Author/Authors :
Lose، نويسنده , , Felicity and Batra، نويسنده , , Jyotsna and OʹMara، نويسنده , , Tracy and Fahey، نويسنده , , Paul and Marquart، نويسنده , , Louise and Eeles، نويسنده , , Ros A. and Easton، نويسنده , , Douglas F. and Al Olama، نويسنده , , Ali Amin and Kote-Jarai، نويسنده , , Zsofia and Guy، نويسنده , , Michelle and Muir، نويسنده , , Kenneth and Lophatananon، نويسنده , , Artitaya and Rahman، نويسنده , , Aneela A. and Neal، نويسنده , , David E. and Hamdy، نويسنده , , Freddie C. and Donovan، نويسنده , , Jenny L. and Chambers، نويسنده , , Suzanne and Gardiner، نويسنده , , Robert A. and Aitken، نويسنده , , Joanne F. and Yaxley، نويسنده , , John and Alexander، نويسنده , , Kimberly and Clements، نويسنده , , Judith A. and Spurdle، نويسنده , , Amanda B. and Kedda، نويسنده , , Mary-Anne، نويسنده ,
Abstract :
The human tissue Kallikrein family consists of 15 genes with the majority shown to be differentially expressed in cancers and/or indicators of cancer prognosis. We sought to elucidate the role of common genetic variation in four of the Kallikrein genes, KLK5, KLK6, KLK12, and KLK13, in prostate cancer risk and tumor aggressiveness.
ping of all 22 tagging single nucleotide polymorphisms (tagSNPs) in the KLK5, KLK6, KLK12, and KLK13 genes was performed in approximately 1,000 prostate cancer cases and 1,300 male controls from Australia. Data from any positive results were also accessed for 1,844 cases and 1,886 controls from a previously published prostate cancer genome-wide association study set from the United Kingdom.
e SNP in KLK12, rs3865443, there was evidence for association with prostate cancer risk of similar direction and magnitude in the replication set to that seen in the Australian cohort. We conducted genotyping of a further 309 prostate cancer cases, and combined analyses revealed an increased risk of prostate cancer for carriers of the rare homozygous genotype for rs3865443 (OR 1.28, 95% CI 1.04–1.57; P = 0.018). No other tagSNPs in the KLK5, KLK6, and KLK13 genes were consistently associated with prostate cancer risk or tumor aggressiveness.
is of a combined sample of 3,153 cases and 3,199 controls revealed the KLK12 tagSNP rs3865443 to be marginally statistically significantly associated with risk of prostate cancer. Considering the total number of SNPs investigated in this study, this finding should be interpreted cautiously and requires additional validation from very large datasets such as those of the Prostate Cancer Association group to investigate cancer associated alterations (PRACTICAL) Consortium.
