Sk. Park et al., Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk, PHARMACOGEN, 10(4), 2000, pp. 301-309
To evaluate the potential association between GSTM1 and GSTT1 genotypes and
development of breast cancer, a hospital based case-control study was cond
ucted in a South Korean study population consisting of 189 histologically c
onfirmed incident breast cancer cases and their 189 age-matched control sub
jects with no present or previous history of cancer. A multiplex polymerase
chain reaction method was used for the genotyping analyses and statistical
evaluations were performed by unconditional logistic regression model. The
GSTM1 null genotype was significantly associated with breast cancer risk i
n premenopausal women [odds ratio (OR) = 2.0, 95% confidence interval (CI)
= 1-3.7], but not in the postmenopausal women (OR = 0.9, 95% CI = 0.5-1.9),
nor in all women grouped together (OR = 1.3, 95% CI = 0.8-1.1). The GSTT1
null genotype posed a similar risk of breast cancer with an OR of 1.6 (95%
CI = 1.0-2.5) for the total breast cancer group, OR of 1.7 (95% CI = 0.9-3.
2) for pre-menopausal women, and OR of 1.3 (95% CI = 0.6-2.8) for post-meno
pausal women. The breast cancer risk associated with concurrent lack of bot
h GSTM1 and GSTT1 genes was 2.2 (95% CI = 1.1-4.5), and the risk increased
as the number of null genotype increased (P for trend = 0.03). When the dat
a were stratified by the known risk factors of breast cancer, a significant
interaction was observed between the GSTM1 genotypes and alcohol consumpti
on (P for interaction = 0.03). An especially remarkable risk of breast canc
er was observed for alcohol-consuming premenopausal women lacking both the
GSTM1 and GSTT1 genes (OR = 5.3, 95% CI = 1.0-27.8) compared to those with
both of the genes. Our findings thus suggest a novel gene-environment inter
action which plays an important role in the individual susceptibility to br
east cancer. Pharmacogenetics 10:301-309 (C) 2000 Lippincott Williams & Wil
kins.