Alcohol drinking and mammary cancer: Pathogenesis and potential dietary preventive alternatives

Abstract

Alcohol consumption is associated with an increased risk of breast cancer, increasing linearly even with a moderate consumption and irrespectively of the type of alcoholic beverage. It shows no dependency from other risk factors like menopausal status, oral contraceptives, hormone replacement therapy, or genetic history of breast cancer. The precise mechanism for the effect of drinking alcohol in mammary cancer promotion is still far from being established. Studies by our laboratory suggest that acetaldehyde produced in situ and accumulated in mammary tissue because of poor detoxicating mechanisms might play a role in mutational and promotional events. Additional studies indicated the production of reactive oxygen species accompanied of decreases in vitamin E and GSH contents and of glutathione transferase activity. The resulting oxidative stress might also play a relevant role in several stages of the carcinogenic process. There are reported in literature studies showing that plasmatic levels of estrogens significantly increased after alcohol drinking and that the breast cancer risk is higher in receptor ER-positive individuals. Estrogens are known that they may produce breast cancer by actions on ER and also as chemical carcinogens, as a consequence of their oxidation leading to reactive metabolites. In this review we introduce our working hypothesis integrating the acetaldehyde and the oxidative stress effects with those involving increased estrogen levels. We also analyze potential preventive actions that might be accessible. There remains the fact that alcohol drinking is just one of the avoidable causes of breast cancer and that, at present, the suggested acceptable dose for prevention of this risk is of one drink per day.

Keywords: Acetaldehyde; Alcohol; Estrogens; Ethanol; Free radicals; Mammary cancer; Oxidative stress; Polyphenols.

Figure 1

Cooperative mechanism between NADPH oxidase and lipoxygenase in the oxidation of ethanol to acetaldehyde in microsomes.

Figure 2

Structures of some of acetaldehyde-guanine adducts.

Figure 3

Structures of adducts formed between DNA bases and (A) malondialdehyde or (B) 4-hydroxy-2-nonenal.

Figure 4

Estrogen oxidation to reactive metabolites that bind to DNA to generate depurinating adducts.

Figure 5

Pathways for catechol-estrogen methylation by carboxymethyl transferase.

Figure 6

Working hypothesis about the mechanism of the promotion of mammary cancer by alcohol drinking.

Figure 7

Structures of some of the compounds with the most powerful ability to inhibit the oxidation of ethanol to acetaldehyde in rat mammary tissue microsomal and cytosolic fractions.

Figure 8

Reaction between acetaldehyde and cysteine to form the adduct 2-methylthiazolidine-4-carboxylic acid.