Alcohol-induced breast cancer: A proposed mechanism

Alcohol consumption increases the risk for breast cancer in women by still undefined means. Alcohol metabolism is known to produce reactive oxygen spe cies (ROS), and breast cancer is associated with high levels of hydroxyl ra dical ((OH)-O-.) modified DNA, point mutations, single strand nicks, and ch romosome rearrangement. Furthermore, ROS modification of DNA can produce th e mutations and DNA damage found in breast cancer. Alcohol dehydrogenase (A DH) and xanthine oxidoreductase (XOR) are expressed and regulated in breast tissues and aldehyde oxidase (AOX) may be present as well. Mammary gland X OR is an efficient source of ROS. Recently, hepatic XOR and AOX were found to generate ROS in two ways from alcohol metabolism: by acetaldehyde consum ption and by the intrinsic NADH oxidase activity of both XOR and AOX. The d ata obtained suggests that: (1) expression of ADH and XOR or AOX in breast tissue provides the enzymes that generate ROS; (2) metabolism of alcohol pr oduces acetaldehyde and NADH that can both be substrates for XOR or AOX and thereby result in ROS formation; and (3) ROS generated by XOR or AOX can i nduce the carcinogenic mutations and DNA damage found in breast cancer. Acc umulation of iron coupled with diminished antioxidant defenses in breast ti ssue with advancing age provide additional support for this hypothesis beca use both result in elevated ROS damage that may exacerbate the risk for ROS -induced breast cancer. (C) 1998 Elsevier Science Inc.