title: A polymorphism of the POLG2 gene is genetically associated with the invasiveness of urinary bladder cancer in Japanese males.
abstract: Urinary bladder cancer (UBC) is a common cancer with male predominance. Pathologically it is classified into two distinct tumor entities related to the risk of patients. The low-grade tumors with relatively well-differentiated tumor histology (G1 and G2) at stage Ta are non-invasive and pose a minimal risk, whereas high-grade tumors (G2 and G3) with stages T1 to T4 are aggressive with invasion, and therefore, pose a serious risk for the patients. DNA repair and metabolic process genes may have major roles in cancer progression and development. To identify genes associated with invasiveness of UBC, we have extensively genotyped 802 single nucleotide polymorphisms in 114 genes related to DNA repair mechanisms and metabolic processes. A genetic association study was performed between non-invasive (G1 and G2 with Ta) and invasive (G2 and G3 with T1 to T4) groups of Japanese UBC patients. We found that rs17650301 in POLG2 showed marked difference in genotype distribution between the two groups in males (P=6.93 × 10(-4)), which was further confirmed in an independent sample set (overall P=1.67 × 10(-4)). We also found by an in silico analysis that the risk allele of rs17650301 increased the transcription of POLG2. In conclusion, rs17650301 is a good candidate marker for UBC invasiveness in Japanese males.
authors: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Yoshida, Kyoto, Japan.
authors: Chanavee
authors: C
authors: Ratanajaraya
authors: Hiroyuki
authors: H
authors: Nishiyama
authors: Meiko
authors: M
authors: Takahashi
authors: Takahisa
authors: T
authors: Kawaguchi
authors: Ryoichi
authors: R
authors: Saito
authors: Yoshiki
authors: Y
authors: Mikami
authors: Mikita
authors: M
authors: Suyama
authors: Mark
authors: M
authors: Lathrop
authors: Ryo
authors: R
authors: Yamada
authors: Osamu
authors: O
authors: Ogawa
authors: Fumihiko
authors: F
authors: Matsuda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
chemical_list: D004259:DNA-Directed DNA Polymerase; C544932:POLG2 protein, human