Laryngeal cancer risk factors
This page presents information on the risk factors for laryngeal cancer, including tobacco and alcohol, diet, infections, medical conditions and previous cancers, family history and occupational exposures and indoor air pollution. A study published in December 2011 estimated that, in the UK, more than 90% of laryngeal cancers are linked to lifestyle and environmental factors.61
A study published in December 2011 estimated that around 79% of laryngeal cancers in the UK in 2010 were caused by smoking, and 25% were linked to alcohol.62,63 The combined effect of smoking and alcohol consumption has been estimated to account for 89% of laryngeal cancers in an international analysis.2
Smoking has a stronger effect than alcohol on risk of laryngeal cancer. The odds ratios for current smokers range widely from about three to 20, and there are significant trends of increasing risk with longer duration or greater intensity of smoking.1,3-5 A meta-analysis found a relative risk of laryngeal cancer for current smokers of seven, based on 10 studies, which was the highest of any of the types apart from lung.6 Cigar smoking has been associated with a 10-fold increased risk of laryngeal cancer,7 and pipe smoking with a six–10-fold risk increase of cancer of the larynx and hypopharynx combined.5
Studies show a clear trend of reducing risk of laryngeal cancer in past smokers compared to current smokers, although the number of years of quitting needed to have a significant reduction in risk compared with current smokers range from six–nine to 20 or more.1,3,4,8-10 A recent study showed that people who stopped smoking before the age of 35 or 20 or more years ago did not have a significantly higher risk than never smokers.11
A meta-analysis found a risk ratio for drinking 100 grams/day of ethanol of about four, after adjustment for smoking, and a risk ratio of 1.4 for people drinking 25 grams/day.12 The European Prospective Investigation into Cancer and Nutrition reported risk ratios for a 10 grams/day alcohol intake of 1.1 for men and 1.4 for women.13 The UK Million Women Study reported a similar risk increase for this level of consumption.14 Pooled analyses have reported a risk increase of about three in non-smokers drinking at least three–five drinks a day versus never drinkers.2,15 There is evidence that the risk of smoking and drinking combined may be as high as the two separate risks multiplied together and certainly greater than additive, with a 35-fold risk increase shown in a meta-analysis for people in the highest category of smoking and drinking.16
Tobacco and alcohol risk by sub-site
Some studies show that risks associated with smoking are twice as high or more for tumours of the supraglottis than glottis,9,17,18 although a further study has not replicated these findings.3 For alcohol consumption, risk ratios are slightly higher for the supraglottis than glottis in at least three studies9,17,19 although at least one study shows similar risks for the two subsites,3 and another study showed a greater effect of alcohol on the glottis.18
Environmental tobacco smoke and smokeless tobacco
Risk of laryngeal cancer has been shown to be higher in people who have never smoked but are exposed to environmental tobacco smoke (ETS) over a number of years, with risk ratios of almost 3 and 2 shown for exposures of more than 15 years at home or at work, respectively.20 An additional study showed a borderline significant risk increase with exposure to ETS from a spouse over a number of years of 20%.21 However, another recent study did not show a significant risk increase with exposure to ETS.5 The International Agency for Research on Cancer says there is limited evidence that ETS causes cancer of the larynx.22
No risk increase of laryngeal cancer was shown in a recent study of smokeless tobacco use in India.23 However, a study in Taiwan, showed a higher risk of laryngeal cancer in people using chewing tobacco, smoking and consuming alcohol, than in people only smoking and consuming alcohol.24
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Case-control studies have shown up to an 80% reduced risk in people with the highest intakes of fruit and vegetables,25-27 or fruit and vegetable fibre.28 In addition, eating a greater diversity of fruits and vegetables has been shown to reduce the risk.29 A 2003 meta-analysis of case-control studies showed a 27% reduction in risk for a 100g/day intake of fruit.30 However, the only cohort study carried out to date did not show a significant effect of fruit or vegetable intake on laryngeal cancer risk.31
Effects may vary by subsite, with a case-control study of dietary patterns in Uruguay showing a 25% reduced risk of tumours of the supraglottis in people with a dietary pattern characterised by high intakes of fruit, vegetables and fish, but no effect on risk of tumours of the glottis.32
One study has shown a reduced risk of laryngeal cancer in people with high levels of flavonoids in their diet, but given that major sources of the specific flavonoids are fruit and vegetables, the effects are difficult to separate out.33
A study published in December 2011 estimated that around 45% of cancers of the larynx in the UK in 2010 were linked to people eating fewer than five portions a day (400g/day) of fruit and vegetables.64 However, there is greater uncertainty around the link between diet and laryngeal cancer than there is for other factors, such as smoking and alcohol.61,64
A high intake of red and processed meat has been associated with an increased risk of laryngeal cancer in case-control studies. In one study, risk for people eating processed meat three or more times a week versus less than once a week was increased three-fold.34 In another study, there was a smaller risk increase of about two for people in the top quintile of processed meat consumption, and a risk increase of three for people eating the most red meat.25 A large study in Uruguay showed an increased risk with higher processed meat intake only (not red or total meat).35 A dietary patterns analysis found people with a strongly western-style diet, characterised by high intake of fried, barbecued and processed meat, had an odds ratio of three.32 Higher intake of total fat or cholesterol has been linked in a case-control study to an increased risk of laryngeal cancer, which may explain the association with red meat36,37 and with fried food.38
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Gastro-oesophageal reflux disease
A recent meta-analysis concluded that a diagnosis of gastro-oesophageal reflux disease increases risk of laryngeal cancer by two–three times.39
A meta-analysis reported an almost three-fold increased risk of laryngeal cancer in people with HIV/AIDS and a two-fold risk increase in transplant recipients, suggesting a role of immunosuppression in the disease.40
Human papillomavirus/helicobacter pylori
An increased risk of laryngeal cancer has been shown for people with evidence of human papillomavirus-16 (HPV-16)infection in the larynx (up to 19-fold risk increase), or in blood samples (up to a three-fold risk increase).41,42 It has been estimated that more than 10% of laryngeal cancers in the UK are linked to HPV infection.65 A meta-analysis showed a doubling in risk of laryngeal cancer in people infected with helicobacter pylori.43
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A six-fold increased risk of laryngeal cancer has been shown for people with a previous head and neck cancer.44
Laryngeal cancer risk is higher in male survivors of head and neck, oesophagus, lung and bladder cancers, with no association with previous cancer in females, a cohort study in France showed.67
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A pooled analysis of case-control studies showed a doubling in risk of laryngeal cancer in individuals with a history of head and neck cancer in first-degree relatives, after adjusting for the main lifestyle risk factors for laryngeal cancer.45 A 30% risk increase has been shown for people with a first-degree family history of non-head and neck smoking-related cancers.45
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Larynx is not one of the cancer types strongly linked with occupation. Some exposures in the workplace may make a small contribution to risk, although evidence in many cases remains conflicting.
Occupational exposure to coal dust has been shown in one study to increase laryngeal cancer risk, with a risk ratio of more than six for the most highly exposed.46 More than 50 years of exposure to coal as a fuel source in the home has been associated with a 3.6-fold increased risk.47 A 1999 meta-analysis of asbestos-exposed cohorts showed a 33–57% increased risk of laryngeal cancer, although there was no dose-response effect.48 Two subsequent studies also showed an increased risk.49,50 However, two other studies subsequent to the meta-analysis did not.51,52 It has been estimated that around 3% of laryngeal cancers in the UK are linked to occupational exposure to asbestos or sulphuric acid - that is around 60 cases in 2010.60, 66 Some studies show an increased risk of laryngeal cancer in relation to occupational exposure to wood dust,50,53-55 although others do not.49,56-59
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