- Email: [email protected]
Moderate Alcohol Consumption and Cancer
Moderate Alcohol Consumption and Cancer KLIM MCPHERSON, PHD, FFPH, FMEDSCI
Alcohol consumption may increase the risk for at least six types of cancer, although the evidence is not uniformly strong. Alcohol is not a carcinogen in standard tests but is likely a cocarcinogen, at least in the digestive tract. The strongest association is with cancer of the oral cavity and pharynx (seven-fold increase for heavy consumption). For moderate consumption (2–3 drinks/day for men and 1–2 drinks/day for women), the risks never increase above twofold and are mostly less than 25% above baseline. The evidence from the epidemiological literature suggests that 25g/d of alcohol is associated with a relative risk of 1.9 for cancers of the oral cavity and pharynx, 1.4 for cancers of the esophagus and larynx, about 10% for colorectal cancer (mechanisms unclear), and 20% for liver cancer (mechanisms well described). The association between alcohol and breast cancer is not strong and not necessarily causative, at least for moderate consumption. In the United Kingdom, cancer deaths attributable to alcohol consumption above the recommended limits (caused mostly by colorectal cancer) are maximal for men aged 65 to 74 years and for women at ages 75 to 84 years. It is postulated that if everyone in the United Kingdom drank ‘‘sensibly,’’ there would be a marked increase in cancer deaths. Ann Epidemiol 2007;17:S46–S48. Ó 2007 Elsevier Inc. All rights reserved. KEY WORDS:
Alcohol Drinking, Cancer, Epidemiology.
Total alcohol consumption worldwide, including heavy drinking, is responsible for only 5.2% of cancers in men and 1.7% among women (1). Since the risk relationships between alcohol consumption and cancer are dose dependent, this suggests that moderate drinking increases the risk for only a small proportion of all cancers. In public health terms, this relationship is of minor significance. A recent meta-analysis of the relationships between alcohol consumption and disease has reviewed 156 studies involving 117,000 subjects (2). The findings on the incidence of cancer suggest a strong relationship with cancers of the oral cavity, pharynx, esophagus, and larynx. The observed magnitude of the association with cancers of the colon, rectum, liver, and breast is weaker. The summary relative risks are shown in Table 1. The strongest relative risk is mostly seen for the rarest cancers. Of the more common cancers (Fig. 1), namely, cancers of the colon, breast, liver, and esophagus, the relationship with moderate alcohol consumption is weaker overall and hence less likely to be causal. Ethanol is not a carcinogen by standard laboratory tests. However, it may act as a cocarcinogen in the esophagus and nonglandular parts of the stomach, as determined by animal experiments. The mechanisms underlying the association with colon cancer and breast cancer remain unclear and
From the University of Oxford, United Kingdom. Address correspondence to: Klim McPherson, The John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. Tel: þ44 1865 221 021. E-mail: [email protected]. Ó 2007 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010
thus for such moderate associations need not be causal. Risk for both colon and rectal cancer is similar for men and women. Whether these associations are a manifestation of confounding with some dietary factor, smoking, other substance misuse, or publication bias remains unresolved. However, all are clearly plausible explanations. The evidence on the relationship of alcohol with cancer of stomach or pancreas suggests no link (3). The relationship between alcohol and the risk for breast cancer remains ambiguous. Epidemiological studies suggest an association between increased risk and heavy drinking, although results are not consistent. In these cases, the association is more likely to be accounted for through unknown confounders and publication bias than to be causative. However, some have argued strongly for a causal link. To date, no evidence can usefully distinguish between the two explanations (4, 5). Assuming a causal relationship, Boffetta et al. (1) estimate that 60% of alcohol-attributable cancers in females are due to breast cancer. However, this may be an artefact. Calculations of the effect of alcohol consumption on cancer generally assume the relative risks to be causal. Thus these estimates are likely to exaggerate the true effect of alcohol on cancer among populations. Clearly some of the epidemiological evidence indicates a causal relationship between alcohol intake and the risk of cancer, particularly of the upper digestive tract for which the risk relationship with consumption is strong. It is therefore interesting to ask questions about not only how much cancer may be caused by alcohol, but also how much may be preventable by changes in alcohol consumption. 1047-2797/07/$–see front matter doi:10.1016/j.annepidem.2007.01.011
AEP Vol. 17, No. 5S May 2007: S46–S48
McPherson ALCOHOL CONSUMPTION AND CANCER
S47
TABLE 1. Relative risks (and 95% confidence intervals) of various cancer sites associated with alcohol consumption* Alcohol consumption Cancer site
Studies (No.)
Cases (No.)
25 g/d
50 g/d
100 g/d
15 20 14 24 8 4 12
507 3789 3233 32175 1321 1420 5360
1.86 (1.76–1.96) 1.43 (1.38–1.48) 1.39 (1.36–1.42) 1.25 (1.2–1.29) 1.19 (1.12–1.27) 1.09 (1.08–1.12) 1.05 (1.01–1.09)
3.11 (2.85–3.39) 2.02 (1.89–2.16) 1.93 (1.85–2.00) 1.55 (1.44–1.67) 1.40 (1.25–1.56) 1.19 (1.14–1.24) 1.10 (1.03–1.18)
6.54 (5.76–7.24) 3.86 (3.42–4.35) 3.59 (3.34–3.85) 2.41 (2.07–2.80) 1.81 (1.5–2.19) 1.42 (1.3–1.55) 1.21 (1.05–1.39)
Oral cavity and pharynx Larynx Esophagus Breast Liver Rectum Colon *From Corrao et al. (2).
Calculations of attributable fractions have examined by how much cancer incidence (or mortality) would be reduced if alcohol were not consumed at alldan unlikely prospect. It is more interesting to examine what might happen if heavy drinkers reduced their consumption to sensible levelsd probably an equally unlikely prospect. In the United Kingdom, sensible drinking is defined as 3 to 4 drinks a day for men or 2 to 3 for women, where a drink is assumed to contain 8 g of ethanol. This will enable some estimate of the contribution of sensible drinking to cancer, assuming that the estimated risks represent a causative relationship. Indeed, one might speculate what might happen if everyone, even current abstainers, drank so-called ‘‘sensible’’ amounts. Fig. 2 shows the effect these strategies could have on cancer deaths. This analysis shows that, since women drink less than men, the effect of heavy-drinking women changing to
moderate drinking is minimaldeven for breast cancer. For men, the effect is also small, reflecting the proportion of the population who drink more than the recommended limits. On the other hand, were both women and men to drink ‘‘sensibly,’’ then cancer deaths would increase dramatically.
CONCLUSIONS Moderate alcohol consumption as currently consumed has a small effect on the incidence of cancer. However, its importance for increased incidence were populations to drink more overall should not be ignored. The mechanisms by which alcohol might induce common cancers require more rigorous research. Merely repeating findings from
Effects on cancer deaths on changing drinking patterns
% Cancer incidence by site and sex 1800 70
Males Females
Adult Deaths in E&W
60 50
%
1600
40 30 20
1400 1200 1000 800 600 400
ec
Female
Male
Female
Male
Female
on
Male
Current
Heavy - Sensible
All - Sensible
R
C ol
r ve Li
st ea
O
es
op
Br
ou ha g
ry n La
tu m
0 s
0 x
200
an ra d lc ph a ar vit yn y x
10
O
Colon Liver Oesophagous Breast
Site
FIGURE 1. Proportion of cancer incidence by site and by sex.
FIGURE 2. Estimated cancer deaths in the UK by sex attributable to current drinking patterns (left columns); all heavy drinkers drinking moderately (middle columns); and everyone, including abstainers, drinking moderately (right columns).
S48
McPherson ALCOHOL CONSUMPTION AND CANCER
observational epidemiological studies is unlikely to enhance our understanding, particularly as positive findings have a greater chance of publication. The disparity of the scientific effort dedicated to investigating the causative nature of the apparent protection of moderate alcohol against coronary heart disease compared with investigating the apparent raised risk of breast cancer seems completely misplaced. The latter is assumed to be causal, while the former is contested vigorously. On the whole, the breast cancer association seems to be accepted without serious criticism and yet the public health implications, where a lack of causality has been demonstrated, are quite as profound.
AEP Vol. 17, No. 5S May 2007: S46–S48
REFERENCES 1. Boffetta P, Hashiba M, La Vecchia C, Zatonski W, Rehm J. The burden of cancer attributable to alcohol drinking. Int J Cancer. 2006;119:884–887. 2. Corrao G, Bagnardi V, Zambon A, La Vecchia C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Prev Med. 2004;38:613–619. 3. Doll R, Forman D, La Vecchia C, Woutersen R., Alcoholic beverages and cancer of the digestive tract and larynx. In: Macdonald I, ed. Health issues related to alcohol consumption: ILSI, 1999. 4. McPherson K. Alcohol and breast cancer. Eur J Cancer. 1998;34:1307– 1308. 5. McPherson K, Cavallo F, Rubin E. Health issues related to alcohol consumption. In: Macdonald I, ed. Alcohol and breast cancer. Malden (MA): Blackwell Science; 1999:217–242.
Alcohol consumption may increase the risk for at least six types of cancer, although the evidence is not uniformly strong. Alcohol is not a carcinogen in standard tests but is likely a cocarcinogen, at least in the digestive tract. The strongest association is with cancer of the oral cavity and pharynx (seven-fold increase for heavy consumption). For moderate consumption (2–3 drinks/day for men and 1–2 drinks/day for women), the risks never increase above twofold and are mostly less than 25% above baseline. The evidence from the epidemiological literature suggests that 25g/d of alcohol is associated with a relative risk of 1.9 for cancers of the oral cavity and pharynx, 1.4 for cancers of the esophagus and larynx, about 10% for colorectal cancer (mechanisms unclear), and 20% for liver cancer (mechanisms well described). The association between alcohol and breast cancer is not strong and not necessarily causative, at least for moderate consumption. In the United Kingdom, cancer deaths attributable to alcohol consumption above the recommended limits (caused mostly by colorectal cancer) are maximal for men aged 65 to 74 years and for women at ages 75 to 84 years. It is postulated that if everyone in the United Kingdom drank ‘‘sensibly,’’ there would be a marked increase in cancer deaths. Ann Epidemiol 2007;17:S46–S48. Ó 2007 Elsevier Inc. All rights reserved. KEY WORDS:
Alcohol Drinking, Cancer, Epidemiology.
Total alcohol consumption worldwide, including heavy drinking, is responsible for only 5.2% of cancers in men and 1.7% among women (1). Since the risk relationships between alcohol consumption and cancer are dose dependent, this suggests that moderate drinking increases the risk for only a small proportion of all cancers. In public health terms, this relationship is of minor significance. A recent meta-analysis of the relationships between alcohol consumption and disease has reviewed 156 studies involving 117,000 subjects (2). The findings on the incidence of cancer suggest a strong relationship with cancers of the oral cavity, pharynx, esophagus, and larynx. The observed magnitude of the association with cancers of the colon, rectum, liver, and breast is weaker. The summary relative risks are shown in Table 1. The strongest relative risk is mostly seen for the rarest cancers. Of the more common cancers (Fig. 1), namely, cancers of the colon, breast, liver, and esophagus, the relationship with moderate alcohol consumption is weaker overall and hence less likely to be causal. Ethanol is not a carcinogen by standard laboratory tests. However, it may act as a cocarcinogen in the esophagus and nonglandular parts of the stomach, as determined by animal experiments. The mechanisms underlying the association with colon cancer and breast cancer remain unclear and
From the University of Oxford, United Kingdom. Address correspondence to: Klim McPherson, The John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. Tel: þ44 1865 221 021. E-mail: [email protected]. Ó 2007 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010
thus for such moderate associations need not be causal. Risk for both colon and rectal cancer is similar for men and women. Whether these associations are a manifestation of confounding with some dietary factor, smoking, other substance misuse, or publication bias remains unresolved. However, all are clearly plausible explanations. The evidence on the relationship of alcohol with cancer of stomach or pancreas suggests no link (3). The relationship between alcohol and the risk for breast cancer remains ambiguous. Epidemiological studies suggest an association between increased risk and heavy drinking, although results are not consistent. In these cases, the association is more likely to be accounted for through unknown confounders and publication bias than to be causative. However, some have argued strongly for a causal link. To date, no evidence can usefully distinguish between the two explanations (4, 5). Assuming a causal relationship, Boffetta et al. (1) estimate that 60% of alcohol-attributable cancers in females are due to breast cancer. However, this may be an artefact. Calculations of the effect of alcohol consumption on cancer generally assume the relative risks to be causal. Thus these estimates are likely to exaggerate the true effect of alcohol on cancer among populations. Clearly some of the epidemiological evidence indicates a causal relationship between alcohol intake and the risk of cancer, particularly of the upper digestive tract for which the risk relationship with consumption is strong. It is therefore interesting to ask questions about not only how much cancer may be caused by alcohol, but also how much may be preventable by changes in alcohol consumption. 1047-2797/07/$–see front matter doi:10.1016/j.annepidem.2007.01.011
AEP Vol. 17, No. 5S May 2007: S46–S48
McPherson ALCOHOL CONSUMPTION AND CANCER
S47
TABLE 1. Relative risks (and 95% confidence intervals) of various cancer sites associated with alcohol consumption* Alcohol consumption Cancer site
Studies (No.)
Cases (No.)
25 g/d
50 g/d
100 g/d
15 20 14 24 8 4 12
507 3789 3233 32175 1321 1420 5360
1.86 (1.76–1.96) 1.43 (1.38–1.48) 1.39 (1.36–1.42) 1.25 (1.2–1.29) 1.19 (1.12–1.27) 1.09 (1.08–1.12) 1.05 (1.01–1.09)
3.11 (2.85–3.39) 2.02 (1.89–2.16) 1.93 (1.85–2.00) 1.55 (1.44–1.67) 1.40 (1.25–1.56) 1.19 (1.14–1.24) 1.10 (1.03–1.18)
6.54 (5.76–7.24) 3.86 (3.42–4.35) 3.59 (3.34–3.85) 2.41 (2.07–2.80) 1.81 (1.5–2.19) 1.42 (1.3–1.55) 1.21 (1.05–1.39)
Oral cavity and pharynx Larynx Esophagus Breast Liver Rectum Colon *From Corrao et al. (2).
Calculations of attributable fractions have examined by how much cancer incidence (or mortality) would be reduced if alcohol were not consumed at alldan unlikely prospect. It is more interesting to examine what might happen if heavy drinkers reduced their consumption to sensible levelsd probably an equally unlikely prospect. In the United Kingdom, sensible drinking is defined as 3 to 4 drinks a day for men or 2 to 3 for women, where a drink is assumed to contain 8 g of ethanol. This will enable some estimate of the contribution of sensible drinking to cancer, assuming that the estimated risks represent a causative relationship. Indeed, one might speculate what might happen if everyone, even current abstainers, drank so-called ‘‘sensible’’ amounts. Fig. 2 shows the effect these strategies could have on cancer deaths. This analysis shows that, since women drink less than men, the effect of heavy-drinking women changing to
moderate drinking is minimaldeven for breast cancer. For men, the effect is also small, reflecting the proportion of the population who drink more than the recommended limits. On the other hand, were both women and men to drink ‘‘sensibly,’’ then cancer deaths would increase dramatically.
CONCLUSIONS Moderate alcohol consumption as currently consumed has a small effect on the incidence of cancer. However, its importance for increased incidence were populations to drink more overall should not be ignored. The mechanisms by which alcohol might induce common cancers require more rigorous research. Merely repeating findings from
Effects on cancer deaths on changing drinking patterns
% Cancer incidence by site and sex 1800 70
Males Females
Adult Deaths in E&W
60 50
%
1600
40 30 20
1400 1200 1000 800 600 400
ec
Female
Male
Female
Male
Female
on
Male
Current
Heavy - Sensible
All - Sensible
R
C ol
r ve Li
st ea
O
es
op
Br
ou ha g
ry n La
tu m
0 s
0 x
200
an ra d lc ph a ar vit yn y x
10
O
Colon Liver Oesophagous Breast
Site
FIGURE 1. Proportion of cancer incidence by site and by sex.
FIGURE 2. Estimated cancer deaths in the UK by sex attributable to current drinking patterns (left columns); all heavy drinkers drinking moderately (middle columns); and everyone, including abstainers, drinking moderately (right columns).
S48
McPherson ALCOHOL CONSUMPTION AND CANCER
observational epidemiological studies is unlikely to enhance our understanding, particularly as positive findings have a greater chance of publication. The disparity of the scientific effort dedicated to investigating the causative nature of the apparent protection of moderate alcohol against coronary heart disease compared with investigating the apparent raised risk of breast cancer seems completely misplaced. The latter is assumed to be causal, while the former is contested vigorously. On the whole, the breast cancer association seems to be accepted without serious criticism and yet the public health implications, where a lack of causality has been demonstrated, are quite as profound.
AEP Vol. 17, No. 5S May 2007: S46–S48
REFERENCES 1. Boffetta P, Hashiba M, La Vecchia C, Zatonski W, Rehm J. The burden of cancer attributable to alcohol drinking. Int J Cancer. 2006;119:884–887. 2. Corrao G, Bagnardi V, Zambon A, La Vecchia C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Prev Med. 2004;38:613–619. 3. Doll R, Forman D, La Vecchia C, Woutersen R., Alcoholic beverages and cancer of the digestive tract and larynx. In: Macdonald I, ed. Health issues related to alcohol consumption: ILSI, 1999. 4. McPherson K. Alcohol and breast cancer. Eur J Cancer. 1998;34:1307– 1308. 5. McPherson K, Cavallo F, Rubin E. Health issues related to alcohol consumption. In: Macdonald I, ed. Alcohol and breast cancer. Malden (MA): Blackwell Science; 1999:217–242.