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Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women
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Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women
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Journal Article
Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women
2010
Overview
Recent findings indicate a greater risk of postmenopausal breast cancer with estrogen–progestagen therapy than estrogen monotherapy, and more so for current than past use. Few studies have examined individual genetic susceptibility to the effects of menopausal hormone therapy. We used two population-based case-control studies with 3,155 postmenopausal breast cancer patients and 5,496 controls to evaluate modification of breast cancer risk associated with duration of hormone use by genes involved in hormone metabolism and detoxification. Twenty-eight polymorphisms in eight genes of phase I (
CYP1A1
,
CYP1A2
,
CYP1B1
,
CYP2C9
,
CYP2C19
,
CYP3A4
,
CYP3A5
,
CYP3A7
) and nine genes of phase II enzymes (
COMT
,
GSTM1
,
GSTM3
,
GSTP1
,
GSTT1
,
SULT1A1
,
UGT1A1
,
UGT1A6
,
UGT2B7
) were genotyped. The risk associated with duration of use of combined estrogen–progestagen therapy was significantly modified by genetic polymorphisms located in
CYP1B1, GSTP1
, and
GSTT1
. In homozygote carriers of the
CYP1B1
_142_G and the
CYP1B1
_355 _T variant alleles, adjusted odds ratios (OR) per year of use were 1.06 (95% confidence interval (CI) = 1.02–1.09) and 1.06 (95% CI = 1.03–1.09), respectively, compared with 1.02 (95% CI = 1.01–1.03) in non-carriers of either polymorphism (
p
interaction
= 0.01). Carriers of the functional
GSTT1
allele and the
GSTP1
_341_T allele were at significantly higher risks associated with hormone use compared with non-carriers (
p
interaction
= 0.0001 and 0.02).
CYP1A1
_2452_C>A significantly reduced the risk associated with duration of use of estrogen monotherapy (
p
interaction
= 0.01). The finding regarding GSTT1 was still statistically significant after corrections for multiple comparisons. Postmenopausal breast cancer risk associated with hormone therapy may be modified by genetically determined variations in phase I and II enzymes involved in steroid hormone metabolism.
Publisher
Springer US,Springer,Springer Nature B.V
Subject
/ Biological and medical sciences
/ Breast Neoplasms - chemically induced
/ Breast Neoplasms - enzymology
/ Breast Neoplasms - epidemiology
/ Enzymes
/ Estrogen
/ Estrogen Replacement Therapy - adverse effects
/ Female
/ Gene Expression Regulation, Enzymologic
/ Genes
/ Genetic Predisposition to Disease
/ Gynecology. Andrology. Obstetrics
/ Humans
/ Medicine
/ Metabolic Detoxication, Phase I - genetics
/ Metabolic Detoxication, Phase II - genetics
/ Oncology
/ Progestins - adverse effects
/ Tumors
