title: Genetic variants of the autophagy pathway as prognostic indicators for prostate cancer.
abstract: Autophagy is a complex process of autodigestion in conditions of cellular stress, and it might play an important role in the pathophysiology during carcinogenesis. We hypothesize that genetic variants of the autophagy pathway may influence clinical outcomes in prostate cancer patients. We genotyped 40 tagging single-nucleotide polymorphisms (SNPs) from 7 core autophagy pathway genes in 458 localized prostate cancer patients. Multivariate Cox regression was performed to evaluate the independent association of each SNP with disease progression. Positive findings were then replicated in an independent cohort of 504 advanced prostate cancer patients. After adjusting for known clinicopathologic factors, the association between ATG16L1 rs78835907 and recurrence in localized disease [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.54-0.90, P = 0.006] was replicated in more advanced disease (HR 0.78, 95% CI 0.64-0.95, P = 0.014). Additional integrated in silico analysis suggests that rs78835907 tends to affect ATG16L1 expression, which in turn is correlated with tumor aggressiveness and patient prognosis. In conclusion, genetic variants of the autophagy pathway contribute to the variable outcomes in prostate cancer, and discovery of these novel biomarkers might help stratify patients according to their risk of disease progression.
authors.affiliation: Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Huang
authors.affiliation: Department of Urology, E-Da Hospital, Kaohsiung, Taiwan.|School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Lin
authors.affiliation: Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Pharmacy, Tajen University, Pingtung, Taiwan.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Yu
authors.affiliation: Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan.
authors.forename: Ta-Yuan
authors.initials: TY
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Te-Ling
authors.initials: TL
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Chiang
authors.affiliation: Department of Pharmacy, China Medical University, Taichung, Taiwan.|Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.|Department of Nursing, Asia University, Taichung, Taiwan.
authors.forename: Bo-Ying
authors.initials: BY
authors.lastname: Bao
mesh_terms: D000368:Aged; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics; D015331:Cohort Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins