The consumption of alcohol has been identified as one of the top-10 risks contributing to the worldwide burden of disease. The International Agency for Research on Cancer (IARC) has classified ethanol as carcinogenic to humans [91
]. Thus, the carcinogenic effects of alcoholic beverages are essentially due to their ethanol content and increase with the amount of alcohol drunk. Although the interpretation of data obtained in epidemiological studies is difficult due to confounding factors such as smoking, diet, hormone-replacement therapy and family history, the risks are essentially due to the ethanol content of alcoholic beverages. However, there is evidence that moderate wine consumption may decrease the risk of several cancers, including colon, basal cell carcinoma, ovarian and prostate cancer [92
Consumption of approximately 1 glass of wine daily was associated with a decreased risk of developing Barrett’s esophagus, a precursor to esophageal adenocarcinoma, when compared to heavy drinkers or non-drinkers [94
]. A meta-analysis found that modest wine consumption had an inverse association for developing lung cancer, for both average wine consumption of less than one drink per day (RR, 0.77; 95% CI, 0.59–1.00) and one drink or greater per day (RR, 0.78; 95% CI, 0.60–1.02) [95
]. A study of female non-Hodgkin’s lymphoma patients found a significantly better five-year overall survival (75% vs
. 69%) and five-year disease free survival (70% vs
. 67%) in occasional wine drinkers vs
. abstainers [96
]. Compared to non-drinkers, women who drank wine for at least 25 years previously were 33% less likely to die and 26% less likely to experience a relapse or develop a secondary cancer over the five-year period following diagnosis.
A large percentage of the literature on the cancer-preventing effects of wine are focused on one compound in particular: resveratrol. Many comprehensive reviews have been written on this subject [31
]. Wine may inhibit carcinogenesis by acting as an antioxidant, anti-inflammatory agent, antimutagen, antimetastatic, anti-angiogenic, antidifferentiation, antiproliferative, and proapoptotic agent. It modulates signal transduction, immune response, transcription factors, growth factors, cytokines, caspases, interleukins, prostaglandin synthesis and cell cycle-regulating proteins.
However, although there are few doubts as to the beneficial effects of moderate drinking on the cardiovascular system, only a limited number of reports concerning alcohol and cancer have provided results in favor of a reduced risk of death by cancer. According to the data of the Million Women study [87
] even light to moderate levels of alcohol consumption were predictive of an increased risk of several common cancers, mainly those of the breast. It has been suggested that alcohol intake increases circulating levels of estrogen and the production of reactive oxygen species during alcohol metabolism, inducing DNA damage that results in breast cancer [99
]. A recent study has reported that alcohol intake, the genes involved in alcohol metabolism and their interaction, increase the risk of breast cancer in post-menopausal women [101
]. In relation to the type of beverage (beer, wine or spirits), a prospective cohort study has reported that total alcohol intake of more than 27 drinks per week increases breast cancer risk in premenopausal women independently of the type of alcoholic beverage consumed [102
]. However, a low to moderate alcohol intake was not associated with increased mortality after breast cancer in a cohort of middle-aged women previously diagnosed with breast cancer [103
]. Additionally, the drinking pattern seems important in terms of alcohol-breast cancer association as some authors have suggested that low and regular wine consumption does not increase breast cancer risk [104
Several components of wine (mainly resveratrol) have shown anticarcinogenic properties in experimental studies [105
]. Those have been supported by its ability to inhibit proliferation of a wide variety of human tumor cells in vitro
as well as implanted tumors, usually in mice [97
]. However, it should be emphasized that these results are measurements of resveratrol responses on human cancer cells in culture, or taken as conclusions from epidemiological studies, rather than the results of clinical trials with cancer patients.
In the case of beer, xanthohumol is the best studied anticarcinogenic. It acts by inhibiting the metabolic activation of procarcinogenics, detoxifying enzyme inducers of carcinogens [25
] and inhibiting tumor growth in early stages through inhibition of angiogenesis and inflammatory signals. Other compounds in beer with anticarcinogenic capacity are 8-prenilnaringenin, isoxanthohumol (having 10–20-fold lower concentrations than the effective doses in humans in beer) and other prenilflavonoids, as well as the flavanones, humulones and proantocianidins [24
]. Considering that the bioavailability of the phenolic compounds of beer is very low, their anticarcinogenic effects are somewhat controversial as many epidemiological studies have shown [107
]. However, polyphenols from beer can reach low but effective concentrations in the colon, acting as local anti-carcinogenic agents. The iso-α-acids (humulones) represent one of the most abundant groups of polyphenols in beer and also possess antitumor activity. It has also been described that cohumola, n
-humulone and adhumulona activate receptors of α peroxisome proliferation (PPAR α), having potential activity in preventing cancer [23
Several epidemiological studies have investigated the potential role of beer as a cause of cancer due to the detection of volatile nitrosamines in beer, although amounts have been reported to be lower in more recent decades because of changes in the beer-making process [109
]. Since most epidemiological studies refer to long-term alcohol consumption, these studies cover, in part, periods of time before changes were made in the malting process. On the other hand, beer consumption (10 g alcohol/day) was reported to significantly decrease the risk of prostate cancer in comparison with non-drinking of beer in a Canadian study including 1253 subjects [112
Malt-derived beer components require further investigation. Studies with melanoidins, i.e.
, polymeric and colored final products of the Maillard reaction which are formed non-enzymatically during the roasting of malt, indicate peroxyl radical scavenging potential [114
]. Melanoidin fractions with a relatively high molecular weight (10→200 kDa) also weakly induced NADPHcytochrome C reductase and size-dependently modulated GST activities in the Caco-2 colon cancer cell line [116
]. The information available illustrates that beer is an extremely complex mixture of bioactive substances. Therefore, a thorough exploration of the chemopreventive activities of isolated prominent beer components seems to make eminent sense. Nevertheless, future studies should also focus on defined combinations to explore whether the mixture can be more efficacious than the single components.
Thus, the issue of alcohol and cancer is wide open and new studies are needed. Since self-reported data on alcohol consumption in epidemiological studies may not be reliable, especially in women, clinical studies on the effects of alcohol on health should be based on specific and accurate biomarkers of alcohol or wine/beer consumption such as ethanol (ethylglucoronide or ethylene glycol) or polyphenolic metabolites, respectively, in urine.