Alcohol Consumption Strongly Linked to Risk of Colorectal Cancer: A dose-dependent association
James Meschino DC, MS, ROHP
Colorectal cancer is the second most common cancer in females and the third most common cancer in males worldwide. Both genetic and environmental risk factors have been shown to contribute to the development of colorectal cancer. Some of the environmental risk factors for colorectal cancer appear to include low-fibre diet,obesity,a sedentary lifestyle, and smoking. (1) Some additional evidence suggests that suboptimal intake of calcium and vitamin D may also contribute to the risk of colorectal cancer. (2) Evidence also suggests that most colorectal cancers develop from colorectal adenomas and present morphological and genetic progression via an adenoma–carcinoma sequence. Cigarette smoking,red and processed meat intake, obesity and physical inactivity, have been suggested to be risk factors for colorectal adenoma. (1)
Alcohol intake is one of the primary risk factors for many human cancers, and is strongly associated with cancers of oral cavity, pharynx, larynx, oesophagus, liver, breast, and notably the colon and rectum. A systematic review with meta-analysis, published in 2014, provided an update regarding the association between alcohol consumption and risk of colorectal cancer. The meta-analysis included twenty-three case–control studies and two cohort studies. The results showed that “all drinkers were associated with 17% increased risk for colorectal cancer, compared with non-drinkers or occasional alcohol drinkers. The dose–response analysis demonstrated that for drinkers of 10, 25, 50 and 100 g/day alcohol consumption, the estimated relative risks of colorectal adenoma were 1.02 (95% CI 0.89–1.16), 1.06 (95% CI 0.92–1.20), 1.16 (95% CI 1.02–1.33) and 1.61 (95% CI 1.42–1.84) respectively, in comparison with non-/occasional drinkers. The risks were consistent in the subgroup analyses of gender and site of adenoma, while it was stronger in European studies than the studies in the US and Asia”. (1)
Mechanism of Alcohol Damage in Colorectal Cancer
Alcohol consumption may increase risk of colorectal cancer via a number of documented mechanisms. Alcohol intake may lead to folic acid deficiency in the colon and rectum, via folate malabsorption. Folate is required for the synthesis of certain DNA bases and to methylate DNA structure. Marginal deficiencies of folate are known to increase the risk ofDNA hypomethylation, DNA mutations and strand breaks, which are shown to increase cancer risk, including colorectal cancer. (3-10) As well, intestinal bacteria, which have high activity of the alcohol dehydrogenase enzyme, could oxidise ethanol in the colon and rectum and generate a considerable level of acetaldehyde, which is known to initiate and promote cancer via several mechanisms. (1,11) In addition, alcohol may inhibit DNA repair enzymes, suppress immune surveillance to tumour, alter the composition of bile acids and induce the expression of liver cytochrome P-450 enzymes, all of which may contribute to adenoma development. (1)
The study researchers noted that this was the first study to conduct a meta-analysis concerning colorectal adenoma risk and alcohol intake, with an extensive search of literature to identify the published research up to January 2014. The majority of the studies evaluated included multiple confounders, containing age, dietary factors, drug use, physical activity and others. And the risks of categories stratified by gender, geographical region and site of adenomas were estimated separately. Traditional meta-analysis by categories of alcohol consumption and dose–response analysis were used to investigate the association. As such, the results of the study linking alcohol to risk of colorectal cancer appear to be consistent and reliable. (1)
The researchers go on to suggest that screening guidelines for colorectal cancer should possibly be adjusted for individuals who have lifestyle and environmental risk factors that place them in a higher risk category, such as smoking, obesity, (or higher body mass index), lack of exercise, frequent alcohol consumption, etc. Early screening for colorectal cancer (colonoscopy) is proven to be a valuable tool to detect early stage cancerous and precancerous lesions, and as a therapeutic intervention, allows physicians to remove suspicious polyps, preventing their progression to malignant lesions. “The earlier screening of this new subset of ‘high-risk individuals’ may contribute to earlier detection, and subsequently, reduction of morbidity and mortality from colorectal cancer.” (1)Finally, Cancer Research UK provides an excellent overview (with scientific references) of the known risk factors for colorectal cancer, including a comprehensive section on specific dietary and lifestyle risk factors linked to this condition. It is an excellent review for primary health care practitioners in my view. (12) Based on the 2014 research update reviewed in this article,primary health care practitioners should consider performing a basic dietary, lifestyle, anthropometric screening on all new patients to help identify those with important risk factors for colorectal cancer. In those falling into a higher risk category, a short note should be sent to the patient’s family doctor explaining the findings with a recommendation that the patient undergo a colonoscopy, if they have not had one within the preceding 3-5 years.
In-office Screening Questions
Here is a sample of a quick series of screening questions to identify those who many benefit from a colonoscopy, regardless of their age.
|1.||Regarding fiber intake from whole grains, vegetables, peas, beans, fiber supplements (e.g. psyllium, flaxseed, wheat germ, chia seeds) and high fiber fruits such as apples, peaches, pears, and plum, how would you rate your daily fiber intake?|
|A.||High fiber intake (aiming for 30 gm of fiber per day or more)|
|B.||Moderate fiber intake (I strive to include some higher fiber foods on most days)|
|C.||Low fiber intake (I don’t eat a meaningful quantity of any combination of these foods daily)|
|2.||How much endurance exercise or physical activity to get each week, on average (e.g. fast walking, jogging, cycling, any aerobic exercise)|
|A.||More than 150 min/week|
|B.||60 – 140 min/week|
|C.||Less than 60 min/week|
|3.||What is your weight in lbs? lbs.|
|4.||What is your height in feet and inches? feet inches|
|Calculate Body Mass Index by dividing weight by weight squared (height is in meters squared and weight is in kilograms) Here is an online tool to make the calculation quick and easy: http://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm|
|Is the Body Mass Index (BMI) 30 or above? rYes rNo|
|Is the Body Mass Index (BMI) between 25 and 29.9? rYes rNo|
|Is the Body Mass Index (BMI) between 20 and 24.9 (ideal)? rYes rNo|
|5.||Are you a smoker? rYes rNo|
|If “YES”, how many cigarettes per day? # per day|
|6.||Are you an ex-smoker? rYes rNo|
|If “YES”, how many cigarettes per day? # years|
|7.||How much alcohol do you consume per day, on average? Note that one drink equals:
· 12 oz beer
· 5 oz glass of wine
· 1.5 oz hard liquor
|A.||Non-drinker or drink small amounts very infrequently|
|B.||1 drink per day|
|C.||2-3 drinks per day|
|D.||More than 3 drinks per day|
|8.||Do you know your blood level of vitamin D? rYes rNo|
|If “YES”, is it above 75nmol/L (30ng/ml)? rYes rNo|
|If “YES”, is it below 75nmol/L (30ng/ml)? rYes rNo|
|9.||Do you ingest a minimum of 500 mg of calcium each day from the dietary supplements you take?
|10.||Has your biological mother, father, or a biological brother or sister developed or died from colon or rectal cancer?
- -Z. Zhu, Y.-M. Wang, Q.-Y. Zhou, K.-F. Zhu, C.-H. Yu, Y.-M. Li. Alcohol consumption and risk of colorectal adenoma. Aliment Pharmacol Ther. 2014;40(4):325-337. (http://www.medscape.com/viewarticle/829964_print)
- http://www.ncbi.nlm.nih.gov/pubmed/24623471 (International Journal of Cancer. 2014 – Calcium intake and colorectal cancer risk: dose-response meta-analysis of prospective observational studies)
- Blount, B.C., M.M. Mack, C. Wehr, J. MacGregor, R. Hiatt, G. Wang, S.N. Wickramasinghe, R.B. Everson and B.N. Ames, Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage., Proc. Natl. Acad. Sci. USA 94 (1997) 3290-3295.
- Fenech, M., C. Aitken and J. Rinaldi, Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults, Carcinogenesis 19 (1998) 1163-1171.
- Giovannucci, E., M.J. Stampfer, G.A. Colditz, E.B. Rimm, D. Trichopoulos, B.A. Rosner, F.E. Speizer and W.C. Willett, Folate, methionine, and alcohol intake and risk of colorectal adenoma, J. Natl. Cancer Inst. 85 (1993) 875-884.
- Mason, J.B., Folate and colonic carcinogenesis: Searching for a mechanistic understanding, J. Nutr. Biochem. 5 (1994) 170-175.
- Giovannucci, E., Stampfer, M. J., Colditz, G. A., Hunger, D. J., Fuchs, C., Rosner, B. A., Speizer, F. E., Willett, W. C., Multivitamin use, folate, and colon cancer in women in the nurses’ health study, Ann. Intern. Med. 129 (1998) 517-524.
- Wallock, L., A. Woodall, R. Jacob and B. Ames, Nutritional status and positive relation of plasma folate to fertility indices in nonsmoking men [abstract], FASEB J. 11 (1997) A184 -1068.
- Boushey, C.J., S.A. Beresford, G.S. Omenn and A.G. Motulsky, A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes, J. Am. Med. Assoc. 274 (1995) 1049-1057.
- Subar, A.F., G. Block and L.D. James, Folate intake and food sources in the US population, Am. J. Clin. Nutr. 50 (1989) 508-516.