title: Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness.
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. Genotyping 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. For one 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. Analysis 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.
authors: Molecular Cancer Epidemiology group, Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors: Felicity
authors: F
authors: Lose
authors: Jyotsna
authors: J
authors: Batra
authors: Tracy
authors: T
authors: O'Mara
authors: Paul
authors: P
authors: Fahey
authors: Louise
authors: L
authors: Marquart
authors: Ros A
authors: RA
authors: Eeles
authors: Douglas F
authors: DF
authors: Easton
authors: Ali Amin
authors: AA
authors: Al Olama
authors: Zsofia
authors: Z
authors: Kote-Jarai
authors: Michelle
authors: M
authors: Guy
authors: Kenneth
authors: K
authors: Muir
authors: Artitaya
authors: A
authors: Lophatananon
authors: Aneela A
authors: AA
authors: Rahman
authors: David E
authors: DE
authors: Neal
authors: Freddie C
authors: FC
authors: Hamdy
authors: Jenny L
authors: JL
authors: Donovan
authors: Suzanne
authors: S
authors: Chambers
authors: Robert A
authors: RA
authors: Gardiner
authors: Joanne F
authors: JF
authors: Aitken
authors: John
authors: J
authors: Yaxley
authors: Kimberly
authors: K
authors: Alexander
authors: Judith A
authors: JA
authors: Clements
authors: Amanda B
authors: AB
authors: Spurdle
authors: Mary-Anne
authors: MA
authors: Kedda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007610:Kallikreins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
chemical_list: C497170:KLK12 protein, human; C470778:KLK13 protein, human; C400147:KLK5 protein, human; C103551:KLK6 protein, human; D007610:Kallikreins