Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA

A missense substitution A49T in the steroid 5-alpha-reductase gene (SRD5A2) is not associated with prostate cancer in Finland

“…However, Makridakis et al (1999) recently documented in a casecontrol association study that the A49T mutation in the SRD5A2 gene may increase the risk of prostate cancer by a factor of 2.5 to 3.28, in Hispanic and in the African-American populations. The risk for clinically advanced disease were shown to be 3.6-fold and 7.2-fold, respectively (Makridakis et al, 1999). The authors estimated that A49T could account for as much as 8% of clinically significant prostate cancers.…”

“…Makridakis et al (1999) recently reported that the A49T variant was more common among 216 African-American and 172 Hispanic prostate cancer patients than in the corresponding ethically matched controls. The authors suggested that up to 8% of the clinically advanced prostate cancers in these populations could be attributable to this genetic variant (Makridakis et al, 1999). This finding is supported by the findings of Jaffe et al (2000), who reported that men who carry the A49T variant have prostate tumours that are more likely to exhibit extracapsular extension and higher pTNM stage than men who do not carry this variant.…”

“…A germline mis-sense substitution (A49T) leads to a variant SRD5A2 protein, which has a 5-fold higher in vitro V max than the wild-type protein (Ross et al, 1998;Makridakis et al, 1999). The A49T variant was recently associated with 2.5 to 3.28-fold increased risk of prostate cancer (PC) in African-American and Hispanic men (Makridakis et al, 1999).…”

“…A TA-dinucleotide repeat polymorphism at the 3′ UTR of SRD5A2 (Davis and Russell, 1993;Reichardt et al, 1995;Kantoff et al, 1997) and a valine to leucine substitution at codon 89 (Makridakis et al, 1997;Febbo et al, 1999;Lunn et al, 1999) have not been found to be associated with prostate cancer. A third polymorphism, alanine to threonine substitution at codon 49 (A49T) results in a variant 5-α-reductase enzyme with a V max of about 5 times that of the wild enzyme (Ross et al, 1998;Makridakis et al, 1999). Makridakis et al (1999) recently reported that the A49T variant was more common among 216 African-American and 172 Hispanic prostate cancer patients than in the corresponding ethically matched controls.…”

“…A third polymorphism, alanine to threonine substitution at codon 49 (A49T) results in a variant 5-α-reductase enzyme with a V max of about 5 times that of the wild enzyme (Ross et al, 1998;Makridakis et al, 1999). Makridakis et al (1999) recently reported that the A49T variant was more common among 216 African-American and 172 Hispanic prostate cancer patients than in the corresponding ethically matched controls. The authors suggested that up to 8% of the clinically advanced prostate cancers in these populations could be attributable to this genetic variant (Makridakis et al, 1999).…”