Study of the Relationship between ERCC1 Polymorphisms and Response to Platinum-based Chemotherapy in Iranian Patients with Colorectal and Gastric Cancers

Document Type: Research article

Authors

1 Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medial Sciences, Tehran, Iran.

2 Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Ayatollah Taleghani Hospital, Shahid Beheshti University of Medial Sciences, Tehran, Iran.

4 Department of Radiation Oncology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Food Safety Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

This study was designed to evaluate the effect of excision repair cross
complementing group 1 (ERCC1) rs11615 codon 118C/T gene polymorphisms on
treatment outcomes in Iranian patients receiving oxaliplatin-based regimens for
colorectal (CRC) and gastric cancers (GC). Patients, who were candidates to receive
oxaliplatin-based chemotherapy, entered into the study. In 2-week intervals, the
patients received combination regimen of oxaliplatin, fluorouracil, and leucovorin
(FOLFOX) for 3 months. ERCC1 rs11615 codon 118C/T polymorphism was tested
by restriction fragment length polymorphism polymerase chain reaction (RFLPPCR)
method using patients’ peripheral blood lymphocytes. The tumor response to
chemotherapy was evaluated by examining the size of the tumor using CT scan.
Association between response rates, according to the RECIST criteria, and patients’
genotypes was evaluated. Any relationship between response rate and possible
explanatory factors was also determined. Overall, 40 patients (13 females (32.5%),
and 27 males (67.5%)) enrolled in the study. Four patients (10.0%) carried the homozygous
mutation (T/T genotype), ten patients (25.0%) were heterozygous (C/T
genotype), and twenty-six patients (65%) were homozygous (C/C genotype).
Response rate were 30.77%, 20.00%, and 0.00% for the genotypes C/C, C/T, and
T/T, respectively. No significant association between response rate and genotypes
was observed (p = 0.64). Patients with well- and moderately-differentiated
histological grade of the tumor showed a better response rate (100.00% of 2 patients
and 66.66% of 12 patients, respectively) compared to those with poorly
differentiated (0.00% of 26 patients) histological grade (p < 0.001). Further
multicenter studies are recommended to confirm conclusively our findings.

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