Genetic variation in the androgen estrogen conversion pathway in relation to breast cancer prognosticators.
Genetic variation in the androgen-to-estrogen conversion pathway has been shown to be associated with risk of breast cancer and, in particular, with estrogen receptor (ER) positive tumours. We aimed at studying how the genetic alterations, which have been identified for risk, are associated with breast cancer prognosticators, with a prior hypothesis that, in general, hormone-related breast cancers have a better prognosis than non-hormone-related breast cancers. Association between tagging SNPs in genes involved in estrogen metabolism and patient's lymph node status, tumour size and histological grade were estimated in a sample of 1569 Swedish breast cancer patients. Polymorphisms in CYP19A1, which have previously been linked to breast cancer risk, are shown to be associated with breast cancer prognosticators. The strongest association was observed for rs4646, with histological grade. The common allele of rs4646, which has been associated with increased breast cancer risk, was associated with low-histological grade and small tumour size (P = 0.001 and 0.015; 1-sided, respectively). We also found evidence that SNP rs7167936 is associated with histological grade and tumour size (P = 0.010 and 0.005; 1-sided, respectively). We show that rs4646 and rs7167936 are associated with histological grade even amongst only ER-positive tumours (P = 0.008 and 0.011; 1-sided, respectively). Our results provide new evidence that CYP19A1 is involved in both breast cancer risk and prognosis.
Darabi
Hatef
H
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. hatef.darabi@ki.se
Czene
Kamila
K
Wedrén
Sara
S
Li
Yuqing
Y
Liu
Jianjun
J
Hall
Per
P
Humphreys
Keith
K
D000368:Aged; D000728:Androgens / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D004967:Estrogens / Q000235:genetics / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis
D000728:Androgens; D014408:Biomarkers, Tumor; D004967:Estrogens