Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study.
BACKGROUND
Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk.


METHODS
We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data.


RESULTS
There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant.


CONCLUSIONS
We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.
Wedrén
Sara
S
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. sara.wedren@meb.ki.se
Lovmar
Lovisa
L
Humphreys
Keith
K
Magnusson
Cecilia
C
Melhus
Håkan
H
Syvänen
Ann-Christine
AC
Kindmark
Andreas
A
Landegren
Ulf
U
Fermér
Maria Lagerström
ML
Stiger
Fredrik
F
Persson
Ingemar
I
Baron
John
J
Weiderpass
Elisabete
E
D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics*
D047628:Estrogen Receptor alpha; D005819:Genetic Markers; D011960:Receptors, Estrogen