Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer

Abstract

MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol dehydrogenase II was assessed in serum from 467 randomly selected German women and 278 women with invasive breast cancer to evaluate the interaction between a polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk for breast cancer. In both groups, usual consumption of different alcoholic beverages was asked for using semiquantitative food frequency questionnaires. We used multivariable logistic regression to separately estimate the association between alcohol consumption and alcohol dehydrogenase II polymorphism in the population sample and women with breast cancer. The alcohol dehydrogenase II polymorphism was detected in 14 women from the population sample (3.0%) and in 27 women with invasive breast cancer (9.7%). Frequency of alcohol consumption was independent of the genotype in the population sample. In women with breast cancer, there was a significant inverse association between the alcohol dehydrogenase II polymorphism and frequency of alcohol consumption (adjusted case-only odds ratio over increasing frequency of alcohol consumption=0.5; P for interaction=0.02). We observed a gene-environment interaction between the alcohol dehydrogenase II polymorphism, alcohol consumption, and risk for breast cancer. Breast cancer risk associated with alcohol consumption may vary according to the alcohol dehydrogenase II polymorphism, probably due to differences in alcohol metabolism. British Journal of Cancer (2002) (Longnecker, 1994;Smith-Warner et al, 1998;Singletary and Gapstur, 2001;Willett, 2001). Despite growing interest in genetic polymorphisms of the enzymes involved in alcohol metabolism for several diseases associated with alcohol comsumption (Hines et al, 2001;McCarver, 2001; Yamauchi et al, 2001a,b), data regarding the role of these polymorphisms as to the risk for breast cancer are sparse (Freudenheim et al, 1999;Hines et al, 2000). These polymorphisms are good candidates for gene-environment interactions (Millikan et al, 1995), however, because they are likely to influence the most plausible biologic mechanism linking alcohol consumption to risk for breast cancer, i.e. endogenous oestrogens.In humans, alcohol is almost entirely metabolised by oxidative detoxification, mainly dependent on two enzymes, class I alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). Both enzymes exhibit genetic polymorphisms influencing the rate of conversion from alcohol to acetaldehyde and to acetate (Smith, 1986). The class I ADH isoenzymes are formed by dimeric associations of a, b, and g subunits controlled by three separate gene loci ADH1, ADH2, and ADH3, respectively (Agarwal and Goedde, 1990). Despite recent reports regarding the ADH3 polymorphism and risk for breast cancer (Freudenheim et al, 1999;Hines et al, 2000), nothing is known about the role of the less frequent but metabolically more relevant ADH2 polymorphism and its interaction with alcohol consumption for the risk of breast cancer.The aim of the ...

Alcohol dehydrogenase 1B (ADH1B) genotype, alcohol consumption and breast cancer risk by age 50 years in a German case–control study

“…Owing to the small number of ADH1B*2 carriers, we were not able to further subdivide the highest alcohol intake category of X12 g day À1 . Corresponding to a previous case-only study (Sturmer et al, 2002), a case-only analysis of our data would yield a statistically significant interaction OR (OR 0.2, 95% CI 0.1 -0.6 for X12 g alcohol day À1 ). However, since ADH1B genotype and alcohol intake are not independent in our study population, the modifying effect of the ADH1B genotype on breast cancer risk associated with alcohol consumption is overestimated in the case-only analysis, partly due to residual confounding by differences in alcohol consumption caused by the genotype (Albert et al, 2001).…”

“…Previously, a significant inverse association between the ADH1B*2 allele and frequency of alcohol consumption was observed in a case-only study (Sturmer et al, 2002). We employed a population-based case -control study of women up to age 50 years to examine the potential effect of ADH1B genotype on the association between alcohol consumption and breast cancer risk.…”

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

“…One study reported an increased risk of breast cancer among premenopausal, but not postmenopausal, women who were ADH3*1 homozygotes (Freudenheim et al 1999), while another study found no such association (Hines et al 2000). The most recent study found an interaction between the ADH2*2 allele in Caucasian women and alcohol consumption among patients with breast cancer (Sturmer et al 2002). The ADH2*2 allele was more common in the women with breast cancer.…”

Alcohol dehydrogenase 1B genotype and fetal alcohol syndrome: a HuGE minireview

“…88,[92][93][94][95][96][97] However, other studies identified ADH1B*2 as a risk factor. Sturmer et al 98 found that ADH1B*2 was more common in women with breast cancer, despite the fact that those with ADH1B*2 drank less. However, in Lilla et al, 99 ADH1B*2 was associated with decreased risk of breast cancer as alcohol consumption increased, while ADH1B*1 was associated with increased risk with higher alcohol consumption.…”