Ahvaz Jundishapur University of Medical Sciences, Iran (Islamic Republic of)
Colorectal cancer is the second leading cause of morality worldwide, representing a significant indicator for evaluating global cancer patterns and trends.[1, 2] Colorectal cancer is also the third most common malignancy worldwide, ranking third among men and second among women, thereby emerging as a major global health concern.[1, 3]
Factors such as population characteristics, community behavior, and environmental interactions that increase the risk of colorectal cancer.[4] The Human Development Index (HDI) plays a significant role in this context, as developed countries, due to lifestyle patterns, dietary habits, and nutritional diversity, report the highest increasingly exposed to rising colorectal cancer rates as a result of urbanization and Westernization. A common feature shared by both groups of societies is the rising trend of colorectal cancer incidence.[1]
Colorectal cancer is defined by the rapid and uncontrolled proliferation of cells in the colon and rectum, with the potential to metastasize and spread to other tissues throughout the body.[5] The colon and rectum do not share the same embryonic origin and anatomical differences.[5]
The occurrence of colorectal cancer is influenced by non-modifiable factors such as age, genetics and sex, as well as modifiable, environment-related factors.[6] Non-modifiable factors are generally immutable; however, identifying these factors is crucial for screening high-risk individuals and preventing the onset of colorectal cancer.[7]
For each individual, the probability of developing colorectal cancer varies according to their lifestyle.[6] Key factors such as obesity, smoking, alcohol consumption, high-fat diets, red meat intake, family history, physical activity levels, and hormone replacement therapy increase the
risk of developing colorectal cancer.[1, 5] Inflammatory diseases also play a role in increasing the risk of colorectal cancer.[6] Although colorectal cancer can occur at younger ages, its incidence is significantly higher after the age of 50, with statistics indicating that 9 out of 10 diagnosed cases are over 50 years old.[6] The probability of developing colorectal cancer is estimated at 60% in men and 40% in women.[6, 8]
Regular physical activity contributes to a 20-30% reduction in the risk of colorectal cancer.[9] Maintaining the balance of the gut microbiome is effective in preventing this type of cancer.[9, 10] There are two main approaches to prevention: primary prevention, which involves avoiding risk factors, and secondary prevention, which includes screening for the identification of precancerous conditions.[9, 11]
Materials and Methods:
To retrieve published studies and identify relevant articles, we conducted a comprehensive
search across multiple databases, including Medline, Embase, Iran Medex and Google Scholar. Systematic reviews published in English from 2015 to the most recent studies were included. Regarding the search criteria, we utilized Medical Subject Headings (Mesh) such as colorectal cancer, risk factors, screening and epidemiological studies to retrieve relevant evidence. A
thorough review of the full text of the retrieved articles was performed for this study. In addition, the reference lists of the included articles were examined to identify any additional relevant sources within the same field.
Results:
In this section, modifiable and non-modifiable risk factors, as described in the previous section, are examined separately:
Non-modifiable risk factors:
1. Age: Data obtained from various studies indicate that the likelihood of developing colorectal cancer is up to 3.5 times higher in individuals over 50 years of age compared to those below this age group (approximately 70% of colorectal cancer patients are over 50 years old). More
detailed analyses show that the majority of colorectal cancer cases occur in the 60-79 year age range.[6] In fact, the risk of developing colorectal cancer rises sharply during the sixth decade of life, which is why preventive screenings are often recommended during this age range.[11] Colonoscopy studies indicate that the likelihood detecting colorectal polyps increases with age, with these polyps being more frequently observed in individuals over 69 years old.[8] Colorectal cancer can also occur in individuals under 40 years of age; however such cases are reported to be rare.[6] Notably, 16% of colorectal cancers diagnosed before the age of 50 are attributed to a hereditary syndrome.[10]
2. Medical History: The reduction in colorectal cancer mortality depends not only on treatment strategies but also on early primary diagnoses, detection at initial cancer stages, and the removal of high-risk polyps.[10] Certain diseases increase the likelihood of developing colorectal cancer; for example, neoplastic polyps of the colon are considered precancerous lesions and important risk factors for colorectal cancer.[6] Individuals with conditions such as cystic fibrosis, kidney transplantation, cholecystectomy, coronary artery disease and gastrointestinal bacterial or viral infections are at a higher risk of developing colorectal cancer.[9] Since colorectal adenomas play a critical role in the development and progression of colorectal cancer, their early detection and treatment are of great importance.[12] The presence of colonic adenomas significantly increases the risk of developing colorectal cancer, with approximately 95% of sporadic cases arising from adenomas.[6] Studies in patients with colorectal cancer have shown that the presence of diabetes increases the risk of developing this disease by up to 38%.[6] Epidemiological studies over the past two decades have demonstrated a clear association between Parkinson’s disease and colorectal cancer.[13] In contrast to the aforementioned factors that increase the risk of colorectal cancer, conditions such as asthma and allergies, calcium supplementation, and higher parity in women are associated with a reduced likelihood of developing the disease.[14] Several syndromes have been identified as risk factors for colorectal cancer, including hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), Muir-Torre syndrome, Turcot syndrome, polymorphisms, attenuated familial adenomatous polyposis(AFAP), Peutz-Jeghers syndrome, juvenile polyposis, and hamartoma Tous tumor syndromes.[15] A history of radiotherapy in the abdominal and pelvic regions can increase the risk of developing colorectal cancer.[9]
modifiable risk factors:
1. obesity: In individuals with obesity and a high body mass index (BMI), the risk of developing colorectal cancer is elevated.[6] Comparative data indicate that individuals with a BMI<30 have a 5% to 100% higher risk of developing colorectal cancer compared to those with a BMI>23.[6] Excessive overweight, physical inactivity, and lack of regular exercise contribute to an increased risk of colorectal cancer.[6] Individuals leading a sedentary lifestyle have up to a 50% higher risk of developing colorectal cancer.[6, 9] For every 5kg increase in body weight, particularly in men, the risk of developing colorectal cancer rises by 3%.[6]
2. Diet: Diet is a significant environmental factor in the development of colorectal cancer. High- fat foods, particularly those rich in animal fats, cooking methods at high temperatures, and low- fruit diets increase the risk of colorectal cancer.[6] Consumption of dairy products is associated with a reduced risk of colorectal cancer, such that individuals who consume 400g of dairy products or 200g of milk daily may reduce this risk by up to 10%.[9] Each 10g increase in dietary fiber intake reduces the risk of colorectal cancer by 10%.[9] Since low vitamin D intake is associated with an increased risk of this cancer, the combined intake of calcium and vitamin D plays a protective role in its prevention.[6, 9]
3. Smoking and Alcohol Consumption: While smoking does not directly cause colorectal cancer, it significantly increases the risk of its development.[6] Heavy smoking has been shown to
markedly elevate the risk of early-onset colorectal neoplasms, both of which are recognized as independent risk factors for colorectal cancer.[12] Smoking cessation can reduce this risk by up
to 50%.[9] Overall, alcohol consumption is also associated with an increased risk of colorectal cancer; however, the pattern and level of alcohol intake may influence the magnitude of this risk.[6]
4. Hormonal Levels: Evidence from animal studies indicates that elevated levels of cortisol, epinephrine, and norepinephrine contribute to the initiation of carcinogenesis.[9] High
occupational stress is also associated with an increased risk of colorectal cancer, as stress induces abnormal metabolic activity and negatively impacts tumorigenesis, for instance by promoting genomic instability or enhancing metastatic factors such as angiogenesis.[9, 14] In women, oral contraceptives before menopause and postmenopausal hormone replacement therapy with estrogen and progesterone appear to exert protective effects against colorectal cancer.[9]
Consequently, regulation and control of these hormonal factors may reduce the risk of colorectal cancer.
Conclusion:
Based on the findings of the present review and the identification of risk factors that increase the likelihood of colorectal cancer, it is possible to reduce the incidence of this disease through preventive approaches. Overall, lifestyle modification plays a pivotal role in lowering the risk. Effective strategies in this regard include mandatory screening for individual with a family history and those over 50 years of age, identifying high-risk individuals and tailoring their diets with emphasis on adequate intake of vitamins-particularly vitamin D-fiber, and dairy products, as well as establishing task forces aimed at encouraging at-risk age groups to engage in regular physical activity and reduce sedentary behavior in daily life.
References:
1. Matsuda, T., A. Fujimoto, and Y. Igarashi, Colorectal Cancer: Epidemiology, Risk Factors, and Public Health Strategies. Digestion, 2025.
2. Darbandi, M., et al., A comparison of the burden of cancers between 1990 and 2019 in Iran: A national and subnational study. PloS one, 2025. 20(2): p. e0309699.
3. Rezaianzadeh, A., et al., A systematic review over the incidence of colorectal cancer in Iran. Iranian Journal of Colorectal Research, 2015. 3(1): p. 0–0.
4. Johnson, C.M., et al., Meta-analyses of colorectal cancer risk factors. Cancer causes & control, 2013. 24: p. 1207–1222.
5. Harfouch, R., et al., Epidemiology and risk factors of colorectal cancer in Syria: a single- center retrospective study. Eur Rev Med Pharmacol Sci, 2022. 26(13): p. 4654–4658.
6. Lewandowska, A., et al., Risk factors for the diagnosis of colorectal cancer. Cancer control, 2022. 29: p. 10732748211056692.
7. Sninsky, J.A., et al., Risk factors for colorectal polyps and cancer. Gastrointestinal endoscopy clinics of North America, 2022. 32(2): p. 195–213.
8. McCashland, T.M., et al., Gender differences in colorectal polyps and tumors. Official journal of the American College of Gastroenterology| ACG, 2001. 96(3): p. 882–886.
9. Roshandel, G., F. Ghasemi-Kebria, and R. Malekzadeh, Colorectal cancer: epidemiology, risk factors, and prevention. Cancers, 2024. 16(8): p. 1530.
10. Macrae, F.A., et al., Epidemiology and risk factors for colorectal cancer. Wolters Kluwer.(Accessed on December 12, 2024.), 2025.
11. Bazensky, I., C. Shoobridge-Moran, and L.H. Yoder, Colorectal cancer: an overview of the epidemiology, risk factors, symptoms, and screening guidelines. Medsurg Nursing, 2007. 16(1): p. 46.
12. Li, Q., et al., Smoking as a risk factor for colorectal neoplasms in young individuals? A systematic meta-analysis. International Journal of Colorectal Disease, 2023. 38(1): p. 114.
13. Bidgoli, N., et al., Risk of colorectal cancer in Parkinson’s disease: a systematic review and meta-analysis of 11 million participants. BMC neurology, 2025. 25(1): p. 1–10.
14. Chang, V.C., et al., Risk factors for early-onset colorectal cancer: a population-based
case–control study in Ontario, Canada. Cancer causes & control, 2021. 32: p. 1063–1083.
15. Hampel, H. and P. Peltomaki, Hereditary colorectal cancer: risk assessment and management. Clinical genetics, 2000. 58(2): p. 89–97.
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