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Polymorphisms in the BRCA1 and ABCB1 genes modulate menopausal hormone therapy associated breast cancer risk in postmenopausal women
Ist Teil von
Breast cancer research and treatment, 2010-04, Vol.120 (3), p.727-736
Ort / Verlag
Boston: Springer US
Erscheinungsjahr
2010
Quelle
MEDLINE
Beschreibungen/Notizen
Menopausal hormone therapy (HT) is associated with an increased breast cancer risk among postmenopausal women. In this study, we investigated genetic effect modification of HT associated breast cancer risk in 3,149 postmenopausal breast cancer patients and 5,489 controls from the two German population-based case–control studies MARIE and GENICA. Twenty-eight polymorphisms of 14 candidate genes including two drug and hormone transporter genes (
ABCB1/MDR1
and
SHBG
), four genes involved in cell cycle regulation (
BRCA1
,
P21/CDKN1A
,
STK15/AURKA
and
TP53
), six cytokine genes (
IGFBP3
,
IL6,
TGFB1
,
TNF
,
LTA
and
IGF1
), and two cytokine receptor genes (
EGFR
and
ERBB2
) were genotyped using validated methods. Conditional logistic regression was used to assess multiplicative statistical interaction between polymorphisms and duration of estrogen–progestagen therapy and estrogen monotherapy use with regard to breast cancer risk assuming log-additive and co-dominant modes of inheritance. Women homozygous for the major
ABCB1
_rs2214102_G allele were found to be at a significantly increased breast cancer risk associated with combined estrogen–progestagen therapy [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.12–1.23,
P
interaction
= 0.022]. Additionally, risk associated with estrogen monotherapy was modified by
BRCA1
_rs799917. We observed a trend with increasing minor T alleles leading to the highest risk in homozygous carriers of the minor allele [OR (95% CI) = 1.17 (0.98–1.39), 1.06 (0.98–1.14), and 1.02 (0.94–1.11) for homozygous minor, heterozygous, and homozygous major allele carriers, respectively;
P
interaction
= 0.032]. Our results suggest that genetic variants in
ABCB1
and
BRCA1
may modify the effect of HT on postmenopausal breast cancer risk.