DNA repair gene polymorphisms may be associated with prognosis of upper urinary tract transitional cell carcinoma

Abstract

Upper urinary tract transitional cell carcinoma (UUT-TCC) is quite an uncommon disease, and its prognosis differs among individuals irrespective of tumor stage. DNA repair gene polymorphisms are reported to result in the modulation of the repair capacity and might influence the prognosis of UUT-TCC. We examined the associations between functional polymorphisms in five DNA repair genes, and the prognosis of UUT-TCC in 103 UUT-TCC patients. Variant alleles in xeroderma pigmentosum complementation group C, more than three total variant alleles in all DNA repair genes studied and more than two total variant alleles in three nucleotide excision repair genes were independently associated with improved overall and disease-specific survival of UUT-TCC patients in multivariate analysis (P = .0063 and P = .0005 for xeroderma pigmentosum complementation group C, P = .016 and P = .0016 for all genes, and P = .0053 and P = .018 for nucleotide excision repair genes, respectively). These results suggest that some DNA repair gene polymorphisms may preoperatively be valuable as prognostic factors for UUT-TCC beyond tumor stage and grade, helping to provide optimal treatment strategies for individual patients.

Figure 1

Kaplan-Meier overall survival curves for patients with UUT-TCC by DNA repair genotypes (log-rank tests). (A) Lys/Gln + Gln/Gln versus Lys/Lys of XPC; P = .0016. (B) His/His versus Asp/Asp + Asp/His of XPG; P = .016. (C) Total variant alleles in all DNA repair genes studied: > 3 versus ≤ 3; P = .019. (D) Total variant alleles in NER genes (XPC, XPD, and XPG): > 2 versus ≤ 2; P = .0035.

Figure 2

Kaplan-Meier disease-specific survival curves for patients with UUT-TCC by DNA repair genotypes (log-rank tests). (A) Lys/Gln + Gln/Gln versus Lys/Lys of XPC; P = .0032. (B) His/His versus Asp/Asp + Asp/His of XPG; P = .069. (C) Total variant alleles in all DNA repair genes studied: > 3 versus ≤ 3; P = .012. (D) Total variant alleles in NER genes (XPC, XPD, and XPG): > 2 versus ≤ 2; P = .0066.