Evaluation of miR-27a, miR-181a, and miR-570 genetic variants with gallbladder cancer susceptibility and treatment outcome in a North Indian population.
BACKGROUND
miR-27a, miR-181a, and miR-570 genetic variants have been found to play an important role in many cancers, but their contribution in gallbladder carcinoma (GBC) has not been explored. Therefore, we investigated the role of these micro RNA (miRNA) genetic variants in terms of GBC susceptibility, therapeutic response, toxicities associated with chemo-radiotherapy and survival outcome.


METHODS
This study included 606 GBC patients and 200 healthy controls. From among the larger study cohort, 219 patients receiving adjuvant or palliative chemo-radiotherapy as per disease status were followed up for toxicity profile. Treatment response was recorded in 159 patients who received palliative chemo-radiotherapy. Genotypes were determined using allelic discrimination assay. Statistical analysis was carried out with SPSS version 16. Generalized multifactor dimensionality reduction (GMDR) analysis was performed for gene-gene interactions. Survival analysis was performed using Kaplan-Meier and Cox regression tests.


RESULTS
In univariate logistic regression analysis, no association with any of the studied polymorphisms was found in overall GBC susceptibility. Furthermore, univariate and multivariate analyses revealed no significant association with response to chemo-radiotherapy. In GMDR analysis, miR-27ars895819, miR-570rs4143815, and miR-181ars12537 combination was found as the best gene-gene interaction model for susceptibility and treatment response. Furthermore, miR-27ars895819miR-181ars12537 was associated with neutropenia toxicity in patients undergoing chemo-radiotherapy. However, miRNA variants had no influence over the survival outcomes of GBC patients (locally advanced, metastatic).


CONCLUSIONS
In conclusion, the miRNA variants cumulatively influence GBC susceptibility and treatment outcomes.
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India.
Annapurna
A
Gupta
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India.
Aarti
A
Sharma
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India.
Anu
A
Yadav
Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Neeraj
N
Rastogi
Department of Radiotherapy, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Sushma
S
Agrawal
Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Ashok
A
Kumar
Department of Surgical Oncology, King George's Medical University, Lucknow, India.
Vijay
V
Kumar
Department of Surgical Oncology, King George's Medical University, Lucknow, India.
Sanjeev
S
Misra
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India. bml_pgi@yahoo.com.
Balraj
B
Mittal
D000328:Adult; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
C531388:MIRN27 microRNA, human; C582115:MIRN570 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs