Colorectal cancer is one of the most prevalent cancers worldwide, often beginning with small, benign polyps in the colon or rectum that can gradually turn cancerous if left untreated. Its impact is particularly severe in Singapore, where colorectal cancer ranks as the most common cancer among men and the second most common among women as per Singapore Cancer Society [1]. According to the National University Cancer Institute Singapore [2], around 1,900 new cases are diagnosed each year. This alarming rise has brought renewed attention to the importance of early detection and screening.
While lifestyle factors such as diet and physical activity contribute to colorectal cancer risk, genetics also play a crucial role. Individuals with a family history of colorectal cancer or inherited conditions like Lynch syndrome and familial adenomatous polyposis (FAP) are at significantly higher risk. However, even those without such histories can still develop the disease due to spontaneous genetic mutations. This is why regular colorectal screenings, such as colonoscopies, are vital for early detection.
In this article, we will explore how genetic predispositions can increase the risk of colorectal cancer and why getting screened regularly is critical for everyone, regardless of family history. Early screening can help detect polyps before they turn into cancer, and offer a powerful preventive measure against this growing health threat.
Colorectal cancer is a type of cancer that starts in the colon or rectum, often developing from benign polyps that can turn cancerous over time.
How Does Genetics Increase Your Risk for Colorectal Cancer?
Genetics play a significant role in increasing the risk of colorectal cancer, particularly through inherited syndromes such as Lynch syndrome and familial adenomatous polyposis (FAP). These genetic conditions drastically elevate an individual’s likelihood of developing colorectal cancer and are passed down hereditarily;
- Lynch Syndrome: also known as hereditary nonpolyposis colorectal cancer (HNPCC), is the most common hereditary colorectal cancer syndrome [3]. Individuals with Lynch syndrome inherit mutations in genes responsible for repairing DNA errors, such as MLH1, MSH2, MSH6, PMS2, and EPCAM [4]. These mutations prevent the body from correcting errors in DNA, leading to the growth of abnormal cells, which can become cancerous. According to the American Cancer Society [5], those with Lynch syndrome may develop colorectal cancer at a younger age, often before the age of 50. Additionally, Lynch syndrome increases the risk of other cancers, including endometrial, ovarian, and stomach cancer.
- Familial adenomatous polyposis (FAP): another genetic condition associated with a heightened risk of colorectal cancer [6]. This syndrome is caused by mutations in the APC gene, a tumour suppressor gene that normally helps control cell growth. In individuals with FAP, hundreds to thousands of polyps can form in the colon and rectum, with nearly all affected individuals developing colorectal cancer if the polyps are not removed early. FAP is typically diagnosed in adolescence or early adulthood, and early intervention through screening and surgery is crucial in reducing cancer risk.
It is important to note that even those without a family history of colorectal cancer can develop the disease due to spontaneous genetic mutations. Research shows that up to 10% of colorectal cancer [7] cases have a genetic component, even in patients with no apparent family history. This highlights the importance of regular screenings for early detection, regardless of family history.
Can Lifestyle Choices Lower Your Risk of Colorectal Cancer Despite Genetic Predispositions?
While genetics can significantly increase your risk of colorectal cancer, lifestyle factors also play a crucial role in determining your overall risk. Even individuals with a genetic predisposition can make lifestyle choices that may reduce the likelihood of developing this disease. Below are the key lifestyle factors that influence colorectal cancer risk:
- Diet: A diet high in red and processed meats has been strongly associated with an increased risk of colorectal cancer. Studies have shown [8] that consuming large amounts of processed meats like bacon, sausages, and deli meats can heighten the chances of developing cancer due to the carcinogens released during processing and cooking at high temperatures. On the other hand, diets rich in fruits, vegetables, and fibre can have a protective effect. Fibre promotes healthy digestion and supports gut health, which can reduce the risk of polyps turning into cancerous growths.
- Physical Activity: Regular exercise has been consistently linked to a lower risk of colorectal cancer. Physical activity helps regulate hormone levels, reduces inflammation, and aids in maintaining a healthy weight—all factors that lower cancer risk. For those with a genetic predisposition, staying physically active may mitigate some of the increased risk posed by genetic factors.
- Smoking and Alcohol: Smoking and heavy alcohol consumption [9] are well-established risk factors for colorectal cancer. Smoking introduces harmful carcinogens that affect the entire body, including the colon, while excessive alcohol intake is associated with damage to the lining of the digestive system, which can increase cancer risk. Limiting alcohol and quitting smoking can significantly reduce your overall risk, even for those genetically predisposed.
While genetic factors like Lynch syndrome and familial adenomatous polyposis (FAP) may increase your susceptibility to colorectal cancer, adopting a healthy lifestyle can help reduce the overall risk. Maintaining a balanced diet, exercising regularly, and avoiding harmful habits like smoking and excessive drinking can not only improve your general health but also play a role in preventing the development of cancerous polyps in those already genetically predisposed.
Should You Get Tested?
When it comes to colorectal cancer, early detection is critical. For individuals with a family history of the disease or known genetic conditions such as Lynch syndrome or familial adenomatous polyposis (FAP), getting tested early can make a significant difference in prevention and treatment outcomes. But what types of tests are available, and which should you consider?
The Importance of Genetic Screening and Colonoscopy
Genetic screening plays a key role in identifying people at higher risk of colorectal cancer, especially for those with hereditary syndromes. While specific genetic tests such as those for Lynch syndrome (testing mutations in genes like MLH1, MSH2, MSH6, and PMS2) or FAP (APC gene mutations) can help assess risk, genetic testing alone isn’t enough. Regular screening methods, especially colonoscopy, remain essential even if you have a known genetic predisposition.
Colonoscopy– The Gold Standard for Colorectal Screening
Colonoscopy is the most effective screening method for detecting colorectal cancer early. During the procedure, a doctor can directly visualise the colon and rectum, which can help them identify precancerous polyps before they can develop into cancer. For those with hereditary cancer syndromes, the recommended age to begin colonoscopy screenings is significantly earlier than for the average population. Typically, individuals with genetic risks should start screening in their 20s or 30s [10], compared to the general recommendation of age 45 for people without a family history. Moreover, they may need to undergo colonoscopies every 1-2 years, rather than the standard 10-year interval, ensuring that any abnormalities are caught as early as possible.
Another benefit of colonoscopies is that they not only detect cancer but also offer an opportunity for polyp removal during the procedure. For those with FAP, where hundreds of polyps can develop in the colon, regular removal can dramatically reduce the risk of anyone polyp turning cancerous. This preventive aspect of colonoscopy is crucial for individuals with a high genetic risk.
If you have a family history of colorectal cancer or are concerned about your risk, combining genetic screening with regular colonoscopy offers the best approach for early detection and prevention. Consulting your healthcare provider about when to start and how often to be screened could save your life.
Tests like colonoscopy can help detect colorectal cancer early, especially for individuals with a genetic risk, by identifying and removing precancerous polyps before they develop into cancer.
How Does Genetic Testing Influence Colorectal Cancer Treatment?
Genetic testing plays a critical role in shaping the treatment approach for colorectal cancer. By identifying specific gene mutations, healthcare providers can tailor treatments to target the cancer more effectively, which can help improve outcomes and minimise unnecessary side effects.
- Personalised Treatment Plans: Genetic testing can reveal mutations in genes such as KRAS, NRAS, and BRAF, which influence how a tumour grows and responds to treatment. For example, mutations in the KRAS gene [11] indicate that certain targeted therapies, such as EGFR inhibitors, will not be effective. Knowing these genetic details helps oncologists choose the most effective drugs from the start, avoiding trial-and-error approaches to treatment.
- Immunotherapy: Patients with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumours, commonly seen in those with Lynch syndrome, often respond well to immunotherapy [12]. This form of treatment helps the body’s immune system recognise and attack cancer cells, and it has shown remarkable success in improving survival rates for patients with specific genetic markers.
- Chemotherapy and Targeted Therapy Adjustments: Genetic testing results may also influence the use of chemotherapy and targeted therapies. For instance, patients with BRAF mutations are often treated with combinations of targeted therapies and chemotherapy [13] to improve their response rates. Furthermore, identifying HER2 overexpression in some colorectal cancer patients [14] can lead to the use of HER2-targeted therapies, which have shown promise in treating advanced cases.
- Family Risk Assessment: Beyond guiding treatment, genetic testing can help assess the cancer risk in family members. If a mutation such as APC (linked to familial adenomatous polyposis) or MLH1 (associated with Lynch syndrome) is detected, family members may be encouraged to undergo genetic counseling and early screening, which can lead to timely preventive measures.
Conclusion: Take Charge of Your Health—Don’t Delay Screening
Colorectal cancer is a silent threat, often progressing without symptoms until it’s too late. While genetic factors like Lynch syndrome and familial adenomatous polyposis (FAP) can significantly increase your risk, early detection through regular screenings such as colonoscopies offers a powerful defence. For those with a family history or known genetic predisposition, starting screening early and undergoing frequent colonoscopies could be the difference between life and death.
Regular colonoscopies not only catch colorectal cancer in its early stages but also allow for the removal of precancerous polyps, preventing cancer from developing in the first place. Whether you’ve tested positive for hereditary cancer syndrome or are simply concerned about your family history, don’t wait until symptoms appear—take action now.
At Ark Surgical Practices Singapore, we offer comprehensive colorectal cancer screening services, personalised to your individual needs. Schedule your colonoscopy today and take a proactive step toward safeguarding your health.
References
- Singapore Cancer Society.
https://www.singaporecancersociety.org.sg/knowcancertobeatcancer/component/content/articl e/10-colorectal/75-does-colorectal-cancer-only-affect-men-mostly. Accessed 13 Sept. 2024.
- Colorectal Cancer – NCIS | National University Cancer Institute, Singapore.
https://www.ncis.com.sg/Cancer-Information/About-Cancer/Pages/Colorectal-Cancer.aspx. Accessed 13 Sept. 2024.
- Steinke, Verena, et al. “Hereditary Nonpolyposis Colorectal Cancer (HNPCC)/Lynch Syndrome.” Deutsches Ärzteblatt International, vol. 110, no. 3, Jan. 2013, pp. 32–38. PubMed Central, https://doi.org/10.3238/arztebl.2013.0032.
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- Lynch Syndrome.
https://www.cancer.org/cancer/risk-prevention/genetics/family-cancer-syndromes/lynch-syndro me.html. Accessed 13 Sept. 2024.
- Menon, Gopal, et al. “Familial Adenomatous Polyposis.” StatPearls, StatPearls Publishing, 2024. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK538233/.
- Hereditary Colon Cancer: Guide for Health Pros | Guide to Hereditary Cancer for Health Pros | UT Southwestern Medical Center.
http://utswmed.org/conditions-treatments/genetics-and-hereditary-cancers/guide-hereditary-c ancer-health-pros/hereditary-colon-cancer-guide-health-pros/. Accessed 13 Sept. 2024.
- Santarelli, Raphaëlle L., et al. “Processed Meat and Colorectal Cancer: A Review of Epidemiologic and Experimental Evidence.” Nutrition and Cancer, vol. 60, no. 2, 2008, pp. 131–44. PubMed Central, https://doi.org/10.1080/01635580701684872.
- Amitay, Efrat L., et al. “Smoking, Alcohol Consumption and Colorectal Cancer Risk by Molecular Pathological Subtypes and Pathways.” British Journal of Cancer, vol. 122, no. 11, May 2020, pp. 1604–10. PubMed Central, https://doi.org/10.1038/s41416-020-0803-0.
- Wilkinson, Anna N., et al. “Colorectal Cancer Screening for Patients with a Family History of Colorectal Cancer or Adenomas.” Canadian Family Physician, vol. 65, no. 11, Nov. 2019, pp. 784–89. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853346/.
- “KRAS Mutation.” Testing.Com, 15 Nov. 2019, https://www.testing.com/tests/kras-mutation/.
- Mulet-Margalef, Núria, et al. “Challenges and Therapeutic Opportunities in the dMMR/MSI-H Colorectal Cancer Landscape.” Cancers, vol. 15, no. 4, Feb. 2023, p. 1022. PubMed Central, https://doi.org/10.3390/cancers15041022.
- Martinelli, E., et al. “Real-World First-Line Treatment of Patients with BRAFV600E-Mutant Metastatic Colorectal Cancer: The CAPSTAN CRC Study.” ESMO Open, vol. 7, no. 6, Nov. 2022, p. 100603. PubMed Central, https://doi.org/10.1016/j.esmoop.2022.100603.
- HER2 in colorectal cancer: guidance for pathologists receiving requests for testing. The Royal College of Pathologists.