Genetic variation in the HSD17B1 gene and risk of prostate cancer

Abstract

Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17b-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor D5-androsterone-3b,17b-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p , 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites.Citation: Kraft P, Pharoah P, Chanock SJ, Albanes D, Kolonel LN, et al. (2005) Genetic variation in the HSD17B1 gene and risk of prostate cancer. PLoS Genet 1(5): e68.

Role of Hormonal and Other Factors in Human Prostate Cancer

“…concentrations (Chen et al, 2003) but an Australian cohort study showed no association with baseline plasma E2 levels (Severi et al, 2006). A large international pooled analysis yielded no evidence for an association with polymorphisms of the HSD17B1 gene, which encodes the 17HSD type 1 enzyme that converts estrone to the more active E2 (Kraft et al, 2005).…”

Integrated mRNA and miRNA expression profile analyses reveal the potential roles of sex‐biased miRNA–mRNA pairs in gonad tissues of the Chinese concave‐eared torrent frog (Odorrana tormota)

“…P 450 aromatase (CYP17A1), which is expressed in granulosa cells, converts androstenedione (A) and testosterone (T) to estrone (E1) and 17β‐estrone (E2), respectively. Meanwhile, HSD17B1 encodes a member of the 17β‐HSD family that converts estrone into estradiol in ovarian tissue (Kraft et al, ). Granulosa cells respond to FSH signaling by increasing the expression of CYP17A1 and 17β‐HSD.…”

HSD17B1 Genetic Variants and Hormone Receptor–Defined Breast Cancer

“…htSNPs were selected based on the efforts of the Breast and Prostate Cohort Consortium (BPC3) (15), as previously described (12, 16). Given the close proximity of the adjacent genes, including N-acetylglucosaminidase-α ( NAGLU ) gene and a pseudogene for HSD17B1 ( HSD17BP1 ) in the 5′ direction and CoA synthase ( COASY ) and transcription factor-like 4 ( TCFL4 ) in the 3′ direction, the location of htSNPs for HSD17B1 extended into these neighboring genes.…”