
Validation of micro RNA pathway polymorphisms in esophageal adenocarcinoma survival
Author(s) -
Faluyi Olusola O.,
Eng Lawson,
Qiu Xin,
Che Jiahua,
Zhang Qihuang,
Cheng Dangxiao,
Ying Nanjiao,
Tse Alvina,
Kuang Qin,
Dodbiba Lorin,
Renouf Daniel J.,
Marsh Sharon,
Savas Sevtap,
Mackay Helen J.,
Knox Jennifer J.,
Darling Gail E.,
Wong Rebecca K. S.,
Xu Wei,
Azad Abul Kalam,
Liu Geoffrey
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.989
Subject(s) - medicine , hazard ratio , adenocarcinoma , esophageal adenocarcinoma , cohort , proportional hazards model , oncology , esophageal cancer , gastroenterology , cancer , confidence interval
Polymorphisms in mi RNA and mi RNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate mi RNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 mi RNA targets, 5 pri‐mi RNA , 7 pre‐mi RNA ) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival ( OS ) and progression‐free survival ( PFS ). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN 3 rs197412 ( aHR = 1.37, 95% CI : [1.04–1.80]; P = 0.02), hsa‐mir‐124‐1 rs531564 ( aHR = 0.60, 95% CI : [0.53–0.90]; P = 0.05), and KIAA 0423 rs1053667 ( aHR = 0.51, 95% CI : [0.28–0.96]; P = 0.04) were found associated with OS . Furthermore, GEMIN 3 rs197412 ( aHR = 1.33, 95% CI : [1.03–1.74]; P = 0.03) and KRT 81 rs3660 ( aHR = 1.29, 95% CI : [1.01–1.64]; P = 0.04) were found associated with PFS . Although none of these polymorphisms were significant in the second cohort, hsa‐mir‐124‐1 rs531564 and KIAA 0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN 3 rs197412 , hsa‐mir‐124‐1 rs531564 , and KIAA 0423 rs1053667 remained significantly associated with OS . We demonstrate the association of multiple mi RNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort but had consistent associations in the pooled cohort. Larger studies are required to confirm/validate the prognostic value of these polymorphisms in esophageal adenocarcinoma.