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ABSTRACT: GSTM1 and GSTT1 polymorphisms and postmenopausal breast
cancer risk
Glutathione S-transferases (GSTs) are a family of important
enzymes involved in the detoxification of a wide variety of known
and suspected carcinogens, including potential mammary carcinogens
identified in charred meats and tobacco smoke.
A substantial
proportion of the Caucasian population has a homozygous deletion
(null) of the GSTM1 or GSTT1 gene, which results in lack of
production of these isoenzymes.
We conducted a case-control study
in a cohort of postmenopausal Iowa women who in 1986 completed a
mailed questionnaire on lifestyle factors including information on
cigarette smoking and breast cancer risk factors. DNA samples and
information related to charred meat intake were obtained, in the
case-control study, from breast cancer cases diagnosed during
1992-1994, and a random sample of cancer-free cohort members.
Included in this study were 202 cases and 481 controls who were
genotyped for GSTM1 or GSTT1 gene polymorphisms. Compared to
women who had both GSTM1 and GSTT1 genes, a 60% elevated risk
(95% CI = 1.0-2.5) was observed among those whose GSTM1 or GSTT1
gene was deleted.
When stratified by meat eating habits, the risk
of breast cancer associated with null GSTM1 or GSTT1 genotype
was observed primarily among women who ate meats consistently
well- or very well-done. Women who carried either one of the
null genotypes and consumed meat consistently well- or very
well-done had a 3.4-fold elevated risk of developing breast
cancer (95% CI = 1.6-7.1).
Cigarette smoking was not a risk
factor for breast cancer among women who had either the GSTM1
or GSTT1 genes. Among those with the null GSTT1 genotype, however,
a significantly elevated risk of breast cancer was associated
with cigarette smoking (OR = 2.5, 95% CI = 1.1-5.4) and the
association was stronger among former (OR = 4.4, 95% CI = 1.5-12.8)
than current smokers (OR = 1.3, 95% CI = 0.4-4.1).
This study
suggests that certain null GST genotypes may be associated with
an elevated risk of breast cancer and the association may be
modified by charred meat intake and cigarette smoking.
[07/16/2002; Breast Cancer Research and Treatment]
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