Polymorphisms in the H19 gene and the risk of bladder cancer.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Verhaegh
Gerald W
GW
Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Verkleij
Linda
L
Vermeulen
Sita H H M
SH
den Heijer
Martin
M
Witjes
J Alfred
JA
Kiemeney
Lambertus A
LA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D011379:Prognosis; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*
D004273:DNA, Neoplasm; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated