SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness

Abstract

BACKGROUND-Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk.

Estrogen receptor β and the progression of prostate cancer: role of 5α-androstane-3β,17β-diol

“…Therefore, at least in the early stages of PC, 3b-Adiol formation may shift the equilibrium versus a slowing down of progression and invasiveness of the tumor cells. This exciting hypothesis has strong support in clinical observations, demonstrating that genetic alteration of several enzymes involved in androgenic steroid metabolism is linked to hereditary and sporadic PC susceptibility (Chang et al 2002, Steckelbroeck et al 2004, Bauman et al 2006, Cunningham et al 2007, Neslund-Dudas et al 2007, Park et al 2007, Ross et al 2008, Beuten et al 2009, Mindnich & Penning 2009). It has been established that enzyme responsible for 3b-Adiol formation from the DHT in prostate is AKR1C1; in fact, AKR1C1:AKR1C2 (responsible for 3a-diol formation from the DHT) transcript ratio fells in PC; thus, the data here presented provide clear explanations of these observations, since the reduction of 3b-Adiol levels in favor of 3a-Adiol may be a risk factor for PC in these patients, because the 3b-Adiol 'protective' effect will obviously disappear.…”

Intraethnic variation in steroid-5-alpha-reductase polymorphisms in prostate cancer patients: a potential factor implicated in 5-alpha-reductase inhibitor treatment

“…Second, the study was focussed on SRD5A1 and SRD5A2, ignoring possible associations with other genes and polymorphisms. Thus, the prostate cancer risk and aggressiveness conferred by certain SNPs located in 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) seem to be modified by SNPs located in SRD5A2 (Neslund-Dudas et al 2007). In the same way, an association between SNPs in CYP17A1 (a gene encoding a key enzyme in the synthesis of androgens) and SRD5A2 has been suggested (Onen et al 2007).…”

Validation of a sequential extraction and liquid chromatography–tandem mass spectrometric method for determination of dihydrotestosterone, androstanediol and androstanediol–glucuronide in prostate tissues

“…Some groups have looked at the association of PCa and polymorphisms in UGT enzymes, namely UGT2B15 and UGT2B17 [30][31][32][47][48][49]. Besides the UGTs, polymorphisms in the HSD3B2 gene along with the SRD5A2 and SRD5A1 have also been associated with PCa risk and aggressiveness [50,51]. Little is known about the impact of allelic variants on PCa development and progression for the remaining metabolic enzymes (Fig.…”