Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.

H19 is an imprinted gene coding for an oncofetal RNA that is down-regulated postnatally. Reactivation of the H19 gene has been observed in bladder tumors, and H19 expression has been associated with early recurrence of disease. In this study we examined whether sequence variants within the H19 gene are associated with the risk of developing bladder cancer.

Five tagging single nucleotide polymorphisms (tagSNPs) covering the H19 gene and its promoter region were selected with the use of Haploview software. One hundred and seventy-seven bladder cancer patients who were referred to our university hospital were genotyped for these tagSNPs. The genotypes were compared with those of a random sample of 204 controls of the general population.

A significantly decreased risk of bladder cancer was found for the rs2839698 TC genotype (odds ratio [OR], 0.60; 95% confidence interval (95%CI), 0.36-0.99), but not for CC homozygotes. The rs2839698 TC genotype was especially associated with a reduced risk of developing non-muscle-invasive disease (OR, 0.52; 95%CI, 0.28-0.94). Borderline significantly decreased risks of bladder cancer were found for the rs2107425 CT genotype (OR, 0.66; 95%CI, 0.43-1.00), but not for TT homozygotes or for T allele carriers of rs217727 (OR, 0.74; 95%CI, 0.51-1.06). Haplotype analysis did not result in stronger associations with bladder cancer compared with the single-locus analyses.

An SNP polymorphism in the non-protein-encoding H19 gene is associated with a decreased risk of developing non-muscle-invasive bladder cancer. This association was found for only heterozygotes, not for homozygotes.

Written by
Verhaegh GW, Verkleij L, Vermeulen SH, den Heijer M, Witjes JA, Kiemeney LA.

Reference
Eur Urol. 2008 Feb 4. Epub ahead of print.
doi:10.1016/j.eururo.2008.01.060

PubMed Abstract
PMID:18262338

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