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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

 

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 Around 21% of bowel cancers in the UK in 2010 were linked to consumption of red and processed meat, it is estimated.9

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.

WCRF/AICR classifies haem iron as possibly protective against bowel cancer, based on limited evidence.3 Haem iron (contained in red meats) is associated with a 12% increase in colon cancer risk per 1 mg/day, a meta-analysis showed.149

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

WCRF/AICR classifies dietary fibre as protective against bowel cancer.3 Around 12% of bowel cancer cases in the UK in 2010 were linked to people eating less than 23g/day of fibre.15

Bowel cancer risk is reduced by 10% for every 10g/day total dietary fibre and cereal fibre, a meta-analysis showed.14 90g/day of whole grains (equivalent to three slices of 100% whole grain bread) reduces bowel cancer risk by 20%.14 Fruit and vegetable fibre specifically is not associated with reduced bowel cancer risk.14

Bowel adenoma risk is reduced by 9% for every 10g/day total dietary fibre, with the strongest effect for cereal fibre, a lesser effect for fruit fibre, and no significant effect for vegetable fibre, a meta-analysis showed.145

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Fruit and vegetables

WCRF/AICR classifies non-starchy vegetables, and fruits, as protective against bowel cancer, based on limited evidence.3 IARC does not classify fruits or vegetables as associated with bowel cancer risk, concluding any link is so modest that confounding cannot be ruled out.17

Colon cancer risk is 2% lower per 100g/day of vegetables consumed, or 9-22% lower in those with the highest intake of cruciferous vegetables compared with those with the lowest intake, meta-analyses have shown.16,154,155

Colon cancer risk is 11% lower in those with the highest intake of fruits compared with those with the lowest intake, a meta-analysis showed.16

WCRF/AICR classifies garlic as probably protective against bowel cancer.3 Epidemiological evidence is very limited and overall indicates no effect, but an RCT and animal studies indicate some effect.18-20

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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

WCRF/AICR classifies milk as probably protective against bowel cancer, stating this is probably due to its calcium content.3 WCRF/AICR classifies cheese as a possible cause of bowel cancer, based on limited evidence, stating this may be linked with saturated fatty acids.3

Colon cancer risk is 9-15% lower per 200-250g/day of milk consumed, meta-analyses have shown.22,23 Bowel cancer risk is 20-30% lower per 500-800g/day of milk consumed, a meta-analysis showed.22

Cheese and other dairy product (e.g. cottage cheese, yogurt, butter and ice-cream) consumption is not associated with bowel cancer risk, a meta-analysis and large cohort study have shown.22,24

Bowel cancer risk is 8% lower per 300mg/day increase in total calcium intake (equivalent to 250ml milk), a meta-analysis showed.156 Bowel cancer risk is 9% lower per 300mg/day supplementary calcium intake, this meta-analysis showed.156 Bowel cancer risk may not be associated with non-dairy dietary calcium, a large cohort study indicated.24

Colon cancer risk may be 29% higher in people with the highest egg consumption, compared with those with the lowest, a meta-analysis showed.157

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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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Vitamins and minerals

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

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

Zinc

People with the highest zinc intake have a 20% decreased risk of colorectal cancer compared to those with the lowest zinc intake, a meta-analysis has shown.129

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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.

Bowel cancer risk is 15-26% lower per 10-20ng/mL increase in 25(OH)D (circulating vitamin D in the blood), meta-analyses show.50-52 This variability in observed effect sizes indicates modification by other factors such as adenoma/tumour stage or coexisting medical conditions.141,142

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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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Overweight and obesity

Body fatness and abdominal fatness are classified by WCRF/AICR as causes of colon and rectum cancer.3 An estimated 13% of bowel cancers in the UK are linked to overweight or obesity.65

Body mass index (BMI)

Bowel cancer risk is 33% higher in people who are obese by BMI, compared with those who are a healthy-weight, a meta-analysis showed.158 The association with BMI is stronger for men than women,57-60 and among women may vary with use of hormone replacement therapy (HRT) and menopausal status.60-64 The association with BMI is stronger for cancer of the distal colon than of the proximal colon or rectum,159 meta-analyses show.

Risk of colorectal adenoma is 47% higher in people who are obese by BMI compared with those who are healthy-weight, a meta-analysis showed.160

Abdominal fatness

Bowel cancer risk is 46% higher in people with the largest waist circumference, compared with those with the smallest, a meta-analysis has shown.158

Risk of colorectal adenoma is 39% higher in people with the largest waist circumference, compared with those with the smallest, a meta-analysis showed.161

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Physical activity

WCRF/AICR classifies physical activity as protective against bowel cancer (with evidence stronger for colon than rectum cancer).3 More than 5% of colon cancers in the UK in 2010 were linked to inadequate physical activity, it is estimated.69

The most physically active people have 14-30% lower risk of colon cancer, compared with those least physically active, meta-analyses show.66,67,146-148 Rectal cancer risk appears not to be associated with physical activity levels.66,146,148

Colon adenoma risk is reduced by 16% in the most active people compared to the least active, a meta-analysis shows.68

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Alcohol

Alcoholic beverages are classified by IARC and WCRF/AICR as a cause of colon and rectum cancers (WCRF/AICR classify the association as convincing for males and probable for females).3,162 An estimated 11% of bowel cancer cases in the UK are linked to alcohol consumption.71

Bowel cancer risk is 21% higher in people who drink 1.6-6.2 UK alcohol units per day, compared with non-/occasional drinkers, a meta-analysis showed.70 Bowel cancer risk is 52% higher in those who consume 6.2 units or more per day, compared with non-/occasional drinkers.70 Bowel cancer risk increases by 7% per unit of alcohol consumed per day.70

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Tobacco

Tobacco smoking is classified by IARC as a cause of colon and rectum cancers.162 An estimated 8% of bowel cancer cases in the UK are linked to tobacco smoking.

Bowel cancer risk is 20-21% higher in current cigarette smokers compared with never-smokers, meta-analyses of cohort studies have shown.11,72 The association is stronger in (perhaps limited to) males, stronger for rectal than colon cancer, and possibly limited to cohort studies.11,72-74 Bowel cancer risk is 17-25% higher in former cigarette smokers compared with never smokers, meta-analyses have shown.72-74

Bowel cancer risk increases with the number of cigarettes smoked per day, by 7-11% per 10 cigarettes per day, a meta-analysis has shown.73 Bowel cancer risk is higher in people who start smoking younger.74 Risk of bowel adenoma is around doubled by current smokers compared with never-smokers, a meta-analysis showed.75

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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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Medical conditions and treatments

Irritable bowel syndrome

Patients with irritable bowel syndrome (IBS) do not have an increased risk of bowel cancer in the long term, two large cohort studies have shown.150,151 They are 5-8 times more likely than the general population to receive a bowel cancer diagnosis in the period soon after their IBS diagnosis, probably reflecting increased medical monitoring in IBS patients, or initial misdiagnosis of bowel cancer as IBS.

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Inflammatory bowel disease

Bowel cancer risk is 70% higher in people with IBD (ulcerative or Crohn's colitis) compared with the general population, a meta-analysis has shown.99 Bowel cancer risk increases with extent and duration of IBD; patients who have IBD for 20 years or more have a 5% risk of developing bowel cancer.99,100 Bowel cancer risk may vary by location of IBD lesions.102

Bowel cancer risk is increased in patients with complicated diverticulitis, a meta-analysis and large cohort study showed, though uncomplicated diverticulitis does not increase risk.101,130

Bowel cancer risk is 4% lower in IBD patients treated with thiopurines, compared with IBD patients not receiving this treatment, a meta-analysis of cohort studies showed.152

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Gallbladder disease

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

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Diabetes

Bowel cancer risk is 22-30% higher in people with type II diabetes, compared with non-diabetics, meta-analyses show.103-106,134 The association between diabetes and bowel cancer risk may vary by type of treatment, though treatment type often relates to diabetes stage, which may further confound findings.

Metformin is associated with an 11-36% decrease in bowel cancer risk, while insulin is associated with a 37-61% increased risk, meta-analyses comparing users of these treatments with non-users showed.123,131-133

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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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Hypertension medications

Bowel cancer risk may be slightly decreased in users of angiotensin receptor blockers (ARBs), epidemiological studies indicate;163,164 however a meta-analysis of RCTs showed no association.165

Bowel cancer risk may be associated with use of angiotensin-converting enzyme (ACE) inhibitors, but evidence remains mixed.163,166

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Infections

Human papillomavirus (HPV)

Bowel cancer risk is around tenfold higher in people with Human papillomavirus (HPV) infection, compared with uninfected people, a meta-analysis showed.135

H Pylori

Bowel cancer risk is 39% higher in people with H Pylori infection, compared with uninfected people, meta-analyses have shown.136,137 Colon cancerrisk is 30% higher in people with H Pylori.136,137

Humman immunodeficiency virus (HIV)

Bowel cancer risk is not associated with human immunodeficiency virus (HIV)infection, meta-analyses and a cohort study show.138-140

Anal cancer

HIV type 1 and HPV type 16 are classified by IARC as causes of anal cancer, and HPV types 18 and 33 are classified as possible causes based on limited evidence.112 An estimated 90% of anal cancers in the UK are linked to HPV infection.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 and genetic syndromes

Familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC)

About 5% of bowel cancers are linked to FAP, HNPCC and the polyposis syndromes.115 Because FAP and HNPCC are relatively rare, they account for only small proportions of bowel cancer overall: FAP accounts for less than 1% of bowel cancers, and HNPCC for 1-4% of colon cancers.99,117 But almost all FAP patients develop bowel cancer by age 40,116 and around 9 in 10 males and 7 in 10 females with HNPCC develop bowel cancer by age 70.118

Other genetic syndromes

Around 20% of bowel cancers are associated with hereditary factors in the absence of FAP and HNPCC.115 Bowel cancer risk is around twice as high in people with a first-degree relative with the disease, compared to the general population, with an even greater risk if there are multiple or young affected relatives.119,120 Bowel adenoma risk is 70% higher in those with a first-degree family history of bowel cancer.121

Bowel cancer risk may also be slightly increased in those with a second-degree relative with bowel adenoma, a case-control study showed.128 BRCA1 mutations may account for some of this excess familial risk, particularly in younger women.153

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Height

For every 5cm increase in height, colon cancer risk is 11% higher in females and 9% higher in males, and rectum/anus cancer risk is 9% higher in females and 6% higher in males, a pooled analysis of Nordic data showed.143 The association with height was significant only for colon cancer, not rectal, in a US pooled cohort study.144

section reviewed 06/12/13
section updated 06/12/13

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