RGD Reference Report - Androgen metabolism and JAK/STAT pathway genes and prostate cancer risk. - Rat Genome Database

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Androgen metabolism and JAK/STAT pathway genes and prostate cancer risk.

Authors: Kwon, EM  Holt, SK  Fu, R  Kolb, S  Williams, G  Stanford, JL  Ostrander, EA 
Citation: Kwon EM, etal., Cancer Epidemiol. 2012 Aug;36(4):347-53. Epub 2012 Apr 26.
RGD ID: 6893648
Pubmed: PMID:22542949   (View Abstract at PubMed)
PMCID: PMC3392409   (View Article at PubMed Central)
DOI: DOI:10.1016/j.canep.2012.04.002   (Journal Full-text)

BACKGROUND: Prostate cancer (PC) is the most frequently diagnosed solid tumor in U.S. men. Genome-wide association studies (GWAS) have identified over 40 risk-associated single nucleotide polymorphisms (SNPs), including variants in androgen pathway genes (e.g., KLK3 and AR). Androgens are important in PC and genes involved in this pathway are therefore candidates for conferring susceptibility to PC. METHODS: In this hypothesis-testing study, we evaluated PC risk in association with SNPs in 22 candidate genes involved in androgen metabolism or interactions with the androgen receptor (AR). A total of 187 SNPs were genotyped in 1458 cases and 1351 age-matched controls from a population-based study. PC risk was estimated using adjusted unconditional logistic regression and multinomial regression models. RESULTS: Single SNP analyses showed evidence (p < 0.05) for associations with 14 SNPs in 9 genes: NKX3.1, HSD17B3, AKR1C3, SULT2A1, CYP17A1, KLK3, JAK2, NCOA4 and STAT3. The most significant result was observed for rs2253502 in HSD17B3 (odds ratio, OR = 0.57, 95% CI: 0.39-0.84). In addition, five SNPs in four genes (CYP17A1, HSD17B4, NCOA4, and SULT2A1) were associated with more aggressive disease (p < 0.01). CONCLUSIONS: Our results replicate previously reported associations for SNPs in CYP17A1, HSD17B3, ARK1C3, NKX3.1, NCOA4 and KLK3. In addition, novel associations were observed for SNPs in JAK2, HSD17B4, and SULT2A1. These results will require replication in larger studies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer severityIAGP 6893648DNA:SNP:intron: (rs2547238) (human)RGD 
prostate cancer severityISOSULT2A1 (Homo sapiens)6893648; 6893648DNA:SNP:intron: (rs2547238) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Prostate cancer severityIAGP 6893648DNA:SNP:intron: (rs2547238)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Sult2a1  (sulfotransferase family 2A member 1)

Genes (Mus musculus)
Sult2a1  (sulfotransferase family 2A, dehydroepiandrosterone (DHEA)-preferring, member 1)

Genes (Homo sapiens)
SULT2A1  (sulfotransferase family 2A member 1)


Additional Information