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Bowel cancer risk factors

This section contains information on bowel cancer and diet, focusing on meat and fish, fibre, fruit and vegetables, fat, dairy, sugar, folate and selenium, vitamins B6 and B12, calcium and vitamin D (including supplements). It also details the evidence on bowel cancer risk and obesity, physical activity, alcohol and tobacco, NSAIDS, statins, HRT and oral contraceptives, other medical conditions, radiation, and family history. Overall, it has been estimated that around 57% of bowel cancer cases in men and 52% in women in the UK are linked to lifestyle and environmental factors.1

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.2

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Meat and fish

There is strong and consistent evidence that eating red and processed meat increases bowel cancer risk, but more evidence is needed to clarify whether eating fish (and perhaps which types of fish) reduces bowel cancer risk. The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Colorectal Cancer Report 2010 concluded that “The evidence that red meat [and] processed meat... are causes of colorectal cancer is convincing” but that “Evidence for foods containing fish is less consistent and no conclusion could be drawn”.3

At least four meta-analyses have shown a 17-30% 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 25-50g/day of processed meat.4-7 A pooled analysis of UK case-control studies found no effect of 50g/day red or processed meat, but the number of participants was relatively small (less than 600 bowel cancer patients) and the amount of red/processed meat they consumed was relatively low.8 In most studies, red meat is defined as beef, veal, pork, mutton and lamb (fresh or frozen); and processed meat is defined as meat preserved in any way other then freezing, including ham, bacon, sausages, pate and tinned meat.

In 2011, it was estimated that around 21% of bowel cancers in the UK in 2010 were linked to consumption of red and processed meat.9 Red meats contain haem iron, and there is limited evidence that iron consumption is associated with higher bowel cancer risk.3

A 2007 meta-analysis found a 3% decrease in bowel cancer incidence for every 100g fish eaten per week, but this effect was not statistically significant.10 A meta-analysis two years later,11 and more recent large cohort studies in Japan 12 and America,13 have found no association between fish consumption and bowel cancer incidence. However, there may be a modest risk reduction for rectal cancer, according to a more recent meta-analysis.127

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Fibre

The evidence for a protective effect of fibre has strengthened in the last few years and overall shows that intake of dietary fibre (particularly from cereals and whole grains) reduces bowel cancer risk, though the type of fibre, range of fibre intakes observed, way fibre intake is measured and specific sites of cancer within the bowel may affect the findings of some studies. The WCRF/AICR 2010 Report concluded that “The evidence that consumption of foods containing dietary fibre protects against colorectal cancer is convincing”.3

A 2011 meta-analysis of 25 prospective studies involving almost two million participants found that bowel cancer risk was reduced by 10% for every 10g/day total dietary fibre and cereal fibre.14 90 g/day of whole grains accounted for around a 20% reduction in bowel cancer risk – this is three servings, equivalent to three slices of 100% whole grain bread. However this review found no association between fruit or vegetable fibre and risk of colorectal cancer. In 2011, it was estimated that around 12% of bowel cancer cases in the UK in 2010 were linked to people eating less than 23g/day of fibre.15

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Fruit and vegetables

The WCRF/AICR 2010 Report concluded that “The evidence that non-starchy vegetables [and] fruits ... protect against this cancer is limited”, because though the evidence base is substantial, findings are inconsistent.3

A 2011 meta analysis, pooling data from over 1.5 million participants, found that colon cancer risk was reduced by 2% for every 100g/day of vegetables consumed.16 This analysis also found that increasing fruit or vegetable intake from very low levels up to about 100-200g/day served to reduce bowel cancer risk by about 10%, but there was little further reduction in risk with higher intakes. Most studies in this analysis adjusted for other lifestyle factors relevant to risk of bowel cancer and associated with levels of fruit and vegetable intake (e.g. physical activity, smoking, bodyweight, alcohol intake and red and processed meat intake), and there were no significant differences in findings between studies which did and did not adjust for these factors.

However, a 2003 review by the International Agency for Research on Cancer (IARC) concluded that the risk reduction from fruit and vegetable consumption was so modest that confounding could not be ruled out as an explanation for the observed association.17

The WCRF/AICR 2010 Report concluded that “Consumption of garlic... probably protects against this cancer”.3 Epidemiological evidence for a protective effect of garlic is limited but some large trials and studies with animals point to a benefit. A 2009 systematic review concluded that there is “very limited credible evidence for a relation between garlic consumption and reduced colon cancer risk” as most epidemiological studies have found no significant effects;18 however a 2007 systematic review concluded that garlic probably protects against bowel cancer, based on a randomised controlled trial of garlic extract in bowel cancer patients, and studies with animals.19 Pooled epidemiological evidence shows that eating 5-6 cloves of raw or cooked garlic per week reduces the risk of bowel cancer by around 30%, though this analysis excluded the largest study that showed no association, which means the results may not be reliable.20 Most studies have looked at the effect of dietary garlic rather than garlic supplements.

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Fat

The level of fat in a person’s diet appears to have no independent impact on their risk of bowel cancer, though common components (e.g. meat) and consequences (e.g. obesity) of a high-fat diet do increase bowel cancer risk. The WCRF/AICR 2010 Report concluded that “The evidence that foods containing animal fats are causes of this cancer is limited”.3

A 2011 meta analysis combining data from over 450,000 participants found no independent association between dietary fat intake and bowel cancer incidence, either for participants grouped together or for different genders, ethnicities, countries and age groups analysed separately.21

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Dairy

The evidence shows consumption of milk probably reduces bowel cancer risk, but consumption of cheese may increase risk. The WCRF/AICR 2010 Report concluded that “Consumption of milk probably protects against this cancer” and that “The evidence that cheese causes this cancer is limited”.3

A systematic review in 2011 pooling data from almost 1.2 million participants found colon (but not rectal) cancer risk was reduced by 16% per 400 g/day of total dairy products consumed (1 pint/0.5 litres of semi-skimmed milk weighs approximately 550g).22 There was evidence that the benefit of dairy consumption in reducing bowel cancer risk overall was only seen at levels of consumption over 100g/day. 200g of milk per day was associated with a 9% decrease in colon cancer risk, but a reduction of risk for bowel cancer overall only became apparent when more than 200 g/day of milk was consumed. At 500-800 g/day of milk, bowel cancer risk was reduced by 20-30%. Most of these studies adjusted their estimates of the effect of dairy on bowel cancer risk to take account of the effects of a range of other relevant factors, including calcium, fibre, alcohol and red meat intake, body mass index, smoking, education and physical activity. These estimates are in line with those from a 2004 meta-analysis which found consuming 250g/day of milk reduced the risk of distal colon and rectal cancer by 15%, in comparison with the risk for people consuming less than 70g/day.23

In the 2011 analyses, milk appeared to be the most beneficial type of dairy for reducing bowel cancer risk, as intake of cheese and other dairy products (e.g. cottage cheese, yogurt, butter and ice-cream) showed no independent significant effects on risk. However, the number of included studies was smaller for these products than for milk. The WCRF/AICR 2010 report concluded that there is ‘limited-suggestive’ evidence that cheese increases the risk of bowel cancer. A recent cohort study with over 45,000 Italian participants (around 200 of whom developed bowel cancer) found eating on average 65g/day (men) or 98g/day (women) yogurt (versus eating no yogurt at all) reduced bowel cancer risk by 53% for men and 31% for women, even when other relevant factors were adjusted for in the analysis.24 The results were only borderline significant for women in fully adjusted models.

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Sugar

It remains unclear whether dietary sugar intake is associated with bowel cancer risk. The WCRF/AICR 2010 Report concluded that “Evidence suggesting that consumption of foods containing sugar is a cause of colorectal cancer is limited”.3

Two meta-analyses have explored dietary sugar intake measured as glycaemic index or glycaemic load and colon cancer risk.25,26 These analyses were conducted within a year of one another and with almost identical groups of source studies, however the first found an 18-26% risk increase for the highest versus lowest sugar intake categories,25 whilst the second found no association between sugar intake and colon cancer risk.26 The first analysis adjusted for study design whilst the second did not, and the second included a large cohort study which observed no association between sugar intake and colon cancer risk. A more recent pooled analysis which explored the effect of sugar-sweetened carbonated soft drinks found no effect on colon cancer incidence.27

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Folate and selenium

Folate (a water-soluble B vitamin) appears to protect against bowel cancer, but it remains unclear whether the same level of benefit is derived from dietary folate (from food, particularly fruit and vegetables) and synthetic folate (folic acid supplements).  Selenium can be obtained in food (particularly brazil nuts) and supplements; evidence for its effect on bowel cancer risk is mixed. The WCRF/AICR 2010 Report concluded that “Evidence for foods containing folate... and selenium... is less consistent and no conclusion could be drawn”.3

A 2011 meta-analysis of 27 studies found that high versus low total folate intake (dietary plus supplements) was associated with a 15% reduction in bowel cancer risk; however the effect was significant only for case-control studies, and was not significant for cohort studies of dietary folate alone.28 Conversely, a 2010 systematic review of randomised controlled trials of folic acid supplementation found no significant effect of folic acid on bowel cancer risk,29 and a 2005 meta-analysis found a 25% reduction in bowel cancer risk with high versus low dietary folate intake, but no significant effect for total folate.30 A 2009 meta-analysis of 3 studies found no effect of taking folic acid supplements for less than 3 years, but showed that taking folic acid supplements for three years or more increased the risk of pre-cancerous bowel adenomas and bowel cancer by 35%,31 and a large nested case-control study reported a significant increase in risk of bowel cancer in people with higher circulating levels of folate.32 Some experts have proposed that folate plays a dual role in bowel cancer in which moderate dietary intake before development of pre-cancerous adenomas reduces risk of adenoma development, but increased folate intake once adenomas have developed increases risk of cancer.33 However, findings are somewhat mixed, with the 2010 review finding no significant effect of folic acid versus placebo on adenoma recurrence or advanced adenoma incidence in people with a history of adenomas,29 and a large prospective study showing a 31% reduction in bowel cancer risk for people with the highest overall folate intake 12-16 years before diagnosis, but no effect of intakes in the more recent past.34

The US Government was sufficiently convinced of the health benefits (and absence of risk) from folic acid that it introduced mandatory folic acid fortification of grain products in 1997, and a recent large cohort study found that 8.5 years on, higher total folate intake (including intake specifically from supplements) was associated with a decreased bowel cancer risk.35

A 2011 meta analysis found men with the highest concentrations of selenium in the blood had 32% lower bowel cancer risk compared with men with the lowest concentrations, but found no association between selenium level and bowel cancer risk in women.36 A 2004 pooled analysis found a similar level of risk reduction for both sexes combined.37 However, at least three other recent reviews have found no significant effect of selenium on bowel cancer risk.29,38,39

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Vitamins B6 and B12

Though research into the relationship between vitamin B6 and bowel cancer has only gathered pace in recent years, what evidence there is suggests B6 may lower bowel cancer risk.

A 2010 systematic review with over 5,000 bowel cancer cases found that the risk of colorectal cancer almost halved with every 100-pmol/mL increase in the active form of vitamin B6 (Pyridoxal 5'-phosphate; PLP) in the blood, although there was no significant risk reduction for having a higher intake of vitamin B6 from diet and/or supplements.40 There is some evidence that B6 may actually increase rectal cancer risk.41

Most studies have found no association between levels of vitamin B12 and colorectal cancer risk,42-44 though there is some evidence that having higher levels of vitamin B12 reduces risk of rectal cancer.45,46

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Calcium and Vitamin D

Calcium and vitamin D supplements probably serve to reduce bowel cancer risk when taken in conjunction; however current evidence suggests that calcium alone has little effect on bowel cancer risk in the general population because vitamin D is essential for adequate calcium absorption. The WCRF/AICR 2010 Report concluded that “Consumption of calcium probably protects against this cancer”.3

Two meta analyses of randomised controlled trials (RCTs) published in 2010 found calcium supplements had no effect on bowel cancer risk in the general population, or on the risk of advanced adenomas in people with a history of adenomas.29,47 However these reviews found calcium intake was associated with an 18-20% reduction in risk of adenoma recurrence in people with a history of adenoma. A Cochrane review updated in 2010 drew no conclusions on the relationship between calcium supplements and bowel cancer risk because the number of cases was so small, but found that the risk of adenoma recurrence was reduced by 26% in supplemented participants.48

A 2004 meta analysis of cohort studies reported quite different findings, showing people with the highest levels of total calcium intake (from foods and supplements) reduced their risk of bowel cancer by 22% in comparison with people in the lowest intake group. This review found that intake of calcium through the diet alone had a lesser effect, reducing bowel cancer risk by 14%.23 In a large randomised controlled trial, vitamin D intake modified the association between calcium intake and bowel cancer risk, with the risk reduction limited to individuals with relatively high intakes of both nutrients.49 Vitamin D is essential for the normal absorption of calcium, and many cohort and case-control studies have explored the effect of supplementing both together, though most RCTs have looked at calcium supplementation without vitamin D, which may explain the different findings between reviews of the different study types.

The impact of vitamin D on health outcomes is often assessed from levels of 25(OH)D, which is circulating vitamin D in the blood. This is the truest measure of vitamin D status, as we get most of our vitamin D from exposure to sunlight rather than from foods or supplements. Three meta analyses explored the impact of 25(OH)D on bowel cancer and colorectal adenoma incidence in 2010 and 2011.50-52 One found people in the highest categories of vitamin D intake had a 12% lower risk of bowel cancer than did people in the lowest intake categories, and every 10 ng/mL increase in levels of was associated with a 26% decreased bowel cancer risk.50 Another found the risk of colorectal adenomas was reduced by 18% for every 20 ng/mL increase in 25(OH)D.51 A third reported a slightly lower risk reduction for bowel cancer of 15% per 10ng/mL 25(OH)D.52

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Diet summary

There is convincing evidence that dietary fibre protects against bowel cancer. Garlic, milk, and calcium probably also have a protective effect. Vegetables, fruits and dietary vitamin D may offer some reduction in bowel cancer risk, but evidence is limited.3

There is convincing evidence that eating red and processed meat increases the risk of bowel cancer. It is possible that eating cheese, foods containing iron, foods containing animal fats, and foods containing sugars may also increase risk, but evidence is limited. It remains unclear on current evidence whether folate, fish, and selenium affect bowel cancer risk.3

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.53

Between 1974 and 2009 in the UK there was a fall in the consumption of potatoes accompanied by an increase in consumption of fresh fruit and a steady consumption of vegetables (excluding potatoes), and meat, as Figure 5.1 shows.54

 

Figure 5.1: Household food consumption, Great Britain, 1974 - 2009

Almost three quarters of the adult population in England is still falling short of the recommended five portions of fruit and vegetables a day (Figure 5.2).55 For UK adults, the proportion failing to eat five a day is slightly lower, at around two-thirds. Adults aged 65 and older are more likely to eat 5 a day than are younger adults, and only 10% of 11-18 year-olds eat their 5 a day.56

Figure 5.2: The number of portions of fruit and vegetables eaten per day by adults aged 16 and over, England, 2009

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Obesity

Obesity is associated with an increased risk of colon cancer, particularly for men. Meta analyses show the risk of colon cancer increases by an estimated 24-30% per 5kg/m2 increase in body mass index (BMI) for men.57-59 In comparison to healthy-weight men (BMI less than 25 kg/m2), overweight men (BMI 25-29.9kg/m2) have a 23% higher risk of colon cancer, and obese men (BMI 30kg/m2 or more) have a 53% higher risk.60 The association is weaker in women, with colon cancer risk increasing by 9-12% per 5kg/m2 BMI increase,57-59 and the association proving non-significant in one meta analysis.60

Larger waist size has been associated with increases in colon cancer risk in men (33% risk increase per 10cm waist circumference increase) and women (16% risk increase per 10cm waist circumference increase), as has increasing waist-to-hip ratio in both men (43% risk increase per 0.1-unit increase in ratio) and women (20% risk increase per 0.1 unit increase in ratio).59

Higher BMI is linked less strongly to higher rectal cancer risk: a 5kg/m2 BMI increase is associated with a 9-12% higher rectal cancer risk for men (obese men have a 27% higher rectal cancer risk than healthy-weight men 60), but with no effect on rectal cancer risk in women.58-59

The female sex hormone oestrogen may modify the association between BMI and colorectal cancer risk in women but the exact nature of this relationship is unclear. Some studies have found being overweight is linked with higher risk of bowel cancer among premenopausal women only,61 or among premenopausal women and among postmenopausal women taking hormone replacement therapy (HRT), but has no effect on cancer risk among postmenopausal women not taking HRT.62 Other studies have found the opposite; the increased risk of colorectal cancer with increasing BMI or waist size is apparent in postmenopausal women not taking HRT, but not in HRT users.60,63,64

The prevalence of obesity has increased in adults in England as shown in Figure 5.3.55 New figures for the UK show that 71% of men and 58% of women are overweight (BMI of 25 or more).56

Figure 5.3: Trends in body mass index by sex, England, 1993 and 2009

Between 1993 and 2009 the percentage of obese men in England rose from 13 to 22% and for women from 16 to 24%.55 In 2011, it was estimated that 13% of bowel cancers in the UK in 2010 were linked to overweight or obesity.65

Some questions have been raised about whether looking at BMI trends gives an accurate picture of bodyweight, as BMI is not an appropriate measurement for some individuals, for example people who are muscular. However, trends in waist circumference in adults (Figure 5.4) in England give a similar picture of increasing prevalence of overweight.55

 

Image showing trends in waist circumference, adults, England

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Physical activity

Three recent meta-analyses show that people who are more physically active are at lower risk for colon cancer, but physical activity levels appear to have no significant effect on rectal cancer risk.11,66,67

Overall, the evidence shows that the most active men can reduce their risk of colon cancer by 19-28%, and the most active women can reduce their risk by 11-32%, in comparison with the least active.11,66,67

The risk of colon adenoma is reduced by 16% and the risk of advanced adenomas is reduced by 30% in the most active people compared to the least active.68 It was estimated in 2011 that more than 5% of colon cancers in the UK in 2010 were linked to people doing less than 150 minutes of at least moderate intensity physical activity per week.69

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Alcohol and tobacco

Alcohol intake increases bowel cancer risk, even at quite moderate levels of consumption. A 2011 systematic review reported a 21% risk increase for both colon and rectal cancers with an alcohol intake of around 1.6-6.2 UK units per day (1.6 units is less than one standard glass of red wine or around half a pint of beer), compared to non-/occasional drinkers.70 This review also found a 52% risk increase with an intake of 6.2 units (3 glasses of wine or 2 pints of beer) per day or above, again compared to non-/occasional drinkers. Dose-response analysis within this review showed a 7% increase in risk for every 10g/day (approximately 1 unit) alcohol consumed.70 It was estimated in 2011 that more than 11% of bowel cancer cases in the UK in 2010 were linked to alcohol consumption.71

Cigarette smoking increases bowel cancer risk, according to four meta-analyses in this area,11,72-74 and a 2009 IARC statement that there is sufficient evidence that smoking causes cancer of the bowel.122 Two meta-analyses which included only prospective cohort studies found that current cigarette smokers have a 20-21% higher risk of bowel cancer than people who have never smoked;11,72 however the other two, which included some case-control studies, found this effect was not statistically significant.73,74 Case-control studies reported lower risk estimates than did cohort studies.73 Three meta-analyses explored the effect of having previously smoked on bowel cancer risk, and all three found ex-smokers’ risk was higher than people who have never smoked, by 17-25%.72-74 Only one of the meta-analyses explored the risk for former and current smokers combined (ever-smokers), and found their bowel cancer risk was 18% higher than that of never-smokers.73 Three meta-analyses assessed the effect of smoking on bowel cancer risk for males and females separately and found a 18-38% risk increase for smoking men, and a non-significant 5-9% risk increase for smoking women, in comparison with never-smokers.11,72,73 All four meta-analyses found smoking had a greater effect on rectal cancer risk than colon cancer risk. Bowel cancer risk increased steadily with the number of cigarettes smoked per day (around 7-11% increase in risk for every 10 cigarettes,73 and 18% increase for 20 cigarettes a day 11,74), and the number of cigarettes smoked altogether (around 9% risk increase for every 10 years of smoking one pack per day 74). One analysis found the younger a person starts smoking, the greater the impact on their bowel cancer risk.74

Current smokers have also been shown to have just over twice the risk of colorectal adenomatous polyps, compared with never-smokers.75

A study published in 2011 estimated that around 8% of bowel cancers in the UK in 2010 were caused by smoking.76

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Nonsteroidal anti-inflammatory drugs (NSAIDs)

A recent analysis of results from two randomised trials in the UK and Sweden showed that low-dose aspirin (75 mg/day) taken for between 1 and 8.6 years is associated with a 39% reduction in risk of death from colon cancer.77 This study and a subsequent analysis of eight randomised trials also found that there was no additional benefit to taking more than 75mg/day.77,78 Regular aspirin also protects against death from bowel cancer, reducing risk by 42% according to a meta-analysis of randomised trials.126

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.79 Two randomised trials confirmed that aspirin reduces risk of colorectal adenomas.80,81 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.

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Statins

The evidence on statins and bowel cancer risk remains mixed. Meta analyses and systematic reviews show that taking statins to reduce blood cholesterol has no significant effect on bowel cancer risk in cohort studies and randomised trials,82-84 however one meta analysis found a small protective effect for bowel cancer observed in case-control studies.82 A recent large US cohort study found a 21% reduced bowel cancer risk in postmenopausal women taking statins for three years or more,85 but a recent large UK case-control study found that use of statins for 4 years or more was associated with a 23% increase in bowel cancer risk.86

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Hormone replacement therapy (HRT) and oral contraceptives (OCs)

The evidence on HRT and colorectal cancer risk is mixed, with some evidence of differences by the specific hormones involved, cancer site (colon or rectum), and current and former use. There is more evidence for oestrogen-only HRT and this evidence probably supports a protective effect. OCs appear to have a protective effect though more recent studies have tended toward null findings.

Three meta-analyses published in the late 1990s (therefore including mainly studies of oestrogen-only HRT 87) examined the association between HRT use and colon, rectum or overall bowel cancer. One reported that women who had ever used HRT had a 19-20% reduction in risk of colon and rectum cancers, and women currently using HRT had a 34% reduction in the risk of all bowel cancer;87 another found use of HRT at any time was linked with 15% lower colon cancer risk, and women currently or recently using HRT had a 31% lower colon cancer risk;88 the third found a 33% reduction on colon cancer risk only among women recently using HRT, but no effect of HRT use on rectal cancer risk.89

More recently studies have looked at both oestrogen-only and combined oestrogen-progestin HRT, with mixed results. Oestrogen-only HRT was found to have no effect on bowel cancer risk in a large cohort study 90 and a randomised trial,91 but a significant risk-reducing effect in a large nested case-control study (particularly when HRT was taken transdermally)92 and a large prospective study (for current but not former use).93 Combined HRT did not affect bowel cancer risk in the two large cohort studies 90,93 and did not reduce colon cancer risk significantly in a randomised trial of women with pre-existing cardiovascular disease,94 but reduced risk by 44% after five years of use in another randomised trial.95

Women who have ever used OCs have a 19% reduced risk of colorectal cancer, according to the results of a 2009 meta-analysis.96 This analysis also found a trend for stronger effects with more recent use, though this was based on a small number of studies.96 A large cohort study published since this meta analysis found ever-use of OCs significantly reduced bowel cancer risk only for postmenopausal women,97 and a 2010 case-control study found no effect for OC use on distal bowel cancer risk.98

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Other medical conditions

The risk of bowel cancer is higher in people with ulcerative colitis, a type of inflammatory bowel disease.99 A meta analysis showed that ulcerative colitis patients have a 2% risk of developing bowel cancer after 10 years of colitis, an 8% risk after 20 years, and an 18% risk after 30 years.100 Two meta analyses show Crohn’s disease patients have between 2 and 3 times the bowel cancer risk of the general population,101,102 though one of these reviews indicates cancer risk is only elevated for patients with lesions of the colon and not for patients where only the ileum is affected.102

Four meta-analyses have reported a significant 27-30% increased risk of colorectal cancer in type II diabetes (diabetes mellitus) patients.103-106 Three of these analyses have shown the effect is similar for males and females,103-105 but one has shown that diabetes increases bowel cancer risk by almost 50% for men but increases it by less than 10% for women.106  A diabetes drug called metformin is associated with a 36% decrease in bowel cancer risk, compared with diabetics not receiving this medication, a meta-analysis showed.123

There is some evidence that people who have had their gallbladder removed may have a modest increase in bowel cancer and colorectal adenoma risk.107-109 However, not all studies have shown an association.110,111,124,125 Gallstones may also be associated with increased risks of rectal cancer and adenomatous polyps in the colon; given that people who have their gallbladder removed usually have gallstones, this may be a mechanism for the association between gallbladder removal and bowel cancer.124,125

Anal cancer (ICD10 C21) has been linked to infection with the human papillomavirus (HPV), with HPV16 being the most prevalent type detected in invasive anal cancer.112 It has been estimated that around 90% of anal cancers are linked to HPV infection, or around 890 cases in the UK in 2010. This is equivalent to around 2% of all bowel cancer cases.113

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Radiation

A study published in 2011 estimated that more than 1% of bowel cancers in the UK in 2010 were linked to radiation exposure. The majority of the attributable cases (around 500) were linked to diagnostic radiation, while around 85 cases were attributed to radiotherapy for a previous cancer and around 35 cases to background radiation.114

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Family history

About 5% of bowel cancers are linked to familial adenomatous polyposis (FAP), the polyposis syndromes and hereditary non-polyposis colorectal cancer (HNPCC).115 FAP probably accounts for less than 1% of bowel cancers,99 and is characterised by the presence of multiple adenomas in the bowel, and FAP patients have almost 100% risk of developing bowel cancer by their 40s.116 HNPCC is estimated to be responsible for 1-4% of colon cancers and is characterised by early onset of bowel cancer.117 The risk for people with these mutations of developing colorectal cancer by age 70 is approximately 91% for men and 69% for women.118

Apart from these syndromes, hereditary factors are estimated to account for an additional 20% of colorectal cancer cases.115 Overall, people who have a first-degree relative with the disease are at approximately twice the average risk of bowel cancer,119,120 and at 70% greater than average risk of colorectal adenomas.121 The risk of bowel cancer is higher if the relative with the disease is young,119 or if there is more than one first-degree relative affected.119,120

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