Variation in CYP Gene Links Estrogen Level, Breast Cancer Risk

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(ChemotherapyAdvisor) – Variation in a metabolism gene is associated with risk of breast cancer development in premenopausal women, according to researchers of the Institute of Cancer Research, London, UK. The study, entitled “CYP3A Variation, Premenopausal Estrone Levels, and Breast Cancer Risk,” was published online on April 3 in the Journal of the National Cancer Institute.

The researchers aimed to identify common variants in genes involved in sex steroid synthesis or metabolism that are associated with hormone levels and the risk of breast cancer in premenopausal women. In 729 premenopausal women, urinary levels of estrone glucuronide (E1G), a metabolite of estrogen, were measured using a protocol that accounted menstrual cycle related variation in estrogen levels. Six hundred forty-two (642) women were genotyped for several single-nucleotide polymorphisms (SNPs). A single SNP, rs10273424, was further tested for association with the risk of breast cancer using data from 10,551 breast cancer case patients and 17,535 control subjects. Data were analyzed using two-sided statistical tests.

Study researchers reported that rs10273424, which maps close to the cytochrome P450 3A (CYP3A) gene, “was associated with a 21.8% reduction in E1G levels (95% confidence interval [CI]=27.8% to 15.3% reduction; P=2.7×10−9) and a modest reduction in the risk of breast cancer in case patients who were diagnosed at or before age 50 years (odds ratio [OR]=0.91, 95% CI=0.83 to 0.99; P=.03) but not in those diagnosed after age 50 years (OR=1.01, 95% CI=0.93 to 1.10; P=.82).”

The researchers concluded: “Genetic variation in noncoding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and is associated with the risk of breast cancer in younger patients. This association may have wider implications given that the most predominantly expressed CYP3A gene, CYP3A4, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents used in the treatment of breast cancer.”


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