing colorectal cancer.​[78]

limited physical activity

There is an inverse relationship between physical activity and colon cancer (but not rectal), with a 50% reduction in those with the highest levels of activity.[32][79]

One systematic review found that physical activity reduces overall and cancer-specific mortality.[80]

lack of dietary fibre

Dietary fibre has, if anything, a weak protective effect against colorectal cancer. Most studies (but not all) suggest an inverse relationship between dietary fibre intake and colorectal cancer risk.[37][38][39][40]​​ [ Cochrane Clinical Answers logo ]

smoking

Long-term cigarette smoking is associated with increased colorectal cancer incidence and mortality.[7][47]​ Risk reduction is seen with early smoking cessation.[41][42][43]

moderate to heavy alcohol consumption

Associated with increased colorectal cancer risk.[44][45][48]

low vitamin D

Low vitamin D levels have been associated with increased colorectal cancer risk.[41][46]

consumption of red and processed meats

Studies have shown that a high intake of red and processed meat is associated with an increased risk of colorectal cancer.[33][34][35]

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