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From SNPedia
Geno Mag Summary
(A;A) 0 common in clinvar
(C;C) 0 common/normal
Make rs4646(A;C)
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (old)rs4646
1000 genomesrs4646
23andMe allrs4646
GWAS Ctlgrs4646
Max Magnitude0

rs4646 is a SNP in the CYP19A1 gene on chromosome 15.

The CYP19A1 gene is probably the primary one studied to date as possibly associated with the efficacy or toxicity of aromatase inhibitors such as letrozole, anastrozole and exemestane. The effect of CYP19A1 variant in response to such inhibitors has produced conflicting results in studies (see citations below), and although rs4646 may be perhaps the best studied CYP19A1 variant, there is to date no robust or replicated conclusion about it with respect to aromatase inhibitor response.[PMID 26203310OA-icon.png]

? (A;A) (A;C) (C;C) 28
[PMID 19366906] BRCA1 Breast Cancer Risk Is Modified by CYP19 Polymorphisms in Ashkenazi Jews

[PMID 19438456] Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss

[PMID 19478482] Genetic variation of CYP19 (aromatase) gene influences age at onset of Alzheimer's disease in women

[PMID 20144226OA-icon.png] rs4646(A) allele carriers with breast cancer being treated with letrozole are reported to do worse than rs4646(C;C) patients, based on a study of (only) 95 women.

[PMID 26067721OA-icon.png] Based on a meta-analysis of (only) two studies, one involving treatement with letrozole and the other anastrozole, rs4646(A) allele carriers with metastatic breast cancer showed a greater time to progression (TTP) compared to rs4646(C;C) patients, indicating overall a possible benefit to being an (A) allele carrier.

[PMID 20960227] Genetic variation in the androgen estrogen conversion pathway in relation to breast cancer prognosticators

[PMID 22511967OA-icon.png] Potential Role of Aromatase over Estrogen Receptor Gene Polymorphisms in Migraine Susceptibility: A Case Control Study from North India

[PMID 16412218OA-icon.png] Multilocus analysis of SNP and metabolic data within a given pathway.

[PMID 18049890] Single nucleotide polymorphisms of the aromatase gene (CYP19A1), HER2/neu status, and prognosis in breast cancer patients.

[PMID 18199708OA-icon.png] Haplotype analyses of CYP19A1 gene variants and breast cancer risk: results from the Shanghai Breast Cancer Study.

[PMID 18274619OA-icon.png] Association study of aromatase gene (CYP19A1) in essential hypertension.

[PMID 18603647OA-icon.png] Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.

[PMID 18622258OA-icon.png] Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones among postmenopausal Chinese women.

[PMID 18654799OA-icon.png] Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease.

[PMID 18941913OA-icon.png] Coffee intake, variants in genes involved in caffeine metabolism, and the risk of epithelial ovarian cancer.

[PMID 19015200OA-icon.png] Polymorphisms in estrogen- and androgen-metabolizing genes and the risk of gastric cancer.

[PMID 19064562OA-icon.png] Genetic variation in CYP19A1 and risk of breast cancer and fibrocystic breast conditions among women in Shanghai, China.

[PMID 19152063] Polymorphisms in estrogen metabolism and estrogen pathway genes and the risk of miscarriage.

[PMID 19168589OA-icon.png] Variants in hormone-related genes and the risk of biliary tract cancers and stones: a population-based study in China.

[PMID 19194457OA-icon.png] Association between arterial stiffness and variations in oestrogen-related genes.

[PMID 19794821OA-icon.png] Anastrozole Use in Early Stage Breast Cancer of Post-Menopausal Women.

[PMID 20819792] Association of CYP19 and ESR1 pleiotropic genes with human longevity.

[PMID 21269619] Epistasis between FSHR and CYP19A1 polymorphisms is associated with premature ovarian failure.

[PMID 22638611] Estrogen synthesis genes CYP19A1, HSD3B1, and HSD3B2 in hypertensive disorders of pregnancy.

[PMID 23129173OA-icon.png] Plasma estrone sulfate concentrations and genetic variation at the CYP19A1 locus in postmenopausal women with early breast cancer treated with letrozole

[PMID 23700878] Research on aromatase gene (CYP19A1) polymorphisms as a predictor of endocrine therapy effectiveness in breast cancer

[PMID 24324964OA-icon.png] CYP19 Genetic Polymorphism Haplotype AASA Is Associated with a Poor Prognosis in Premenopausal Women with Lymph Node-Negative, Hormone Receptor-Positive Breast Cancer

[PMID 23408108OA-icon.png] Regulation of aromatase expression in breast cancer treated with anastrozole neoadjuvant therapy.

[PMID 23540392OA-icon.png] Impact of aromatase genetic variation on hormone levels and global outcome after severe TBI.

[PMID 25793413OA-icon.png] The CYP19 RS4646 Polymorphism IS Related to the Prognosis of Stage I-II and Operable Stage III Breast Cancer

[PMID 26379441OA-icon.png] No associations between aromatase gene polymorphisms and breast cancer risk in Saudi patients

[PMID 26463708OA-icon.png] Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy

[PMID 27825388OA-icon.png] Impact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial.

Risk Rs4646(C;C)
Alt Rs4646(C;C)
Reference Rs4646(A;A)
Significance Non-pathogenic
Disease Aromatase deficiency
Variation info
Gene CYP19A1
CLNDBN Aromatase deficiency
Reversed 0
HGVS NC_000015.9:g.51502844A>C
CLNACC RCV000363053.1,