Various lifestyle factors and drugs have been associated with reduced risk of colorectal cancer, and some with increased risk. In this section the evidence and recommendations on cancer prevention are subdivided into diet, physical activity, smoking, alcohol, hormone therapy and chemoprevention. There is also a section on screening for colorectal cancer.

2.1 Diet and excess weight

Diet has long been regarded as the most important environmental influence on colorectal cancer, and this is reflected in the volume of studies testing the dietary hypothesis. However, there are two major problems in the interpretation of the observational studies, firstly, that diet is related to other aspects of lifestyle that may influence risk and, secondly, that people eat food rather than nutrients. In consequence, it is difficult to identify the specific components of diet that influence risk.

2.1.1 WEIGHT

There have been almost 20 studies on excess weight and colon cancer covering more than 3,000 cases, and there is consistent evidence of a positive association with obesity. In one meta-analysis of cohort and case control studies, there was a 15% increase in the risk of colon cancer for an overweight person (body mass index, BMI >25.0 kg/m2) compared with a person of normal weight and a 33% increase in risk for an obese person (BMI >30 kg/m2) compared with a person of normal weight (BMI 18.5-25.0 kg/m2).⁷ Evidence level 2++

The population of Scotland should be advised to maintain a body mass index of 18.5-25 kg/m2 throughout life.

2.1.2 FRUIT AND VEGETABLE CONSUMPTION

With regard to fruit and vegetable consumption, there have been six cohort studies, including more than 2,600 cases,⁸ and 22 case control studies made up of over 6,000 cases.⁹ The evidence from the case control studies consistently supports an inverse association between vegetable intake and colon cancer, although the evidence from the cohort studies, particularly the most recent ones, is less convincing. The role of dietary fibre has also been widely studied, but the cohort studies suggest no clear association between fibre intake and colorectal cancer, and the results of case control studies have been inconsistent.^{9, 10} Furthermore, a small number of randomised controlled trials (RCTs) of wheat bran supplements provide little support for a protective effect against recurrence of colorectal adenomas.¹¹ Evidence level 2++

Individuals in Scotland should be advised to eat five or more portions of fruits and vegetables a day, in line with the current guidance from the Health Education Board for Scotland.

2.1.3 MEAT CONSUMPTION

Two meta-analyses of meat consumption were identified, one based on cohort studies only,¹² the other based on both case control and cohort studies.¹³ The cohort studies include around 3,500 newly incident cases, and the case control studies around 16,000 cases. The association between total meat consumption and colorectal cancer is inconsistent, and both meta-analyses show no statistically significant overall association. There is considerable heterogeneity between the results of case control studies.¹³ In the cohort studies in which a positive association was found, the possibility that confounding factors might account for the results has not been excluded.¹² Data on red meat and processed meat suggest positive associations with the risk for colorectal cancer. However, the volume of evidence on these is substantially less than for total meat consumption, and it is possible that publication bias has favoured positive results. For these reasons it is not possible to make a recommendation on the restriction of meat consumption. Evidence level 2++

2.1.4 BETA-CAROTENE

Data on colorectal cancer are available from two randomised trials of beta-carotene with or without other agents in the prevention of cancer and 11 observational studies of colorectal cancer and serum or plasma concentration of beta-carotene.¹⁴ These do not support a role for beta-carotene in the prevention of colorectal cancer. Evidence level 2++

2.2 Physical activity

Approximately 50 case control or cohort studies of physical activity and colorectal cancer have been carried out, including more than 13,000 cases of colon cancer. These studies indicate a consistent inverse relationship, with a 50% reduction in risk among those with the highest level of physical activity.^{15, 16, 17, 18} The relationship appears to be stronger in men, and the effect seems to be restricted to colon cancer, with little effect of exercise on rectal cancer in men or women. Evidence level 2++

The population of Scotland should be encouraged to take at least 30 minutes of physical activity (such as brisk walking) on most days, citing decreased colorectal cancer risk as one of the reasons.

2.3 Smoking

Although earlier studies of smoking and colorectal cancer showed no association, in more recent studies long term smokers have been found to be at elevated risk, with relative risks typically in the range of 1.5 to 3.0.¹⁹ The temporal pattern of the studies is consistent with an induction period of 30 to 40 years, and the emergence of an association for men before women is consistent with the pattern of smoking uptake occurring earlier in men in many countries. It has been estimated that one in five colorectal cancers in the USA might be attributed to tobacco use,¹⁹ and reducing the amount of smoking in the population may have effects on colorectal cancer as well as on other adverse outcomes of smoking. Evidence level 2++

The population of Scotland should be encouraged not to smoke, citing decreased colorectal cancer risk as one of the reasons.

2.4 Alcohol

The association between colorectal cancer and alcohol intake is not clear. Although the majority of studies suggest a positive association between alcohol consumption and colorectal cancer, a substantial proportion of studies show no association.⁹ In a recent meta-analysis there was significant heterogeneity in the relationship between colon cancer and alcohol intake between the cohort and case control studies included, and for the studies of rectal cancer there was significant heterogeneity by study quality and gender.²⁰

Although the consumption of alcohol in moderation is beneficial to cardiovascular health in men over 40 and postmenopausal women, specific advice about alcohol cannot be given in the context of colorectal cancer prevention.

2.5 Hormone therapy

Protective effects of both hormone replacement therapy (HRT) and oral contraceptives (OC) have been postulated. The majority of evidence, especially that from more rigorously designed studies, shows an inverse relationship between postmenopausal oestrogen replacement therapy and colorectal cancer.^{21, 22} In all four available meta-analyses, there was significant heterogeneity in the magnitude of the effect between studies.^{23, 24, 25, 26} One randomised trial has shown a reduction in risk for colorectal cancer and hip fractures, but this risk reduction was outweighed by increased risk for coronary heart disease (CHD) events, strokes, pulmonary embolism and invasive breast cancer.²² The relative risks appear to be lower for current than for past users. The protective effect reduces several years after stopping hormone use,²⁴ and there appears to be no association with rectal cancer.²⁶ Fewer data are available on OC use, although recent, rather than long term intake appears to be related to some risk reduction.²⁷ Despite consistent findings, there is concern that unidentified confounding factors or the “healthy user effect” may have influenced the observed effect, and there is lack of information on the influence of hormone type, dose and duration of use. Evidence level 1+,2++

The use of hormone replacement therapy specifically to prevent colorectal cancer is not recommended.

2.6 Chemoprevention using NSAIDS

The weight of evidence (covering more than 18,000 cases) for a protective effect of aspirin use against colorectal cancer, and the consistency of the effect in studies differing in design, location, population and motivating hypothesis means that chance alone cannot explain the inverse relation between aspirin use and colorectal cancer.²⁸ Detection bias, bias due to indications for use of aspirin, other confounding factors, problems in the measurement of aspirin use and publication bias individually would not provide a reasonable explanation for the findings, although a possible cumulative effect of these issues cannot be completely excluded. The evidence relating to other types of non-steroidal anti-inflammatory drug (NSAID) is much less substantial.²⁸ Evidence level 2++

Detailed consideration of the total benefits in the prevention of colorectal cancer and other diseases in relation to toxicity will be required before use of aspirin in the prevention of colorectal cancer can be recommended.

2.7 Screening

Screening is the term used to describe the investigation of asymptomatic individuals in order to detect disease at an early stage when it is more amenable to treatment. In colorectal cancer screening may be applied to populations (limited only by age range) or to high risk groups. In this section, the high risk groups considered are those who have had adenomas or inflammatory bowel disease diagnosed. Patients who have had colorectal cancer are dealt with in section 10, and those with a family history are discussed in section 4.

2.7.1 POPULATION SCREENING

Because of the high incidence of colorectal cancer, screening an appropriate age range within an entire population has been the subject of high-quality research in several Western countries. The most widely investigated screening modality has been faecal occult blood testing (FOBT), and a meta-analysis of four randomised controlled trials and two non-randomised trials of around 443,000 people aged 40 or over in five countries has been carried out.²⁹ This concluded that FOBT screening resulted in a 16% reduction in colorectal cancer mortality, and when adjusted for attendance for screening, this improved to a 23% reduction. Evidence level 1++

There is now evidence from a long-running randomised trial, based in Minnesota, that FOBT screening results in a reduction in the incidence of colorectal cancer, presumably owing to the detection and removal of adenomas.³⁰ Evidence level 1+

Other modalities, notably colorectal endoscopy have been put forward as screening tests, and once-only flexible sigmoidoscopy is the subject of a large UK randomised trial, but mortality data will not be available from this study until 2007.³¹

A demonstration pilot of FOBT screening in 50-69 year-olds is underway in two populations in Scotland (Grampian, Tayside & Fife) and England (Coventry and Warwickshire), covering a total population of around two million.³² This is being externally assessed in order to ensure that the short term outcomes of the randomised trials can be reproduced in large, representative populations, and that the necessary quality in investigation and treatment can be delivered. A decision regarding a national colorectal screening programme will be informed by the results of this pilot.

2.7.2 SCREENING PATIENTS WITH INFLAMMATORY BOWEL DISEASE

It is generally accepted that patients with long-standing ulcerative colitis are at higher risk of developing colorectal cancer than the general population. Although this risk is hard to quantify, a meta-analysis of 116 studies estimated the overall incidence of colorectal cancer in any patient with ulcerative colitis to be 3.7%, with cumulative probabilities of 2% by 10 years, 8% by 20 years and 18% by 30 years. There was no measurable association between extent of disease and level of risk.³³ In addition to ulcerative colitis, Crohn’s colitis is also recognised as a risk factor, and there is evidence that the cumulative risks of developing colorectal cancer in the two disease processes are similar.³⁴ Evidence level 1++,2++

Despite the lack of direct evidence that screening inflammatory bowel disease patients reduces mortality from colorectal cancer there is consensus that some form of colonoscopic surveillance is appropriate for individuals with long-standing disease. It is common practice to perform colonoscopy every one to two years beginning eight years after the onset of pancolitis and 15 years after the onset of left-sided colitis³⁵ but, given the evidence cited above, a different regimen may be more appropriate. If colonoscopy is to be valuable, in addition to biopsy of suspicious lesions, it is important that mucosal biopsies are taken to look for dysplasia; 40% of patients with high grade dysplasia either have colorectal cancer or develop it within a short time interval.³⁶ Evidence level 4

Patients with left-sided colitis or pancolitis of 10 years duration should undergo three yearly colonoscopy with mucosal biopsies and biopsy of any suspicious lesions. The frequency of examination should increase to yearly when the disease has been present for 20 years, or when indeterminate dysplasia has been diagnosed.

Colectomy should be performed for high grade dysplasia, and considered for low grade dysplasia.

2.7.3 SCREENING PATIENTS AFTER REMOVAL OF ADENOMATOUS POLYPS

The majority of colorectal cancers arise from adenomatous polyps and it follows that these lesions should be removed.³⁶ There is good evidence that this policy reduces the risk of developing colorectal cancer. ^{30, 35} Evidence level 1+,4

Once an individual has been found to have one or more adenomas, follow up colonoscopy to seek and remove further polyps is advised by most authorities. The National Polyp Study has shown that three yearly colonoscopy is as effective in detecting adenomas with advanced pathological features as yearly examination.³⁵ The risk of recurrent polyps appears to be greater when multiple polyps are found at the first colonoscopy or if the index polyp has a villous or severely dysplastic component³⁷ Patients with one or two tubular adenomas without severe dysplasia are just as well served by follow up colonoscopy at five years.³⁸ Evidence level 1+,2+

Patients who have undergone colonoscopic polypectomy for adenomas should be offered follow up colonoscopy. If one or two adenomas <1 cm are found at colonoscopy, a repeat colonoscopy should be performed at five years. If this is normal, colonoscopic surveillance may cease. If there are three or more adenomas, or at least one >1 cm, or at least one showing severe dysplasia, repeat colonoscopy should be performed at three years. If surveillance colonoscopy is subsequently normal on two consecutive occasions, it may cease.

If there is uncertainty regarding completeness of adenoma removal owing to the presence of multiple adenomas or technical difficulties with the examination it may be appropriate to offer follow up colonoscopy at one year or sooner.

Colonoscopic follow up should continue until the age and fitness of the patient dictate that it should cease.

This decision should result from a consensus between the patient and the doctor.

2.7.4 PSYCHOLOGICAL CONSEQUENCES OF SCREENING

The psychological consequences of screening have not been systematically assessed. One RCT in Norway, in which healthy people were screened, identified no short term adverse psychological effect.³⁹ Another RCT in the UK looked at the effect of information about cancer screening on those about to be screened and found no adverse effects.⁴⁰ Evidence level 1+

The long term effects of screening, such as reassurance in cases of false negative tests or increased distress in anxious individuals have not been studied.