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 (P¼6.93Â10 À4 ), which was further confirmed in an independent sample set (overall P¼1.67Â10 À4 ). 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.

Systematic Review: Genetic Associations for Prognostic Factors of Urinary Bladder Cancer

“…For low-risk tumors, researchers used the following definitions: TaG2, 33,34 TaG1, 33 and TaG1-2. 12,14,17 In contrast, high-risk tumors were defined as TaG2-3 + T1G1-3, 25,30,31,40,76 TaG3 + T1G2-3, 24 G2-3 with T1-4, 77 and TaG3 + T1 33 (Supplementary Table 6).…”

Association studies getting broader: A commentary on A polymorphism of the POLG2 gene is genetically associated with the invasiveness of urinary bladder cancer in Japanese males

“…Genetics, Ratanajaraya et al 1 present a case-control association study to identify genes associated with the 'invasiveness' of urinary bladder cancer (UBC). The authors focused on assessing the genes related to DNA repair and metabolic pathways, and have successfully discovered a variant on the POLG2 gene associated with Japanese male UBC patients.…”