Alcohol consumption and risk of cancer in humans: An overview

Pergamon

Alcohol, Vol. 12, No. 2, pp. 87-%,1995 Copyright o 1995 Elsevier Science Ltd

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Alcohol Consumption and Risk of Cancer in Humans: An Overview’

MATTHEW P. LONGNECKER

Department of Epidemiology, UCLA School of Public Health, 10833 Le Conte Avenue, Los Angeles, CA 90024-I 772

Received 11 October 1994

LONGNECKER, M. IP. Alcohol consumption and risk ofcancer in humans: An overview. ALCOHOL 1x2) 87-%. 1995. - Recent epidemiologic data continue to support alcoholic beverage consumption as a cause of cancer of the mouth, pharynx, larynx, esophagus, and liver. The effect of a given alcohol intake on absolute risk of these cancers depends on the prevalence of other risk factors. Whether alcoholic beverage consumption is a cause of cancer of the breast or large bowel is unclear. Alcohol intake appears not to increase risk of cancer of the lung, bladder, prostate, stomach, ovary, endometrium, or of melanoma. Indirect epidemiologic evidence suggests that alcohol may be a weak causal factor for pancreatic cancer. Addi- tional research is needed to determine whether middle-aged women who drink moderately may experience. a slight increase in longevity if they decrease alcohol intake. A number of biologically plausible mechanisms exist by which alcohol may cause cancer.

Alcohol drinking Cancer Human

THE International Agency for Research on Cancer (IARC) (46). Among those who drink heavily, however, underestima- published a comprehensive, authoritative review of the data tion of intake is likely (100). Misreporting of alcohol intake on alcohol and cancer in 1988 (61). In this review we reexam- by heavy drinkers could artifactually increase or decrease the ine the IARC conclusions in light of more recent data from associations observed in epidemiologic studies (9), depending case-control studies, from cohort studies based on self- on how they classified themselves; conjecture as to the overall reported alcohol use, and from selected studies on the mecha- effect of this misclassification would be highly speculative. nisms of alcohol carcinogenesis. Where available, we make Because of the imprecision in measurement of dose among use of recent good quality reviews of data on specific cancer heavy drinkers, in this review we have not included informa- sites. tion from cohort studies of alcoholic populations.

This update review is org,anized as follows: a) we briefly consider measurement of akoholic beverage consumption in epidemiologic studies, b) for cancers caused by alcohol we review some details of the relation, c) we review the evidence on alcohol consumption in relation to cancer of the breast and large bowel, d) we briefly review epidemiologic evidence on the relation between alcohol consumption and other common cancers, e) we review some mechanisms proposed for alcohol’s role in carcinogenesis, and f) we briefly consider aspects of the public health implications of the findings.

Of note also is that measurement of alcohol intake in epidemiologic studies has-been of the average rate of consumption. Thus, distinguishing between the effects of steady drinking compared with binge drinking (after accounting for average dose) is not possible with the available data.

CANCERS CAUSED BY ALCOHOL

MEASUREMENT OF ALCOHOL CONSUMPTION IN EPIDEMIOLOGIC STUDIES

The validity of reported alcohol consumption among non- alcoholic populations has in general been shown to be high

IARC concluded that alcohol consumption causes cancer of the mouth, pharynx, larynx, esophagus, and liver in humans (61). The ratio of cancer risk in heavy drinkers compared with that in abstainers is greatest for cancers of the oral cavity, larynx, pharynx, and esophagus. The relative increase in risk of liver cancer is less pronounced (25,26,67). Whether a gradient in risk exists along the upper aerodigestive tract, with the effect of alcohol being greatest for cancer of the

’ Presented at the Symposium on Alcohol and Cancer, Research Society on Alcoholism, Kaanapali Reach, Maui, HI, June 19,1994.

87

88 LONGNECKER

TABLE 1 RELATIVE RISK (RR) OF ORAL CAVITY CANCER

AMONG NONSMOKING MALES IN THE US, ACCORDING TO LEVEL OF ALCOHOL INTAKE

Alcohol Intake @rinks/Day) RR 95% CI

0 1 <l 1.33 0.57-3.13

l-2.9 2.37 1.00-5.64 3-6.9 2.89 1.10-7.60 7+ 4.36 1.39-13.7

Based on data from 73 cases and 254 controls [adapted from Ng et al. (%)I. RR is adjusted for age and area. CI = confidence interval. One drink contains about 13 g of alcohol.

mouth and smallest in the esophagus, is not clear (25,26, 36,132).

Head and Neck Alcoholic beverage consumption causes cancers of the head

and neck in lifelong nonsmokers. Table 1 shows the results of a case-control study of oral cancer conducted among hospital- ized American males who never smoked (96); subjects who had seven or more drinks/day had a risk of cancer more than fourfold greater than abstainers. Also of note is the finding in humans that use of mouthwash containing 25% or more ethanol is associated with increased risk of cancer of the mouth (Table 2) (133). The proportion of all cancers of the head and neck attributable to the use of alcohol has been estimated to be 25-50’70 (36).

The absolute risk of cancer of the head and neck associated with a given level of alcohol consumption greatly increases with amount smoked. As an example of this, Fig. 1 shows the results of a large case-control study of alcohol, tobacco, and oropharyngeal cancer (11). Though much less strong than the tobacco effect, fruit and vegetable intake appears to modify the effect of alcohol much as tobacco does- with the absolute effect on risk of a given dose of alcohol being greater among those with smaller intakes of these foods (12,18). The protective effect of diet may be more than just prevention of carcinogenesis due to nutrient deficiency (43); fruits and vegetables

TABLE 2 RELATIVE RISK (RR) FOR ORAL CANCER

ASSOCIATED WITH MOUTHWASH USE IN FEMALES

Alcohol Content* RR 95% CI

None 1 Low 0.8 0.4-1.5 High 1.9 1.1-3.3 Mixed 2.0 1.3-3.1

Based on data from 293 cases and 428 controls [adapted from Winn et al. (133)]. RR is adjusted for age, race, education, smoking, drinking, and fruit intake. CI = confidence interval. *High alcohol content means 1 25% alcohol.

Drinking Effect Depends on Smoking Data for Oral and Pharyngeol Cancer

cigs/day

o- I

0 5 10 15 20 25 30

drinks/week

FIG. 1. Risk of cancer of the oropharynx in males, relative to nonsmoking teetotalers. Adapted from Blot et al. (11). Results based on 753 cases and 832 controls. Gigs/day, cigarettes/day. Relative risk adjusted for smoking, age, race, study location, and respondent status.

contain substances that may reduce risk of cancer in nutrition- ally replete individuals (10).

Esophagus

Alcoholic beverage consumption also causes esophageal cancer in nonsmokers (120,124) (Table 3). As with cancers of the head and neck, evidence of an alcohol effect on esophageal cancer in nonsmokers suggests that alcoholic beverages by themselves cause cancer in humans, and do not merely amplify an effect of smoking at these sites. Franceschi et al. (36) have estimated that 50% of all esophageal cancers are attributable to alcohol use.

For esophageal cancer the results of several studies suggest that consumption of a given amount of alcohol in distilled spirits results in a greater increase in risk than consumption of the same amount of alcohol in other beverages (19,21,124). Certain distilled spirits, such as moonshine and apple brandy, have been implicated more than others (19,124).

The absolute risk of cancer of the esophagus associated with a given level of alcohol consumption also greatly increases with amount smoked. As an example of this, Table 4 shows the results of a case-control study of alcohol, tobacco, and esophageal cancer (36). Low fruit and vegetable intake

TABLE 3 RELATIVE RISK (RR) OF CANCER OF THE ESOPHAGUS IN NONSMOKING ITALIANS

Alcohol Intake (Drinks/Day) RR 95% CI

<4 1 4-<8 2.7 1.1-6.8

>8 5.4 1.4-21.0

Based on data from 46 cases and 230 controls [adapted from Tavani et al. (120)]. RR is adjusted for age, sex, and education. CI = confidence interval. One drink contains about 13 g of alcohol.

ALCOHOL AND CANCER IN HUMANS 89

TABLE 4 RELATIVE RISK OF ESOPHAGEAL CANCER ACCORDING TO

A;;m@%i km;,ok@$e

LEVEL OF ALCOHOL INTAKE, BY AMOUNT SMOKED

Smoking Status

Alcohol Intake (Drinks/Day) Nonsmoker Light Med Heavy

C5 1 1.1 2.1 6.4 z X

5-8.4 0.8 7.9 8.8 11.0 1 m 3 X _ 8.5+ 7.9 9.4 16.7 17.5

Y

.- -

Data based on 288 Italian males with esophageal cancer and 1272 z o_* controls [adapted from Frances&i et al. (36)]. RR is adjusted for age, n -

1 - area, education, and occupation. One drink contains about 13 g of alcohol. 0

0 __I/

0 1 2 3 4 5 also appears to modestly increase the absolute risk of esophageal cancer in alcohol users (12,120).

Number of Alcoholic Beverages Consumed Doily

Liver

The effect of alcohol consumption on risk of cancer of the liver is subtle-enough so that occasionally studies show no effect of alcohol (1). Nonetheless, the vast majority of recent studies show that heavy drinking increases risk [e.g., see (24, 30,37,54,78,91,119,122,126,135)].

Viral hepatitis also increases risk of hepatoma (2437, 119,122), and when present together with heavy alcohol consumption the combination g,reatly increases the absolute risk of liver cancer (Table 5). Heavy alcohol consumption and viral hepatitis both increase the risk of cirrhosis, which in turn greatly increases the risk of hepatocellular carcinoma (1).

Whether alcohol increases risk of hepatocellular carcinoma solely by inducing cirrhosis is unclear. Adami et al. (1) and Hirayama (54) both present evidence suggesting that among cirrhotics alcohol consumption does not further increase risk of hepatoma. But not all aLlcoholics with liver cancer have cirrhosis (4); thus, more than one causal mechanism for alcohol may exist for cancer at this site.

ALCOHOL AND CANCER OF THE LARGE BOWEL

Evidence regarding alcohol as a cause of cancer of the large bowel was considered suggestive but inconclusive by IARC (61).

Figure 2 shows the results of a case-control study based on interviews with 393 men with cancer of the rectum and 992 controls (84). Heavy drinking was associated with a moderate

TABLE 5 RELATIVE RISK OF LIVER (CANCER ACCORDING TO LEVEL

OF ALCOHOL INTAKE, BY SEROLOGIC MARKER STATUS FOR HEPATITIS B

HBsAg HBeAg

Drank > IIDrinkdWeek for >lSYears

No Yes

N Drinking

Cases / Control

- 1.0 3.4 10 18 + 17.0 57.1 37 4 + + 55.6 151.6 12 0

Data from Taiwan [adapted from Chen et al. (ZS)]. HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen. Relative risk is adjusted for age, sex, Iethnicity, and residential area. One drink contains about 13 g of alcohol.

FIG. 2. Relative risk of cancer of the rectum in males according to number of alcoholic drinks consumed daily. Adapted from Long- necker (84). Results based on 393 cases and 992 controls. Relative risk is adjusted for age, income, and smoking (further adjustment for dietary factors had little effect).

increase in risk of rectal cancer. The association was slightly greater with beer consumption, but the data were not conclu- sive on this point. Similar findings were present for cancer of the colon. In this study, as in others with dietary data, the alcohol-large bowel cancer association was not attributable to the diet or other characteristics of drinkers.

Figure 3 shows the results of a meta-analysis of alcohol consumption and risk of large bowel cancer (83). This is the weighted average dose-response observed in 27 studies. On average, for each drink consumed daily, the risk of colorectal cancer increased by 5% -a weak association. Nonetheless, the data considered in aggregate were consistent and strongly supportive of a dose-response relation. Although the greater association of beer consumption with risk has been observed frequently, overall the evidence on this is inconclusive. Studies reported since the 1990 meta-analysis continue to support a

Alcohol and Large Bowel Cancer

1

drinks/day

FIG. 3. Relative risk of cancer of the large bowel according to number of alcoholic drinks consumed daily. Adapted from Longnecker (83). Results based on a meta-analysis of data from 27 studies.

90 LONGNECKER

Avera e Daily Alcohol Intake and # isk of Breast Cancer

xj ,OVD Women’s Health Study

0.0 0.4 0.6 1.2 1.6

Number of Alcoholic Eeveroges Consumed Doily

FIG. 4. Relative risk of cancer of the breast in women according to number of alcoholic beverages consumed daily. Adapted from Gap- stur et al. (41). Results based on 493 cases of breast cancer arising among 41,837 women followed for 4 years. Relative risk is adjusted for age, body mass index, age at menarche, age at first live birth, and family history of breast cancer. Further adjustment for dietary and other risk factors had no material effect on the results.

weak association of alcohol with risk of large bowel cancer (7,8,23,26,47,55,58,60,68,71,84,89,95,99,104,115,116).

When an association is weak, causality is difficult to estab- lish with nonexperimental data. In this case, evidence from other sources may influence assessment of causality. Animal models of the relation between alcohol and large bowel cancer have given inconsistent results (76). Human studies on the relation between colorectal polyps (a precursor to cancer) and alcohol consumption in general support an association (94).

In summary, strong epidemiologic evidence of a weak association between alcoholic beverage consumption and risk of large bowel cancer has been found rather consistently. Evi- dence that a given amount of alcohol consumed in beer is more strongly associated with risk than is consumption of that amount in other beverages is inconclusive. Overall the data regarding causality remain suggestive but inconclusive.

ALCOHOL AND CANCER OF THE BREAST

Evidence regarding alcohol as a cause of cancer of the breast was considered suggestive but inconclusive by IARC (61).

Gapstur and colleagues recently reported the results of a cohort study of 493 breast cancer cases that occurred among 41,837 women followed for 4 years (Fig. 4) (41). In women who drank on average more than one drink daily the risk of breast cancer increased by about 50%, after adjustment for potentially confounding factors. Gapstur et al.‘s result is fairly typical of the epidemiologic data available.

Figure 5 shows the results of a meta-analysis of studies on alcohol and breast cancer (85). This is the weighted average dose-response curve found in 38 studies. The results among studies varied markedly, though on average, for each drink consumed daily, risk increased by 10% -a very modest association. Nonetheless, the association is statistically significant. Studies from countries with higher per capita alcohol consumption tend to show slightly larger associations. No specific type of alcoholic beverage seems to be associated with risk

more than others. Adjustment of the association for the tradi- tional risk factors for breast cancer has little effect on the relation observed.

Although several plausible mechanisms exist by which alcoholic beverage consumption might increase risk of breast cancer, one leading hypothesis relates to the effect of alcohol consumption on hormone levels (see section on Mechanisms). A causal relation between hormone levels and risk of breast cancer, however, has not been proven, although it is suspected (73).

Many investigators have tried to develop animal models of alcohol-induced mammary carcinogenesis (108). Only two groups, however, have been successful (109,113). Evidence on whether alcohol is associated with benign breast disease, an established risk factor for breast cancer, is mixed (16,39,105).

In summary, the epidemiologic data on alcohol and breast cancer show strong evidence of a dose-response relation that is modest. The results vary widely from study to study. Plausi- ble causal mechanisms exist but the data are weak. Whether alcohol causes breast cancer is not known. Even if alcohol was causal, because in general women do not drink much, and because the effect on risk, if any, is subtle, only about 4% of all breast cancers would be attributable to alcohol consumption (85).

ALCOHOL AND OTHER CANCERS

For the cancers discussed below, evidence regarding alcohol as a cause was considered by IARC to be either insufficient for an assessment or not supportive of causality (61).

Pancreatic Cancer

The data on alcoholic beverage consumption and risk of pancreatic cancer are mixed (17,128). For example, among recent studies, although most studies show no association (15,22,28,35,45,63&j), some find alcohol to be a risk factor, even after adjusting for smoking (31,136,137). Alcohol consumption increases risk of pancreatitis (112), and pancreatitis increases risk of pancreatic cancer (86), thus it is plausible that

Alcohol and Breast Cancer

Data From 38 Studies

drinks/day

FIG. 5. Relative risk of breast cancer in women according to number of alcoholic beverages comnmmd daily. From Longnccker (85) 0 1994 Rapid Communications of Oxford, Ltd. reprinted with permission. Results based on a me&analysis of data from 38 studies.

ALCOHOL AND CANCE:R IN HUMANS 91

alcohol is causal. If alcohol consumption causes pancreatic cancer by this mechanism, the association is probably weak, and thus epidemiologic data cannot be expected to resolve the issue of causality.

Stomach Cancer

We identified 16 recent analytical studies (2,14,32,51,57, 62,64,65,69,70,75,80,98,121,134) not previously reviewed (13,61). Of these, only one small follow-up study (70), and two case-control studies (6480) support an association. In one of the positive case-control studies (64), done in Poland, the risk of stomach cancer was Iincreased even among those who consumed alcohol rarely, suggesting drinkers were at increased risk of stomach cancer for some reason other than alcohol consumption. In an earlier review, Boeing (13) found that the data in four cohort {studies consistently supported no association, and that data in case-control studies were mixed. IARC (61) reported “ . . . little in the aggregate data to suggest a causal role . . . ” Overall, of the more than 40 studies of alcohol and stomach cancer, only the occasional study is positive.

Lung Cancer

An increased risk of lung cancer among drinkers, even after adjusting for amount slmoked, has been reported in several recent studies (6,33,102). In these studies, however, the authors adjusted for pack-years smoked, but not recency of smoking, and risk of lung c,ancer is known to decrease after smoking cessation (27). The association of risk with alcohol use in these studies may merely reflect the current or more recent smoking among drinkers. In addition, even if the alcohol-lung cancer association persisted after adjusting for recency and pack-years of smoking, misclassification of smoking might cause a spurious alcohol-lung cancer relation (92). Thus, observational epidemiologic studies showing a positive association constitute weak evidence of causality. Further- more, in other studies, after adjustment for smoking, an alcohol-lung cancer association ‘was not evident (27,61). Overall, strong evidence to suggest au alcohol-lung cancer association is absent.

Bladder Cancer

In a recent review of data on alcohol and cancer of the bladder, Silverman et al. (110) concluded that most studies do not support an association. Among the few positive studies the findings were felt to be inconsistent across and even within studies.

Prostate Cancer

Nearly all available studies (52,59,61,90,106,114,116,129) support no association between alcohol and prostate cancer. The one positive study (53) was of Japanese males and control for potentially confounding factors was incomplete.

Ovarian Cancer

Ovarian cancer risk was significantly decreased among heavier drinkers in two (50,72) of the nine studies available (50,61,72,79,101,125,131). Tzonou et al. (125), on the other hand, found that risk of ovarian cancer increased with dura- tion of alcohol consumption. Overall the epidemiologic data

do not appear to support alcohol as a risk factor for ovarian cancer.

Endometriai Cancer

Endometrial cancer risk was decreased among heavier drinkers in five (5,72,118,130,132) of the seven available studies (5,42,72,77,118,130,132). Conversely, both La Vecchia et al. (77) and Gapstur et al. (42) found an increased risk among heavier drinkers. Swanson et al. (118) examined the association with alcohol separately for pre- and postmenopausal women and found a protective association only among premenopausal women. Overall the data suggest alcohol does not increase risk of endometrial cancer. Additional data are needed to see if alcohol decreases risk in premenopausal women.

Melanoma

Most studies of alcohol and melanoma show no association (40,48,56,74,132). One positive study (117) and one study with an inverse association (97), however, have been reported. On the whole, the data suggest no association between alcohol and melanoma risk.

Other Common Cancers

Alcohol consumption does not appear to increase risk of kidney cancer; in fact, some evidence suggests intake reduces risk (88). Kato et al. (67) found an association between alcohol intake and risk of leukemia and lymphoma, but a subsequent larger study (20) did not support this finding.

MECHANISMS OF ALCOHOL IN CARCINOCENESIS

The exact mechanisms by which alcohol causes cancer in humans have not yet been determined, though many hypotheses exist (Table 6) (12,43). In animal models alcohol does not initi- ate cancer (43,61). In these models, however, alcohol can increase the effect of substances that are carcinogenic. In this section we will review evidence regarding selected mechanisms by which alcoholic beverage consumption might either directly affect cancer risk, or affect intermediate steps in carcinogenesis.

Some compounds besides ethanol in alcoholic beverages are carcinogenic. For example, the content in beverages of ethyl carbamate, a carcinogen in animals, is now being re-

TABLE 6 PROPOSED CARCINOGENIC MECHANISMS

FOR ALCOHOL OR ALCOHOLIC BEVERAGES*

1. Congenas 2. Acetaldehyde 3. Solvent 4. Displace nutrients in diet 5. Impair nutrient metabolism 6. Inhibit detoxification 7. Activate enzymes 8. Alter hormonal status 9. Increase oxidant exposure

10. Suppress immune function 11. Alter membrane fluidity 12. Increase cellular proliferation

*Adapted from Blot et al. (12).

92 LONGNFKXER

duced by beverage producers in the US and Canada (34). As noted previously, alcohol consumed in distilled spirits is some- times more strongly associated with risk of esophageal cancer than is consumption of an equivalent amount of alcohol in other alcoholic beverages (19,21,124). Although this finding is interpreted by some (12) as suggestive of substances other than alcohol in distilled spirits adding to the effect of alcohol, it may also suggest that alcohol, consumed in a concentrated form, has an increased carcinogenic effect on the esophagus, and possibly at other sites.

Acetaldehyde, a product of alcohol metabolism, is a carcinogen in animal models (61). After alcohol consumption, acetaldehyde was detected in the serum of Finnish women (38), raising the possibility that alcohol via acetaldehyde may increase risk of cancers both within and outside the liver.

Some carcinogens, when given in an alcohol solution, have greater effect in animals (61 : 113; 61 : 252)-possibly due to a solvent effect of alcohol. The finding in humans that use of mouthwash containing 25% or more ethanol is associated with increased risk of cancer of the mouth (Table 2) (133) is consistent with the solvent hypothesis.

Among malnourished alcoholics the lower intake of fruits and vegetables may augment the effect of alcohol on risk of cancers of the head, neck, and esophagus (43). In many studies of nonalcoholics, however, the most common difference between the diet of drinkers and nondrinkers is that drinkers consume less carbohydrate (29), a difference that probably has little, if any, effect on cancer risk.

Alcohol consumption is also known to decrease the amount of vitamin A stored in the liver (81). Vitamin A is known to be important in controlling cell differentiation, a key process in carcinogenesis.

In animal models, alcohol has been shown to decrease ex- pression of detoxifying cytochrome P450 enzymes in the liver (127). Thus, some carcinogens may be metabolized more slowly in drinkers. Furthermore, CYP2El , a cytochrome oxi- dase that converts ethanol to acetaldehyde, also metabolizes a procarcinogen, N-nitrosodimethylamine (NDMA) to its active form (NDMA is present in tobacco smoke and foods). When alcohol and NDMA are given to animals concurrently, the metabolism of NDMA is inhibited, and the carcinogenic effect of a given dose of NDMA is greater-presumably due to its longer half-life (3).

Conversely, because CYP2El is induced by alcohol consumption (123), metabolism of NDMA between episodes of alcohol consumption may be more efficient, which may have additional implications for alcohol’s effect.

Alcohol consumption may increase the levels of estrogens and alter other hormones levels in humans; these mechanisms have recently been discussed in detail elsewhere (44,82,108).

In animal models, alcohol increased the rate of epithelial proliferation in the rat rectum (111) and increased the rate of proliferation of rat mammary terminal end buds (113). With increased cellular turnover the risk of neoplasia is greater (103).

SHOULD WOMEN WHO DRINK MODERATELY CONTINUE TO DO SO?

The U-shaped relation between alcohol consumption and total mortality rate is fairly well established (49). Thus, if a woman drinks heavily this is clearly detrimental, because of the relation of heavy consumption with increased total mortality (49). Moderate alcohol consumption is, however, associated with a slightly lower risk of death compared with abstaln- ers, because of the beneficial effects on risk of coronary heart

disease (CHD) (87). Calculation of total mortality rates in studies of the type cited above, however, are based on the weighted average of death rates in all age groups, and are affected greatly by disease patterns in the elderly. Among the elderly, CHD is the leading cause of death (93). For middle-aged women (< 55 years old), however, breast cancer is a more frequent cause of death than is CHD (93). Thus, the possibility exists that for middle-aged women who drink moderately, decreasing alcohol consumption may increase lifespan.

Let us consider further whether a middle-aged woman who drinks moderately might increase longevity from decreasing alcohol consumption. First, the benefit, if any, would be due primarily to decreased risk of breast cancer (assuming a causal relation), which is by far the most frequent of cancers among females in this age group. Breast cancer, however, accounts for only 12% of deaths in the 50-54 age group. Thus, an intervention that would change breast cancer mortality would have only a subtle effect on total mortality. Second, the small decrease in risk of breast cancer mortality (if any) would be partially offset by a small increase in risk of CHD [the effect of one drink alcohol daily on risk of each of these diseases is roughly on the same order of magnitude, i.e., about 10% (85,87)]. Third, assuming that alcohol is causal, for a benefit to occur the effect of alcohol on risk of breast cancer must have a short latency (i.e., within 10 years). This assumption is reasonable (unpublished data, Longnecker, 1994). Overall, then, for a middle-aged woman, a benefit of decreasing alcohol consumption on longevity is plausible, but likely to be of subtle magnitude. The potential benefit may be slightly greater for a subgroup of women at low risk of heart disease or high risk of breast cancer. A formal risk-benefit analysis, or de- tailed analysis of epidemiologic data on alcohol and mortality in middle-aged women, is needed to assess the size of the potential benefit, if any.

CONCLUSION

On the basis of alcohol’s effect on cancer of the head, neck, esophagus, and liver, Rothman et al. concluded that about 3% of all cancers in the US were attributable to alcohol consumption (107).

Data published since the IARC review (61) confirm the findings of that group, and allow better assessment of the association of cancer risk with alcohol, especially for some of the less common cancers (e.g., endometrium, melanoma). The effect of a given leve1 of alcohol intake on absolute risk of cancers of the head, neck, and esophagus depends on the level of smoking and amount of fruit and vegetables consumed. Likewise, the effect on absolute risk of liver cancer depends on whether hepatitis is present. Additional mechanistic evidence may increase understanding of how alcohol causes cancer and whether alcohol causes cancer of the large bowel and breast. The epidemiologic data suggest alcohol consumption does not increase risk of melanoma or of cancers of the lung, bladder, prostate, stomach, ovary, and endometrium. Direct epidemiologic evidence that alcohol causes pancreatic cancer is not strong. Indirect epidemiologic evidence, however, suggests that alcohol may be a weak causal factor for this disease. Additional research is needed to determine whether middle- aged women who drink moderately may experience a slight increase in longevity if they decrease alcohol intake.

ACKNOWLEDGEMENT

The author is grateful to Dr. Thomas Mack for his comments on an early draft of this manuscript.


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Alcohol consumption and risk of cancer in humans: An overview