Cancer Research UK : Bowel Cancer risk factors

Bowel Cancer risk factors

This section contains information on bowel cancer and diet, focusing on meat and fish,fibre, fruit and vegetable consumption, fat, folate, calcium and selenium. It also details the evidence on bowel cancer risk and obesity, physical exercise, alcohol and tobacco, NSAIDS, Statins, HRT and oral contraceptives, other medical conditions, family history and screening.

Diet and bowel cancer risk

Bowel cancer incidence is generally higher in populations with ‘westernised’ diets and these populations also tend to have a higher proportion of overweight and obese people and lower levels of exercise.

Meat and fish

The EPIC study (European Prospective Investigation into Cancer and Nutrition), based on about 1,300 bowel cancer cases, has shown a significant 55% increase in risk for a 100g/day increase in consumption of red and processed meat1. Red meat is defined as all fresh, minced and frozen beef, veal, pork and lamb. Processed meat is any meat preserved by methods other than freezing, including marinating, smoking, salting, air drying or heating and includes ham, bacon, sausages, pate and tinned meat.

This is supported by results of three meta-analyses, which show a 20-30% increased risk of bowel cancer in relation to 100-120g/day of red meat and a 9-50% increased risk of bowel cancer in relation to 25-30g/day of processed meat. 2-4

The EPIC study also supports a significant risk reduction of approximately 30% with higher intake of fish, including fresh, canned, salted and smoked.1

Fibre

The EPIC study has shown a lower risk of colorectal cancer with higher fibre intake, after adjustment for a number of potential confounding factors, including folate (see below).5

There was about a 20-30% reduction in risk of colon cancer in men and women in the highest quintile of fibre consumption, compared to the lowest quintile. The association was strongest for left-sided colon cancer, with a greater than 40% risk reduction for the highest quintile of fibre intake, but no significant risk reduction was shown for rectal cancer.

A new meta-analysis, excluding the results of the EPIC study, showed no significant reduction in risk of colorectal cancer with high consumption of fibre, but very low fibre intake (less than 10 g/day) did significantly increase bowel cancer risk.6

In some studies null findings may be due to an insufficient range of fibre intake or other methodological problems. Alternatively, other features of a high fibre diet (a plant-based diet rich in fruits, vegetables, and whole grains) could be responsible for the protective effect. Despite this lack of consensus, investigators agree that fibre should be eaten as part of a healthy diet because of its potential in preventing colorectal cancer and its beneficial effects on other chronic diseases, such as heart disease and diabetes.

Fruit and vegetables

A meta-analysis showed a reduction in risk of distal colon cancer in relation to intake of fruit and vegetables separately and combined.7 However, a comprehensive review by the International Agency for Research on Cancer (IARC) concluded that the inverse association was so modest that confounding could not be ruled out as an explanation for the observed association.8

Fat

There is probably no positive association between high fat intake and bowel cancer risk, independent of meat intake.9

A Swedish cohort study showed women consuming the highest amounts of full-fat dairy products had a significantly lower risk of bowel cancer,10 and a randomised trial found a low fat dietary intervention offered no significant protection against bowel cancer.11

Folate, calcium, vitamin B and vitamin D

There is evidence that a diet high in folate (a water-soluble B vitamin which occurs naturally in foods especially fruit and vegetables) protects against bowel cancer12 while folic acid (the synthetic form of folate) supplements are not linked to a lower risk 12,13.

Recently a large nested case-control study reported a significant increase in risk of bowel cancer in people with higher circulating levels of folate.14 More studies are needed to clarify the role of circulating levels of folate and supplements.

Higher dietary and body levels of vitamin B6 have been shown to reduce risk of colorectal cancer.12, 15,16 There is some evidence that having higher levels of vitamin B12 reduces risk of rectal cancer.61

Higher calcium intake from diet and supplements has been shown in several prospective studies to protect against bowel cancer.17 Vitamin D intake modifies this association, with the risk reduction limited to individuals with relatively high intakes of both nutrients.18 One randomised trial has showed no reduction in bowel cancer risk for individuals randomised to vitamin D and calcium supplementation.19

At least eight studies have assessed risk of bowel cancer in relation to serum levels of the vitamin D metabolite, 25(OH)D,19-26 all but one20 showing a significant risk reduction in people with highest body levels, or a significant trend with increasing levels. While diet makes a contribution to vitamin D levels, other factors such as skin colour and sun exposure have a greater effect.

Diet summary

Overall, the recommendations of the Working Group on Diet and Cancer of the Committee on Medical Aspects of Food and Nutrition Policy (COMA) published in 1998 still hold true: “There is moderately consistent evidence that diets with less red and processed meat and more vegetables and fibre are associated with reduced risk of colorectal cancer”.27 Increasing intake of fish and milk can probably be added to this.

In many countries, diet changed substantially in the second half of the twentieth century, with an increase in the consumption of meat, dairy products, vegetable oils, fruit juice and alcoholic beverages, and a decrease in the consumption of starchy staple foods such as bread, potatoes, rice and maize flour.28

In recent years in Britain there has been a fall in the consumption of red meat accompanied by an increase in consumption of fresh fruit and a steady consumption of fresh vegetables (excluding potatoes) as Figure 5.1 shows.29

Figure 5.1: Household food consumption, Great Britain, 1974 - 2000

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However, around three quarters of the population is still falling short of the recommended five portions of fruit and vegetables a day (Figure 5.2).29

Figure 5.2: The number of portions of fruit and vegetables eaten per day by adults aged 16 and over, England, 2004

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Obesity and bowel cancer risk

Obesity is associated with an increased risk of colon cancer. The risk of colon cancer increases by an estimated 25% in overweight and 50% in obese men.30 The association between overweight and bowel cancer risk is weaker in women, with the most recent meta-analysis reporting a 9% risk increase for a five-point increase in body mass index (BMI).31 Oestrogen may modify the association between body mass index (BMI) and risk in women.32

The prevalence of obesity has increased in British adults as shown in Figure 5.3.33

Figure 5.3: Trends in bodyweight by sex, England, 1995 and 2004

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Between 1995 and 2004 the percentage of obese men in England rose from 15 to 24% and for women from 18 to 24%.29 At least 10% of colon cancers in the UK are related to overweight or obesity.62

Physical exercise and bowel cancer risk

Individuals, particularly men, with high levels of physical activity throughout their lives are at lower risk for colon cancer but it is uncertain whether physical activity modifies rectal cancer risk.34-36

Alcohol and tobacco and bowel cancer risk

Alcohol intake increases colorectal cancer risk, with a pooled analysis of eight cohort studies reporting a borderline statistically significant 16% risk increase for people drinking 30–45 g/day of alcohol and a significant 41% risk increase for people drinking 45 g/day or more.37

Two studies excluded from this analysis show a risk increase at lower levels of alcohol intake, a Japanese cohort study showing a significant 40% risk increase for men consuming 20 g/day or more38, and an American cohort study a significant 150% risk increase in people consuming one or more drinks of spirits a day.39

Alcohol may have a particularly strong effect in people with low folate levels in their diet.40

There is a strong association between tobacco smoking and increased risk for adenomas,41, 42 but the evidence is less certain for colorectal cancer43 and a review conducted by IARC was unable to conclude that smoking was causally linked to colorectal cancer.44

Nonsteroidal anti-inflammatory drugs (NSAIDs) and bowel cancer risk

People reporting long-term (at least ten years) regular use of aspirin (at least two tablets a day) have a 50% reduced risk of bowel cancer and there is a similar risk reduction with non-aspirin NSAIDs.45

The mechanisms of NSAIDs in the prevention of colorectal cancer are not fully understood, but it is thought they suppress the enzyme COX-2, inhibiting polyp growth.46 Two randomised trials confirmed that aspirin reduces risk of colorectal adenomas. 47, 48 However, because of the known side-effects of regular aspirin consumption (gastro-intestinal haemorrhage) both trials concluded it was premature to recommend widespread use of aspirin as a chemopreventive agent.

Hormone replacement therapy (HRT) and oral contraceptives(OCs) and bowel cancer risk

A meta-analysis reported that ever use of HRT is associated with a 20% reduction in risk of colon and rectum cancers and current use with a 34% reduction in the risk of all bowel cancer.49

Since that study, a large nested case-control study reported significant risk reductions for women taking oestrogen-only HRT, with the greatest risk reduction for women taking the HRT trans-dermally.50

Results from randomised trials have partly confirmed the observational results. A 44% reduced risk in colorectal cancer risk was seen after five years of oestrogen and progestin use in one trial,51 but no reduction in risk was found for use of oestrogen-only HRT,52 while another found a non-significant reduced risk of colon cancer in women with pre-existing cardiovascular disease randomised to combined HRT.53

Ever use of OCs is associated with an 18% reduced risk of colorectal cancer, according to the results of a meta-analysis.54 A large case-control study published since this meta-analysis reported a non-significant 11% risk reduction for women that had ever used OCs, while there was a significant risk reduction of almost 50% for rectal cancer for use of OCs within the previous 14 months.55

Other medical conditions and bowel cancer risk

There is some recent evidence that people who have had their gallbladder removed may have a modest increase in bowel cancer risk.56,63-64 However, not all studies have shown an association.65

A large meta-analysis reported a significant 30% increased risk of colorectal cancer in type II diabetes patients.57 Ulcerative colitis and Crohn’s disease also carry a raised risk for colorectal cancer.58

Family history and bowel cancer risk

A minority of bowel cancers are linked to a dominantly inherited predisposition.(see molecular biology and genetics page). However, people who have a first-degree relative with the disease are at approximately twice the average risk, higher if the relative with the disease is young or if there is more than one first-degree relative affected.59

Screening and bowel cancer risk

Randomised trials show that people attending at least one round of screening with the fecal occult blood test have a 25% reduction in risk of death from bowel cancer. 60

References

Norat, T., et al., Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition. J Natl Cancer Inst, 2005. 97(12): p. 906-16.
Larsson, S.C. and Wolk, A. Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. IJC, 2006. 119(11): p. 2657-64.
Norat, T., et al., Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies. Int J Cancer, 2002. 98(2): p. 241-56.
Sandhu, M.S., I.R. White, and K. McPherson, Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach. Cancer Epidemiol Biomarkers Prev, 2001. 10(5): p. 439-46.
Bingham, S.A., et al., Is the association with fiber from foods in colorectal cancer confounded by folate intake? Cancer Epidemiol Biomarkers Prev, 2005. 14(6): p. 1552-6.
Park, Y., et al., Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies. Jama, 2005. 294(22): p. 2849-57
Koushik, A. et al. Fruits, vegetables and colon cancer risk in a pooled analysis of 14 cohort studies. JNCI, 1996. 99(19): p. 1471-83.
IARC, Handbooks of Cancer Prevention: Fruit and vegetables. ed., ed. Vol. 2003, Lyon: IARC Press.
Giovannucci, E., et al., Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res, 1994. 54(9): p. 2390-7.
Larsson, S.C., L. Bergkvist, and A. Wolk, High-fat dairy food and conjugated linoleic acid intakes in relation to colorectal cancer incidence in the Swedish Mammography Cohort.Am J Clin Nutr, 2005. 82(4): p. 894-900.
Beresford, S.A., et al., Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. Jama, 2006. 295(6): p. 643-54.
Sanjoaquin, M.A., et al., .Folate intake and colorectal cancer risk: A meta-analytical approach. Int J Cancer, 2005. 113(5): p. 825-8
Zhang, S.M., et al., Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women. Am J Epidemiol, 2006. 163(2): p. 108-15.
Van Guelpen, B., et al., Low folate levels may protect against colorectal cancer. Gut, 2006. p.
Wei, E.K., et al., Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women. J Natl Cancer Inst, 2005. 97(9): p. 684-92.
Larsson, S.C., E. Giovannucci, and A. Wolk, Vitamin B6 intake, alcohol consumption, and colorectal cancer: a longitudinal population-based cohort of women. Gastroenterology, 2005. 128(7): p. 1830-7.
Cho, E., et al., Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies. J Natl Cancer Inst, 2004. 96(13): p. 1015-22.
Wactawski-Wende, J., et al., Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med, 2006. 354(7): p. 684-96.
Braun, M.M., et al., Colon cancer and serum vitamin D metabolite levels 10-17 years prior to diagnosis. Am J Epidemiol, 1995. 142(6): p. 608-11.
Levine, A.J., et al., .Serum 25-hydroxyvitamin D, dietary calcium intake, and distal colorectal adenoma risk. Nutr Cancer, 2001. 39(1): p. 35-41
Peters, U., et al., Vitamin D, calcium, and vitamin D receptor polymorphism in colorectal adenomas. Cancer Epidemiol Biomarkers Prev, 2001. 10(12): p. 1267-74.
Peters, U., et al., Circulating vitamin D metabolites, polymorphism in vitamin D receptor, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev, 2004. 13(4): p. 546-52.
Tangrea, J., et al., Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men. Cancer Causes Control, 1997. 8(4): p. 615-25.
Feskanich, D., et al., Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev, 2004. 13(9): p. 1502-8.
Garland, C.F., et al., Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet, 1989. 2(8673): p. 1176-8.
Jacobs, E.T., et al., Selenium and Colorectal Adenoma: Results of a Pooled Analysis. J Natl Cancer Inst, 2004. 96(22): p. 1669-1675.
Committee on Medical Aspects of Food and Nutrition Policy, Nutritional Aspects of the Development of Cancer. 1998, Department of Health: London.
Department of Environment Food and Rural Affairs, National Food Survey 2002.
National Statistics, Health Survey for England 2004.
Moghaddam, A.A. et al. Obesity and risk of colorectal cancer: A meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev, 2007. 16(12): p. 2533-47.
Renehan, A.G. et al., Body mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Am J Epidemiol, 2000. 152(9): p. 847-854.
Slattery, M.L., et al., Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States). Cancer Causes Control, 2003. 14(1): p. 75-84.
DH. Health Survey for England: Trend data 1993-2002. [Summary of key findings] 2003
Wei, E.K., et al., Comparison of risk factors for colon and rectal cancer. Int J Cancer, 2004. 108(3): p. 433-42.
Slattery, M.L., et al., Physical Activity and Colorectal Cancer. Am. J. Epidemiol., 2003. 158(3): p. 214-224.
IARC, IARC Handbooks of Cancer Prevention: Weight Control and Physical Activity. ed. H. Vaino and F. Bianchini. Vol. 6. 2002, Lyon: IARC Press.
Cho, E., et al., Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies. Ann Intern Med, 2004. 140(8): p. 603-13.
Otani, T., et al., Alcohol consumption, smoking, and subsequent risk of colorectal cancer in middle-aged and elderly Japanese men and women: Japan Public Health Center-based prospective study. Cancer Epidemiol Biomarkers Prev, 2003. 12(12): p. 1492-500.
Su, L.J. and L. Arab, Alcohol consumption and risk of colon cancer: evidence from the national health and nutrition examination survey I epidemiologic follow-up study. Nutr Cancer, 2004. 50(2): p. 111-9.
Giovannucci, E., et al., Alcohol, low-methionine--low-folate diets, and risk of colon cancer J Natl Cancer Inst, 1995. 87(4): p. 265-73.
Botteri, E., et al., Cigarette smoking and adenomatous polyps: a meta-analysis. Gastroenterology, 2008. 134(2): p. 388-95.
Larsen, I.K., et al., Lifestyle as a predictor for colonic neoplasia in asymptomatic individuals. BMC Gastroenterol, 2006. 6: p. 5.
Gandini, S., et al. Tobacco smoking and cancer: a meta-analysis. IJC, 2008. 122 (1): p. 155-64.
IARC, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Tobacco smoke and involuntary smoking. Volume 83 ed. 2004, Lyon: IARC Press.
Chan, A.T., et al., Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. Jama, 2005. 294(8): p. 914-23.
Ricchi, P., et al., Minireview: Nonsteroidal anti-inflammatory drugs in colorectal cancer: from prevention to therapy. Br J Cancer, 2003. 88(6): p. 803-7.
Baron, J.A., et al., A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med, 2003. 348(10): p. 891-9.
Sandler, R.S., et al., A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med, 2003. 348(10): p. 883-90.
Grodstein, F., P. Newcomb, and M. Stampfer, Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am J Med, 1999. 106: p. 574-582.
Csizmadi, I., et al., The effects of transdermal and oral oestrogen replacement therapy on colorectal cancer risk in postmenopausal women. Br J Cancer, 2004. 90(1): p. 76-81.
Chlebowski, R.T., et al., Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med, 2004. 350(10): p. 991-1004.
Anderson, G.L., et al., Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. Jama, 2004. 291(14): p. 1701-12.
Hulley, S., C. Furberg, and E. Barrett-Connor, Noncardiovascular disease outcomes duri ng 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA, 2002. 288(1): p. 58-66.
Fernandez, E., et al., Oral contraceptives and colorectal cancer risk: a meta-analysis. Br J Cancer, 2001. 84(5): p. 722-7.
Nichols, H.B., et al., Oral contraceptive use, reproductive factors, and colorectal cancer risk: findings from Wisconsin. Cancer Epidemiol Biomarkers Prev, 2005. 14(5): p. 1212-8.
Shao, T. and Y.X. Yang, Cholecystectomy and the risk of colorectal cancer. Am J Gastroenterol, 2005. 100(8): p. 1813-20.
Larsson, S.C., N. Orsini, and A. Wolk, Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst, 2005. 97(22): p. 1679-87.
Potter, J.D. and Hunter, D. Colorectal Cancer. In: Adami, H.O., Hunter, D. and Trichopoulos, D., eds. Textbook of cancer epidemiology. New York: OUP; 2002:188-211.
Johns, L. and Houlston, R. A systematic review and meta-analysis of familial colorectal cancer risk. Am Journal of Gastroenterol, 2001. 96(10): p. 2992-3003.
Hewitson, P. et al. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Review, 2007. 1: CD001216.
Dahlin, A.M. et al. Plamsa vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study. IJC, 2008. 122(9): p. 2057-61.
Bergstrom, A. et al. Overweight as an avoidable cause of cancer in Europe. Int J Cancer, 2007. 91: p. 421-30.
Schernhammer, E.S. et al., Cholecystectomy and the risk for developing colorectal cancer and distal colorectal adenomas. Br J Cancer, 2003. 88(1): p. 79-83.
Lagergren, J. et al. Intestinal cancer after cholecystectomy: is bile involved in carcinogenesis?. Gastroenterology, 2001. 121(3): p. 542-7.
Goldacre, M.J. et al. Cancer after cholecystectomy: record-linkage cohort study. Br J Cancer, 2007. 92(7): p. 1307-9.

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