An intronic variant in PTEN is not associated with prostate cancer risk.

Introduction Loss of heterozygosity at chromosome 10q23–25 and allelic loss of the PTEN gene is frequently observed in prostate tumors, which suggests that this locus is a target of inactivation. PTEN, a tumor suppressor gene, encodes a dual-specificity phosphatase whose primary function appears to be the dephosphorylation of the second messenger PIP3 (1). The absence of PTEN expression in prostate tumors is highly correlated with Gleason score and advanced stage and appears to play a role in prostate cancer progression (2). Germ-line mutations in PTEN cause the autosomal dominant Cowden and Bannayan-RileyRuvalcaba syndromes (3). Cancer predisposition in Cowden syndrome is limited primarily to breast and thyroid cancers. However, mice deficient in PTEN develop prostate cancer (4). Therefore, germ-line mutations in PTEN primarily predispose to breast cancer, but somatic mutations in PTEN are more commonly observed in prostate cancer (3). No common polymorphisms in the coding region of PTEN have been reported. However, several intronic variants have been identified, including a 5-bp insertion (TCTTA) at IVS41109. IVS4 immediately precedes exon 5, which contains the phosphatase core domain, and is a “hot spot” for germ-line mutations. This-5 bp insertion has been associated with earlier age of breast cancer onset in variant homozygotes compared with wild-type heterozygotes or homozygotes (5). This variant has been found at higher frequencies in tumors of various organs than in germ-line samples (5, 6). Because PTEN is somatically mutated in prostate tumors and the 5-bp intronic insertion polymorphism is more commonly found in tumor than in germ-line specimens, we hypothesized that it could be involved in the etiology of prostate cancer.