TRPV6 alleles do not influence prostate cancer progression.
BACKGROUND
The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca(2+) selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage.


METHODS
Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test.


RESULTS
We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage.


CONCLUSIONS
Our results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients are not significantly different. Although expression of trpv6 transcripts correlates with aggressive potential of prostate cancer, the TRPV6 genotype does not correlate with the onset of prostate cancer, with the Gleason score and the tumour stage.
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany. kesslerthorsten@googlemail.com
Thorsten
T
Kessler
Ulrich
U
Wissenbach
Rainer
R
Grobholz
Veit
V
Flockerzi
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D000483:Alleles; D015220:Calcium Channels / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D044469:Racial Groups / Q000235:genetics; D050916:TRPV Cation Channels / Q000235:genetics*
D015220:Calcium Channels; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human