Colorectal Cancer And Risky Lifestyle Habits
Overview
Colorectal cancer (CRC) is a common form of cancer worldwide, yet the relationship between nutrient intake and CRC risk remains unclear. This study aimed to explore the potential connections between dietary intake, supplements, and the risk of developing CRC through an extensive literature review.
An exhaustive online search was conducted across databases including PubMed, Scopus, Web of Science, and the Cochrane Library, covering studies from January 1990 to March 2023. The search focused on clinical trials and cohort studies to assess the association between various dietary components or supplements and CRC risk.
The findings suggest that long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may lower the risk of CRC, with eight studies supporting this protective effect and four studies finding no significant association. Additionally, certain dietary components such as probiotics, prebiotics, and synbiotics may contribute to CRC prevention, though the evidence is mixed, with three studies indicating positive effects and three finding no association. The evidence regarding the protective effects of micronutrient supplementation, including vitamin D, folate, zinc, and selenium, remains inconclusive, with some studies showing benefits and others reporting no association.
While certain dietary supplements, such as n-3 LCPUFAs and probiotics, show promise in reducing colorectal cancer risk, further research is needed to confirm these findings and clarify the mechanisms involved.
Introduction
Colorectal cancer (CRC) is a widespread malignancy and a leading cause of cancer-related mortality. In recent years, Iran has seen a rise in CRC prevalence, with an incidence rate of 7–8 cases per 100,000 individuals. Several factors contribute to the increased risk of colorectal cancer, including genetics, age, and lifestyle choices. Other risk factors include hereditary disorders, alcohol consumption, smoking, lack of physical activity, a diet high in fats, and the intake of processed red meats. The role of dietary components and supplements in influencing CRC risk has been studied extensively, though findings have been inconsistent. Poor nutrition is widely recognized as a key factor in CRC-related mortality, suggesting that dietary changes could potentially mitigate cancer severity.
Numerous studies have explored the relationship between dietary patterns and colorectal cancer risk. Epidemiological research has highlighted the possible protective effects of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), against colorectal cancer. However, the evidence remains inconclusive. While one meta-analysis suggested that fish oil could reduce colorectal cancer risk by 12%, other studies have indicated potential risks, such as a study by Daniel et al. that linked higher intake of α-linolenic acid (ALA) with an increased risk of colorectal cancer in women.
Additionally, some research has identified other dietary components like folate, trace elements, and probiotics as potentially protective against CRC. For example, an animal study by Shang et al. demonstrated that probiotics could inhibit the proliferation of colon tumor cells. Another study suggested that probiotic supplementation might reduce serum zonulin levels, which could affect intestinal permeability and lead to inflammation and cancer in patients with colorectal metastases. Despite these findings, the evidence regarding the impact of dietary components on CRC remains limited.
Given the inconclusive nature of existing research, this study seeks to further investigate the potential effects of nutritional supplements on both the risk of developing CRC and its progression.
Method
This systematic review was conducted following the PRISMA guidelines to explore the potential preventative effects of dietary supplements on colorectal cancer (CRC). The review focused on intervention and cohort studies involving adult participants to assess the impact of various dietary components and supplements on colorectal cancer risk. The search and screening process, depicted in Figure 1, adhered to predefined criteria to ensure the inclusion of relevant studies.
The search strategy involved a comprehensive literature search across several databases, including the Cochrane Library, PubMed, Scopus, and Web of Science. The search terms included a combination of MeSH and non-MeSH terms related to diet, nutrients, specific dietary supplements, and colorectal cancer. Examples of search terms used are “Diet,” “Dietary,” “Fish oil,” “EPA,” “DHA,” “vitamin D,” and “colorectal cancer.” Additionally, a manual review of reference lists from eligible studies and related reviews was performed to capture all relevant literature.
Data extraction was performed independently by two researchers, with oversight from a chief investigator to resolve any disagreements. The extracted data included details such as the first author’s name, publication year, participant health status, type and dosage of dietary supplements, and main outcomes. The full texts of articles deemed potentially eligible were thoroughly reviewed before final inclusion in the analysis.
Inclusion Criteria
Eligibility criteria for the review included English-language interventional and cohort studies published after 1990 that investigated the relationship between dietary supplements and colorectal cancer or colorectal neoplasia.
Exclusion Criteria
Studies were excluded if they had a follow-up duration of less than one week, were conducted before 1990, or did not report relevant outcomes.
Result
In the initial phase of the study, 219 articles were gathered. After excluding non-English articles (7), non-clinical-trial or cohort studies (146), and unrelated studies (45), a total of 21 studies were included in the systematic review.
The review examined 12 studies focused on the effects of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) on colorectal cancer (CRC). Out of these, 8 studies demonstrated beneficial effects, while 4 did not observe any benefit. LCPUFAs, particularly EPA and DHA derived from fish oil, are recognized for their anti-inflammatory properties. However, findings on their effects on CRC remain inconsistent. Some research suggests a protective relationship between n-3 PUFAs intake and CRC, with fish oil reducing CRC risk by 12% in one meta-analysis. A Swedish cohort study, following participants for 21.3 years, found no overall link between n-3 LCPUFAs and CRC risk, although a high intake of DHA was associated with a reduced risk of rectal cancer. Additionally, an elevated n-6 PUFA/n-3 LCPUFA ratio has been linked to an increased colorectal cancer risk. Some studies found a protective effect from cod liver oil supplementation, while others noted that ALA increased CRC risk in women but had no impact on men. A meta-analysis and various clinical trials did not find significant associations between n-3 fatty acid supplementation and CRC risk.
Six studies investigated the effects of probiotics, prebiotics, and synbiotics on colorectal cancer, with mixed results: three studies reported a positive effect, while the other three found no association. Probiotics are beneficial microorganisms that enhance gut flora, while prebiotics promote the growth of these probiotics. Synbiotics combine both probiotics and prebiotics. Although animal studies have shown that probiotics can inhibit colon tumor cell proliferation, human studies have yielded variable results. One randomized controlled trial found no overall association between prebiotic fiber intake and CRC risk, but an increased risk of CRC mortality was noted with insoluble fiber supplements. Probiotics have shown promise in reducing postoperative complications and improving immune function in CRC patients, yet the variability in findings calls for further research.
Two clinical trials explored the impact of vitamin D on CRC. One study reported a positive effect, while the other did not find any association. Vitamin D, synthesized internally through UV exposure, plays a role in regulating cell proliferation and apoptosis, potentially offering anticancer benefits. Higher vitamin D levels have been linked to a reduced incidence of CRC in cohort studies and meta-analyses. Calcium intake has also been associated with a decreased risk of adenomatous polyps, although some studies found no significant link between calcium or vitamin D supplementation and colorectal cancer risk.
Folate, or vitamin B₉, may have a dual role in colorectal cancer development. Increased dietary folate is protective against CRC before the onset of neoplastic lesions, but after initial lesions, folate consumption might promote tumorigenesis. Studies have shown that folate deficiency increases colorectal cancer risk, though folate’s protective effect may only apply to those deficient in it. Some research suggests that folate from food, rather than supplements, is beneficial in reducing colorectal cancer risk. Folate may reduce CRC risk by altering DNA methylation patterns and DNA synthesis, thereby affecting tumorigenesis.
The review also touched on trace elements and their impact on CRC. Zinc deficiency was found to potentially increase colorectal cancer risk, while zinc supplementation was associated with improved quality of life and reduced fatigue in colorectal cancer patients. Selenium supplementation has shown potential in lowering colorectal cancer risk, with studies indicating that selenium may reduce oxidative stress, regulate immune response, and aid in DNA repair.
Conclusion
Dietary intake plays a significant role in the development of colorectal cancer (CRC), with dietary modifications potentially reducing CRC risk by up to 50%. Despite this, research on the impact of dietary supplements on CRC risk has been inconclusive. Omega-3 fatty acids, particularly n-3 polyunsaturated fatty acids (PUFAs), are suggested to reduce CRC risk, though some studies have not confirmed this association. The anticancer effects of n-3 PUFAs may be linked to their ability to inhibit arachidonic acid-derived eicosanoids, which are involved in inflammation and cancer development.
Research, including a cohort study by Liu et al., has highlighted the health benefits of omega-3 PUFAs, such as the prevention of inflammatory diseases and potential anticancer properties. Several studies indicate an inverse relationship between omega-3 intake and various cancers, including CRC. Additionally, a large prospective analysis found that consuming total fish, including fatty and lean fish, is associated with reduced CRC risk. Omega-3 PUFAs have been reported to lower inflammatory markers like TNF-α and IL-6, and improve outcomes for CRC patients undergoing adjuvant therapies.
Other dietary components, such as probiotics, prebiotics, and synbiotics, may also help in CRC prevention. Probiotic supplementation has been shown to enhance gut microbiota diversity, improve quality of life for CRC patients, reduce postoperative infections, and inhibit inflammatory cytokine production. Probiotics may also positively affect intestinal permeability and reduce aberrant crypt foci while boosting immune responses.
Additionally, diets rich in vitamin D, folic acid, zinc, and selenium have been associated with CRC prevention. Vitamin D3 combined with omega-3 fatty acids may improve inflammation and nutritional status in CRC patients. Vitamin D’s active metabolite, calcitriol, influences cancer cell proliferation and apoptosis. Zinc and selenium, through their antioxidant properties, may also help mitigate CRC progression.
In summary, dietary factors significantly impact CRC risk and represent a potential strategy for nutritional prevention. However, results across studies have been inconsistent, partly due to variations in study design, sample sizes, and supplement formulations. Further longitudinal research is needed to confirm these findings and elucidate the mechanisms by which diet affects CRC risk. Understanding these interactions could lead to novel approaches for CRC prevention and management.
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