Bladder cancer SNP panel predicts susceptibility and survival

Abstract

Bladder cancer is the fourth most common malignancy in men and the eighth most common in women in western countries. Single nucleotide polymorphisms (SNPs) in genes that regulate telomere maintenance, mitosis, inflammation, and apoptosis have not been assessed extensively for this disease. Using a population-based study with 832 bladder cancer cases and 1,191 controls, we assessed genetic variation in relation to cancer susceptibility or survival. Findings included an increased risk associated with variants in the methyl-metabolism gene, MTHFD2 (OR 1.7 95% CI 1.3-2.3), the telomerase TEP1 (OR 1.8 95% CI 1.2-2.6) and decreased risk associated with the inflammatory response gene variant IL8RB (OR 0.6 95% CI 0.5-0.9) compared to wild-type. Shorter survival was associated with apoptotic gene variants, including CASP9 (HR 1.8 95% CI 1.1-3.0). Variants in the detoxification gene EPHX1 experienced longer survival (HR 0.4 (95% CI 0.2-0.8). These genes can now be assessed in multiple study populations to identify and validate SNPs appropriate for clinical use.

Fig. 1

Bladder cancer survival in relation to SNPs. Kaplan–Meier plots show survival (y-axis) versus years from diagnosis (x-axis) by a EPHX1_15 genotype, b IL8RB_01 genotype, c PGR_05 genotype, and d CASP9_01 genotype. Black lines are homozygous wildtype, red are homozygous variant, green are heterozygous