Alcohol and Cancer - A summary of the clinical evidence

healthy living

Risk explained

Relative risk

Relative risk is the number that tells you how much changing something can change your risk compared to your risk of not doing anything at all. It is expressed as a percentage decrease or increase. If something you do or take doesn't change your risk, then the relative risk reduction is 0% (no difference). If something you do or take lowers your risk by 50% compared to someone who doesn't do the same, then that action reduces your relative risk by 50%. If something you do doubles your risk, then your relative risk increases 200%.

Absolute risk 

Absolute risk is the size of your own risk. Absolute risk reduction is the number of percentage points your own risk goes down if you do something protective, such as losing weight. The size of your absolute risk reduction depends on what your risk is to begin with.

Hazard Ratios

A hazard ratio considers your absolute risk to be 1. If something you do or take doesn't change your risk, then the hazard ratio is 1. If something you do or take lowers your risk by 25% compared to someone who doesn’t take the same step, then that action makes your hazard ratio 0.75, which means that the risk is 75% of what it was without taking the step (so your risk is 25% lower). If something you do doubles your risk, then your hazard ratio is 2.0.

Intrinsic and Extrinsic risk of developing cancer

A study published in Nature January 2016, "Substantial contribution of extrinsic risk factors to cancer development" by Song Wu et al appeared to confirmed that many cancers are caused by so called extrinsic or environmental factors. 

External factors like smoking, diet, sun, HPV (Human Papilloma Virus) and exposure to toxic chemicals cause more cancer than intrinsic factors like random cell mutations. Intrinsic factors accounted for just 10% to 30% of people’s lifetime risk of getting cancer, whilst extrinsic risks accounted for 70% to 90% for most common cancer types. 

The results are at odds with the results of a study in January 2015 published in Science which found that cell division and random mutations in DNA play the major role in the development of cancer.  "Variation in cancer risk among tissues can be explained by the number of stem cell divisions", Cristian Tomasetti. They concluded that "Why do some tissues give rise to cancer in humans a million times more frequently than others? Tomasetti and Vogelstein conclude that these differences can be explained by the number of stem cell divisions. By plotting the lifetime incidence of various cancers against the estimated number of normal stem cell divisions in the corresponding tissues over a lifetime, they found a strong correlation extending over five orders of magnitude. This suggests that random errors occurring during DNA replication in normal stem cells are a major contributing factor in cancer development. Remarkably, this “bad luck” component explains a far greater number of cancers than do hereditary and environmental factors."

So in summary, the situation is very confused!

Summary of evidence reviewing Cancer and Alcoholic drinks

Food, nutrition, physical activity and the prevention of cancer WCRF/AICR

In 2007 the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published the results of an analysis of the effects of food, nutrition and physical activity based on a pooling of many hundreds of clinical trials.  The study was called "Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. This has been described as the most comprehensive report ever produced on the links between lifestyle and cancer risk and is the most notable source of information on the link between alcohol and cancer. The WCRF/AICR analysis is ongoing and the next report is due 2017.

In 2015 Klatsky AL et al published "Alcohol Intake, Beverage Choice, and Cancer: A Cohort Study in a Large Kaiser Permanente Population" and reported that "With lifelong abstainers as referent, heavy drinking (≥ 3 drinks per day) was associated with increased risk of 5 cancer types: upper airway/digestive tract, lung, female breast, colorectal, and melanoma, with light-to-moderate drinking related to all but lung cancer. No significantly increased risk was seen for 12 other cancer sites: stomach, pancreas, liver, brain, thyroid, kidney, bladder, prostate, ovary, uterine body, cervix, and hematologic system. For all cancers combined there was a progressive relationship with all levels of alcohol drinking. These associations were largely independent of smoking, but among light-to-moderate drinkers there was evidence of confounding by inferred underreporting. Beverage choice played no major independent role."

Klatsky concluded "Heavy alcohol drinking is related to increased risk of some cancer types but not others. Because of probable confounding, the role of light-to-moderate drinking remains unclear."

Bowel cancer - increased risk at greater than 30g of alcohol per day but a mixed picture

The WCRF report states that "The evidence that consumption of alcohol of more than 30g/day of ethanol from alcoholic drinks is a cause of colorectal cancer in men is convincing, and probably also in women."

Cho et al in 2004 in their paper "Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies" saw that "In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. "

In 2007, Ferrari et al reported on the link between rectal and colon cancers in Europe concluding that "In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day."

The 2009 Park JY et al with participants from Norfolk concluded that "Total alcohol consumption was not associated with CRC risk before or after adjustment for age, sex, weight, height, and smoking status . No significant associations were observed between consumption of specific alcoholic beverages (beer, sherry, or spirits) and CRC risk when compared with non-drinkers after adjustment for lifestyle and dietary factors. Daily consumption of > or =1 unit of wine appeared inversely related to CRC risk (HR: 0.61, 95% CI: 0.40-0.94). No evidence was found for sex-specific relationships, and further exclusion of cases incident within 3 years of baseline did not change the associations observed. In this population-based UK cohort, we did not find any significant adverse effect of alcohol over the moderate range of intake on colorectal cancer risk.". So a 40% lower risk with daily consumption of wine!

In the 2010 UK study by Park et al, which looked at alcohol intake and risk of colorectal cancer (CRC) concluded that "No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. " (up to 30g/day).

Hjartaker et al in 2013 looked at "subsite specific dietary risk factors for Colorectal cancer: A review of cohort studies" . The paper stated that "Ten articles were included in the review. Three analyses for both sexes combined consistently showed a higher risk of rectal cancer with increasing alcohol consumption and no significant associations for any of the colon subsites . In the EPIC studyan increased risk was reported both for rectal and distal colon cancer, whereas in the UK dietary cohort consortium (part of which is included in the EPIC study) a significantly increased risk was found for distal colon cancer only."

Breast cancer - contradictory in part but appears to be evidence that alcohol increases relative risk at levels over 30g of alcohol per day

The WCRF report confirms high heterogenicity (inconsistent findings) between studies, "Twelve cohort studies investigated ethanol intake and all-age breast cancer.Eight cohort studies showed increased risk for the highest intake group when compared to the lowest which was statistically significant in six.Four studies showed decreased risk which was statistically significant in one. Meta-analysis was possible on nine cohort studies, giving a summary effect estimate of 1.10 (95% CI 1.06–1.14) per 10 g/day, with high heterogeneity. Heterogeneity could be partly explained by differential adjustment for age and reproductive history."

Kuper et al in 2000 "Alcohol and breast cancer risk: the alcoholism paradox" reported that "A population-based cohort study of 36 856 women diagnosed with alcoholism in Sweden between 1965 and 1995 found that alcoholic women had only a small 15% increase in breast-cancer incidence compared to the general female population. It is therefore apparent, contrary to expectation, that alcoholism does not increase breast-cancer risk in proportion to presumed ethanol intake."

In 2006 Terry et al reported on lifetime alcohol intake and breast cancer risk, stating "Consumption of 15-30 grams/day (approximately one to two drinks) throughout life was associated with a modest 33% increase in risk (odds ratio [OR] = 1.33, 95% confidence interval (CI) = 1.01-1.74), but heavier consumption (> or = 30 grams per day) was not. Risk did not vary with alcohol type (beer, wine, or hard liquor) or by patterns of use, such as recent use, intake prior to age 20 years, or whether use began at an early age. The association with lifetime intake was limited to women with a BMI < 25 (OR = 2.13, 95% CI = 1.29-3.54).".

Mørch et al 2007 published "Alcoholic drinking, consumption patterns and breast cancer amongst Danish nurses:a cohort study" stated that "The relative risk of breast cancer was 2.30 [Confidence interval (CI): 1.56–3.39] for alcohol intake of 22–27 drinks per week, compared to 1–3 drinks per week. Among alcohol consumers, weekly alcohol intake increased the risk of breast cancer with 2% for each additional drink consumed. Weekend consumption increased the risk with 4% for each additional drink consumed friday through sunday. Binge drinking of 4–5 drinks the latest weekday increased risk with 55%, compared with consumption of one drink. A possible threshold in risk estimates was found for consumption above 27 drinks per week. Conclusions: For alcohol consumption above the intake most frequently reported, the risk of breast cancer is increased. The risk is minor for moderate levels but increases for each additional drink consumed during the week. Weekend consumption and binge drinking imply an additional increase in breast cancer risk." 

*However, nurses who drank small amounts of alcohol reduced breast cancer risk compared with abstainers, an effect which persisted to 24g per day. Between 24 and 36g per day, risk doubled and then fell back to +25% over 36g. 

In 2008 Barnett et al in the paper, "Risk factors for the incidence of breast cancer: do they affect survival from the disease?" said that "Improved prognosis was seen with increasing current alcohol consumption, with a 2% (95% CI, 1% to 3%) reduction in the risk of death per unit of alcohol consumed per week."

Bessaoud et al in 2008 published "Patterns of alcohol (especially wine) consumption and breast cancer risk: a case-control study among a population in Southern France" and reported that "Women who had an average consumption of less than 1.5 drinks per day had a lower risk (odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.34-0.97) when compared with nondrinkers. This protective effect was due substantially to wine consumption since the proportion of regular wine drinkers is predominant in our study population. Furthermore, women who consumed between 10 and 12 g/d of wine had a lower risk (OR = 0.51; 95% CI = 0.30-0.91) when compared with non-wine drinkers. Above 12 g per day of wine consumption, the risk of breast cancer increased, but the association was non-significant.

no association between the pattern of total alcohol consumption and breast cancer was found, the type of alcoholic beverage seemed to play an important role in this association. Our results support the hypothesis that there is a threshold effect that risk decreased or was not modified for consumption under a certain threshold. Above that threshold, risk increased, however. The drinking pattern of each type of specific beverage, especially wine, seems important in terms of alcohol-breast cancer association. Low and regular wine consumption does not increase breast cancer risk."

Chen et al in 2011 looked at moderate alcohol consumption and breast cancer risk reporting that " Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week (relative risk, 1.15; 95% CI, 1.06-1.24; 333 cases/100,000 person-years). Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk."

Chen also published in 2011, "Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk." and reported "During 2.4 million person-years of follow-up, 7690 cases of invasive breast cancer were diagnosed. Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week (relative risk, 1.15; 95% CI, 1.06-1.24; 333 cases/100,000 person-years). Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk." and "Low levels of alcohol consumption were associated with a small increase in breast cancer risk, with the most consistent measure being cumulative alcohol intake throughout adult life. Alcohol intake both earlier and later in adult life was independently associated with risk."

Schutze et al 2011 "Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study" reported that " If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women."

*Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Participants 109 118 men and 254 870 women, mainly aged 37-70.

In 2013 McDonald et al published "Alcohol Intake and Breast Cancer Risk: Weighing the Overall Evidence" and concluded that "Moderate alcohol consumption has been linked to an approximate 30-50% increased risk in breast cancer. Case-control and cohort studies have consistently observed this modest increase. We highlight recent evidence from molecular epidemiologic studies and studies of intermediate markers like mammographic density that provide additional evidence that this association is real and not solely explained by factors/correlates of the exposure and outcome present in non-randomized studies. "

Liver Cancer - unclear as to the risks due to variable data but wine would appear to have little or no effect

The WCRF report states that there is "high heterogenicity" with a "dose response relationship apparent in case control but not cohort data".

"Data are available from 15 cohort studies. Eleven cohort studies showed increased risk for the highest intake group when compared to the lowest,which was statistically significant in two.Two studies showed non-significant decreased risk. Two studies stated that there was no significant difference but did not provide further data.. Heterogeneity is partially explained by differences in whether and how studies have adjusted for hepatitis virus status. Data are available from 33 case-control studies. Twenty-eight case-control studies showed increased risk for the highest intake group when compared to the lowest,which was statistically significant in 12 (one of these studies reported a non-significant decreased risk in women, but a statistically significant increased risk in men).Two studies showed non-significant decreased risk. Three studies stated that there was no significant effect on risk. Metaanalysis was possible on five studies, giving a summary effect estimate of 1.18 (95% CI 1.11–1.26) per drink/week, with high heterogeneity. A dose-response relationship is apparent from case-control but not cohort data."

"Three cohort studies and one case-control study reported separately on wine drinking. One cohort study showed non-significant increased risk with increased intake. Two studies stated that there was no significant effect on risk.The single case-control study showed non-significant increased risk."

Kidney (Renal) Cancer - evidence that alcohol reduces risk

The WCRF state state that "It is unlikely that alcohol increases the risk of kidney cancer, though a protective effect cannot be excluded".

Lee et al in 2007 reported on "Alcohol intake and renal cancer in a pooled analysis of 12 prospective studies" that in "A total of 1430 (711 women and 719 men) cases of incident renal cell cancer were identified. The study-standardized incidence rates of renal cell cancer were 23 per 100,000 person-years among nondrinkers and 15 per 100,000 person-years among those who drank 15 g/day or more of alcohol. Compared with nondrinking, alcohol consumption (> or = 15 g/day, equivalent to slightly more than one alcoholic drink per day) was associated with a decreased risk of renal cell cancer (pooled multivariable RR = 0.72, 95% confidence interval = 0.60 to 0.86; P(trend)<.001); statistically significant inverse trends with increasing intake were seen in both women and men. No difference by sex was observed (P(heterogeneity) = .89). Associations between alcohol intake and renal cell cancer were not statistically different across alcoholic beverage type (beer versus wine versus liquor) (P = .40)." and concluding  that "Moderate alcohol consumption was associated with a lower risk of renal cell cancer among both women and men in this pooled analysis."

Pelucchi C et al in 2008 in "Alcohol consumption and renal cell cancer risk in two Italian case control studies" reported "Compared with non-drinkers, the multivariate odds ratios (ORs) of RCC were 0.87 [95% confidence interval (CI) 0.73–1.04] for ≤4 drinks per day, 0.76 (95% CI 0.59–0.99) for >4 to ≤8 drinks per day and 0.70 (95% CI 0.50–0.97) for >8 drinks per day of alcoholic beverages, with a significant inverse trend in risk (P value = 0.01). The ORs were 0.85 (95% CI 0.71–1.02) for wine, 0.84 (95% CI 0.68–1.03) for beer and 0.86 (95% CI 0.70–1.05) for spirits consumption, as compared with abstainers. No trend in risk of RCC emerged with duration (P value = 0.94) and age at starting alcohol consumption (P value = 0.81). Results were consistent in men and women, as well as in strata of age, smoking and body mass index.". Pelucchi concluded that "This pooled analysis found an inverse association between alcohol drinking and RCC. Risks continued to decrease even above eight drinks per day (i.e. >100 g/day) of alcohol intake, with no apparent levelling in risk."

Stomach (Gastric) Cancer - evidence that moderate alcohol drinkers have lower incidence and particularly wine drinkers

Barstad B et al 2005 in "Intake of wine, beer and spirits and risk of gastric cancer" reported "The objective was to study prospectively the relation between quantity and type of alcohol and risk of gastric cancer. In a pooled database from three population studies conducted in 1964-1992, a total of 15,236 men and 13,227 women were followed for a total of 389,051 person-years. During follow-up 122 incident cases of gastric cancer were identified. Total alcohol intake itself was not associated with gastric cancer, but type of alcohol seemed to influence risk. Compared with non-wine drinkers, participants who drank 1-6 glasses of wine had a relative risk ratio of 0.76 (95% confidence interval (CI) 0.50-1.16), whereas those who drank >13 glasses of wine per week had a relative risk ratio of 0.16 (95% CI 0.02-1.18). Linear trend test showed a significant association with a relative risk ratio of 0.60 (95% CI 0.39-0.93) per glass of wine drunk per day. These relations persisted after adjustment for age, gender, educational level, body mass index, smoking habits, inhalation and physical activity. There was no association between beer or spirits drinking and gastric cancer." and  "In conclusion, the present study suggests that a daily intake of wine may prevent development of gastric cancer. "

Duell EJ et al 2011 "Alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort" reported that "Heavy (compared with very light) alcohol consumption (≥60 compared with 0.1-4.9 g/d) at baseline was positively associated with GC risk (HR: 1.65; 95% CI: 1.06, 2.58), whereas lower consumption amounts (<60 g/d) were not. When we analyzed GC risk by type of alcoholic beverage, there was a positive association for beer (≥30 g/d; HR: 1.75; 95% CI: 1.13, 2.73) but not for wine or liquor. Associations were primarily observed at the highest amounts of drinking in men and limited to noncardia subsite and intestinal histology; no statistically significant linear dose-response trends with GC risk were observed.", and concluded that "Heavy (but not light or moderate) consumption of alcohol at baseline (mainly from beer) is associated with intestinal-type noncardia GC risk in men from the EPIC cohort."

Tramacere I et al published in 2012 "A meta analysis on alcohol drinking and gastric cancer risk" reported "Compared with nondrinkers, the pooled relative risk (RR) was 1.07 [95% confidence interval (CI) 1.01-1.13] for alcohol drinkers and 1.20 (95% CI 1.01-1.44) for heavy alcohol drinkers (≥4 drinks per day). The pooled estimates were apparently higher for gastric noncardia (RR for heavy drinkers=1.17, 95% CI 0.78-1.75) than for gastric cardia (RR=0.99, 95% CI 0.67-1.47) adenocarcinoma. The dose-risk model estimated a RR of 0.95 (95% CI 0.91-0.99) for 10 g/day and 1.14 (95% CI 1.08-1.21) for 50 g/day." and concluded that "This meta-analysis provides definite evidence of a lack of association between moderate alcohol drinking and gastric cancer risk. There was, however, a positive association with heavy alcohol drinking."

Gullet, throat, mouth (oesophageal, mouth, larynx, pharynx) Cancer - link with alcohol but small compared with smoking and evidence that wine has no effect

The WCRF state "There is ample and consistent evidence, both from case-control and cohort studies, with a dose-response relationship. There is robust evidence for mechanisms operating in humans. The evidence that alcoholic drinks are a cause of mouth, pharynx, and larynx cancers is convincing. Alcohol and tobacco together increase the risk of these cancers more than either acting independently. No threshold was identified."

On  mouth, pharynx, and larynx cancers "Twenty-six case-control studies and four ecological studies reported separately on wine drinking. Most of the case-control studies showed increased risk with increased intake which was statistically significant in less than half. Five studies showed decreased risk,which was statistically significant in one. Meta-analysis was possible on 11 case-control studies, giving a summary effect estimate of 1.02 (95% CI 1.01–1.03), with high heterogeneity.All studies adjusted for smoking. All four ecological studies showed statistically significant increased risk."

On Oesophagus and wine "Ten case-control studies,one crosssectional study and five ecological studies reported separately on wine drinking. All but one of the case-control studies showed increased risk with increased intake,which was statistically significant in seven.About half of the studies adjusted for smoking. The single cross-sectional study showed non-significant increased risk. Most ecological."

Prostate Cancer - evidence of reduced risk with wine

Schoonen WM 2005, "Alcohol consumption and risk of prostate cancer in middle-aged men." reported that "No clear association with prostate cancer risk was seen for overall alcohol consumption. Each additional glass of red wine consumed per week showed a statistically significant 6% decrease in relative risk (OR = 0.94; 95% CI = 0.90-0.98), and there was evidence for a decline in risk estimates across increasing categories of red wine intake (trend p = 0.02). No clear associations were seen for consumption of beer or liquor. Our present study suggests that consumption of beer or liquor is not associated with prostate cancer. There may be, however, a reduced relative risk associated with increasing level of red wine consumption. Further research is needed to evaluate the potential negative association between red wine intake and prostate cancer risk."