31st December 2024

Colorectal cancer

Overview of colorectal cancer

This is the third most common cancer and second most common cause of cancer death in the UK. It is usually adenocarcinoma.

Approximately 25% of the population are at increased risk, including those with:

• Two or more first-degree relatives with colorectal cancer, or one if the disease was diagnosed under 55 years
• Extensive, long-standing inflammatory bowel disease
• Family history of familial adenomatous polyposis (FAP) or hereditary non-polyposis colon cancer (HNPCC), in which the inherited risk for developing colorectal cancer is autosomal dominant

Screening for colorectal cancer

In England, people aged 60-74 (50-74 in Scotland) years are invited to participate in the bowel cancer screening programme. Those aged over 74 may request screening. Eligible patients are sent a faecal immunochemical test (FIT) through the post and those with abnormal results are offered a colonoscopy. At colonoscopy, approximately:

• 5 out of 10 patients will have a normal exam
• 4 out of 10 patients will be found to have polyps
• 1 out of 10 patients will be found to have cancer

As most cancers develop from adenomatous polyps, those at increased risk of developing colorectal cancer are offered surveillance colonoscopies ranging from once a year to every five years with the aim of excising polyps if and when they are considered to have malignant potential.

Diagnosis of colorectal cancer

Colonoscopy is the first-line investigation. Double-contrast barium enema and CT colonoscopy are alternative investigations for if a patient is not fit for colonoscopy.

Once a diagnosis of colorectal cancer is made, a CT chest, abdomen and pelvis is required for staging.

CEA is a tumour marker associated with colorectal cancer. However not all tumours secrete this, and it is not specific (may be raised in conditions such as IBD). It is mainly used for disease monitoring, as levels correlate with disease burden.

Sporadic colorectal cancer

Sporadic (95%) cases of colorectal cancer develop in those with no family history as a result of a sequence of genetic mutations or deletions. It is a relatively common cancer in those over 60 years of age, with the majority of cases arising from adenomas which transform into cancer over 1-2 decades.

Resection of the primary cancer and/or limited metastasis is usually done with curative intent. Chemoradiation in addition to surgery can improve outcome in some patients

Hereditary non-polyposis colorectal carcinoma

Hereditary non-polyposis colorectal carcinoma (HNPCC, 5%), also called Lynch syndrome, is an autosomal dominant condition due to mutation in mismatch repair genes – MSH2 in 60% of cases and MLH1 in 30%. The lifetime risk of colorectal cancer is around 80%. There is also increased risk of other ‘Lynch cancers’: endometrial, ovarian, urinary tract, stomach, small bowel and hepatobiliary.

Diagnosis is suspected if there are 3 or more affected relatives (one of whom must be 1st degree) from 2 successive generations, of whom one was affected when under 50 years old. Asymptomatic relatives of patients with Lynch syndrome may be offered genetic testing.

Colonic surveillance at least every other year is advised from age 25 to 75, with the aim being early detection of Lynch syndrome-associated cancers and surgery where necessary.

Familial adenomatous polyposis

Familial adenomatous polyposis (FAP, <1%) is an autosomal dominant condition due to mutations in the APC tumour suppressor gene located on chromosome 5. It is associated with multiple colorectal adenomas, which are initially benign but likely to undergo malignant transformation. Those with FAP are also at an increased risk of developing duodenal tumours.

Diagnosis is through genetic testing of suspected individuals. Surveillance sigmoidoscopy is advised from 12 years, with prophylactic surgery usually undertaken before the age of 25 depending on the number and size of polyps and degree of dysplasia.

Gardner’s syndrome is a variant of FAP characterised by retinal pigmentation, osteomas of the skull and mandible, thyroid carcinoma, and epidermoid cysts on the skin.

Peutz-Jeghers syndrome

This is an autosomal dominant condition characterised by numerous hamartomatous polyps in the gastrointestinal tract. Malignant transformation of the polyps is rare, however around half of patients with this condition will have other gastrointestinal tract cancers (including colorectal). Peutz-Jeghers syndrome is associated with mutations in the LKB1 or STK11 genes.

Clinical features include pigmented lesions on lips, oral mucosa, face, palms and soles. Small bowel obstruction, often due to intussusception, is a common finding. Intestinal polyps can present with vomiting and abdominal pain. Symptoms of ileus, gastrointestinal bleeding, and secondary anaemia may occur as complications from the polyps.

Management is usually conservative, addressing any complications that arise.

References

• Ian B. Wilkinson et al. Oxford Handbook of Clinical Medicine. 10th ed., Oxford University Press, 2017, P. 521-527
• Lance P. Recent developments in colorectal cancer. J R Coll Physicians Lond. 1997 Sep-Oct;31(5):483-7. PMID: 9429181; PMCID: PMC5420963
• National Cancer Intelligence Network. Colorectal Cancer Survival by Stage – NCIN Data Briefing. London [Internet]: NCIN; 2009. [cited 2023 March 30]. Available from: https://www.ncin.org.uk/publications/data_briefings/colorectal_cancer_survival_by_stage.aspx
• T. Philip Chung, James W. Fleshman, The Genetics of Sporadic Colon Cancer, Seminars in Colon and Rectal Surgery [Internet], Volume 15, Issue 3,2004,Pages 128-135,ISSN 1043-1489. [cited 2023 March 30]. Available from https://doi.org/10.1053/j.scrs.2005.02.001
• DermIS Dermatology Information System, Peutz-Jeghers syndrome [Internet].  [cited 2023 March 29]. Available from https://www.dermis.net/dermisroot/en/42633/diagnose.htm
• McGarrity TJ, Amos CI, Baker MJ. Peutz-Jeghers Syndrome. 2001 Feb 23 [Updated 2021 Sep 2]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. [cited 2023 March 29]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1266/
• Carethers JM, Jung BH. Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer. [Internet]. Gastroenterology. 2015 Oct;149(5):1177-1190.e3. doi: 10.1053/j.gastro.2015.06.047. Epub 2015 Jul 26. PMID: 26216840; PMCID: PMC4589489. [cited 2023 May 22]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589489
• National Institute for Health and Care Excellence (NICE). Testing strategies for Lynch syndrome in people with endometrial cancer. 2020 [cited 2023 Aug 04]. Available from https://www.nice.org.uk/guidance/dg42/chapter/1-Recommendations