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.

Keywords

Main Subjects


Bradbury PA, Kulke MH, Heist RS, Zhou W, Ma
C, Xu W, Marshall AL, Zhai R, Hooshmand SM
and Asomaning K. Cisplatin pharmacogenetics,
DNA repair polymorphisms, and esophageal cancer
outcomes. Pharmacogenet. Genomics (2009) 19: 613-
25.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐Tieulent
J and Jemal A. Global cancer statistics, 2012. CA
Cancer J. Clin. (2015) 65: 87-108.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C and
Parkin DM. Estimates of worldwide burden of cancer
in 2008: GLOBOCAN 2008. Int. J. Cancer. (2010)
127: 2893-917.
Organization WH. World report on ageing and health.
World Health Organization (2015).
Hongo M, Nagasaki Y and Shoji T. Epidemiology
of esophageal cancer: Orient to Occident. Effects of
chronology, geography and ethnicity. J. Gastroenterol.
Hepatol. (2009) 24: 729-35.
Institute for Health Metrics and Evaluation. What
causes the most deaths? (2018) Available from: URL:
http://www.healthdata.org/iran.
Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar
M, Mulrow C, Woolf S, Glick S, Ganiats T and Bond
J. Colorectal cancer screening: clinical guidelines and
rationale. Gastroenterology (1997) 112: 594-642.
Grimes N, Devlin J, Dunne DF, Poston G, Fenwick
S and Malik H. The role of hepatectomy in the
management of metastatic gastric adenocarcinoma: a
systematic review. Surg. Oncol. (2014) 23: 177-85.
Zhao J, Nie Y, Wang H and Lin Y. miR-181a
suppresses autophagy and sensitizes gastric cancer
cells to cisplatin. Gene (2016) 576: 828-33.
André T, Boni C, Mounedji-Boudiaf L, Navarro M,
Tabernero J, Hickish T, Topham C, Zaninelli M,
Clingan P and Bridgewater J. Oxaliplatin, fluorouracil,
and leucovorin as adjuvant treatment for colon cancer.
N. Engl. J. Med. (2004) 350: 2343-51.
Sinicrope FA, Mahoney MR, Smyrk TC, Thibodeau
SN, Warren RS, Bertagnolli MM, Nelson GD,
Goldberg RM, Sargent DJ and Alberts SR. Prognostic
impact of deficient DNA mismatch repair in patients
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
 Abyarghamsari M et al. / IJPR (2019), 18 (4): 2163-2171
2170
with stage III colon cancer from a randomized trial
of FOLFOX-based adjuvant chemotherapy. J. Clin.
Oncol. (2013) 31: 3664-72.
Kuebler JP, Wieand HS, O′Connell MJ, Smith RE,
Colangelo LH, Yothers G, Petrelli NJ, Findlay MP,
Seay TE and Atkins JN. Oxaliplatin combined with
weekly bolus fluorouracil and leucovorin as surgical
adjuvant chemotherapy for stage II and III colon
cancer: results from NSABP C-07. J. Clin. Oncol.
(2007) 25: 2198-204.
Yu Y, Kanwar SS, Patel BB, Nautiyal J, Sarkar FH and
Majumdar AP. Elimination of colon cancer stem-like
cells by the combination of curcumin and FOLFOX.
Transl. Oncol. (2000) 2: 321-8.
Viguier J, Boige V, Miquel C, Pocard M, Giraudeau
B, Sabourin JC, Ducreux M, Sarasin A and Praz F.
ERCC1 codon 118 polymorphism is a predictive factor
for the tumor response to oxaliplatin/5-fluorouracil
combination chemotherapy in patients with advanced
colorectal cancer. Clin. Cancer Res. (2005) 11: 6212-7.
Raymond E, Faivre S, Woynarowski JM and
Chaney SG. Oxaliplatin: mechanism of action and
antineoplastic activity. Semin. Oncol. (1998) 25
(Suppl 5): 4-12.
Raymond E, Chaney S, Taamma A and Cvitkovic
E. Oxaliplatin: a review of preclinical and clinical
studies. Ann. Oncol. (1998) 9: 1053-71.
Liang J, Jiang T, Yao RY, Liu ZM, Lv HY and
Qi WW. The combination of ERCC1 and XRCC1
gene polymorphisms better predicts clinical outcome
to oxaliplatin-based chemotherapy in metastatic
colorectal cancer. Cancer Chemother. Pharmacol.
(2010) 66: 493-500.
Liu L, Li C, Jin T and Xu D. Study on the ERCC1
gene polymorphism response to chemotherapy and
prognosis of gastric cancer. Genet. Mol. Res. (2014)
13: 8722-8.
Filiptsova O, Kobets M and Kobets YN. Some aspects
of genetics and pharmacogenetics understanding by
pharmacy students in Ukraine. Egypt. J. Med. Hum.
Genet. (2015) 16: 61-6.
Davoodi H, Hashemi SR and Seow HF. 5-Fluorouracil
induce the expression of TLR4 on HCT116 colorectal
cancer cell line expressing different variants of TLR4.
Iran. J. Pharm. Res. (2013) 12: 453-60.
Kooshyar MM, Elyasi S, Marouzi A, Fani Pakdel A,
Taghizadeh-Kermani A, Akbarzadeh M and Aledavood
SA. Adherence to a standardized chemotherapy order
form for colorectal cancer in a referral teaching
hospital, Mashhad, Iran. Iran. J. Pharm. Res. (2019)
18: 488-95.
Yu R, Wang Y, Ma Y, Bai SQGW and Li S. Role of
ERCC1 and ERCC2 genetic polymorphisms in the
sensitivity of esophageal squamous cell carcinoma
to radiochemotherapy in a Chinese population. Int. J.
Clin. Exp. Pathol. (2017) 10: 1340-7.
Mo J, Luo M, Cui J and Zhou S. Prognostic value
of ERCC1 and ERCC2 gene polymorphisms in
patients with gastric cancer receiving platinum-based
chemotherapy. Int. J. Clin. Exp. Pathol. (2015) 8:
15065-71.
Chang PMH, Tzeng CH, Chen PM, Lin JK, Lin
TC, Chen WS, Jiang JK, Wang HS and Wang WS.
ERCC1 codon 118 C→ T polymorphism associated
with ERCC1 expression and outcome of FOLFOX‐4
treatment in Asian patients with metastatic colorectal
carcinoma. Cancer Sci. (2009) 100: 278-83.
Kamikozuru H, Kuramochi H, Hayashi K, Nakajima G
and Yamamoto M. ERCC1 codon 118 polymorphism is
a useful prognostic marker in patients with pancreatic
cancer treated with platinum-based chemotherapy. Int.
J. Oncol. (2008) 32: 1091-6.
Park D, Zhang W, Stoehlmacher J, Tsao Wei D,
Groshen S, Gil J, Yun J, Sones E, Mallik N and
Lenz H. ERCC1 gene polymorphism as a predictor
for clinical outcome in advanced colorectal cancer
patients treated with platinum-based chemotherapy.
Clin. Adv. Hematol. Oncol. (2003) 1: 162-6.
Yueh TC, Chou AK, Gong CL, Fu CK, Pei JS, Wu
MH, Tsai CW, Chang WS, Hsiao CL and Yen ST. The
contribution of excision repair cross-complementing
group 1 genotypes to colorectal cancer susceptibility
in Taiwan. Anticancer Res. (2017) 37: 2307-13.
Su D, Ma S, Liu P, Jiang Z, Lv W, Zhang Y, Deng
Q, Smith S and Yu H. Genetic polymorphisms and
treatment response in advanced non-small cell lung
cancer. Lung Cancer (2007) 56: 281-8.
Zhou W, Gurubhagavatula S, Liu G, Park S, Neuberg
DS, Wain JC, Lynch TJ, Su L and Christiani DC.
Excision repair cross-complementation group 1
polymorphism predicts overall survival in advanced
non-small cell lung cancer patients treated with
platinum-based chemotherapy. Clin. Cancer Res.
(2004) 10: 4939-43.
Ruzzo A, Graziano F, Kawakami K, Watanabe G,
Santini D, Catalano V, Bisonni R, Canestrari E, Ficarelli
R and Menichetti ET. Pharmacogenetic profiling and
clinical outcome of patients with advanced gastric
cancer treated with palliative chemotherapy. J. Clin.
Oncol. (2006) 24: 1883-91.
Ruzzo A, Graziano F, Loupakis F, Rulli E, Canestrari
E, Santini D, Catalano V, Ficarelli R, Maltese P
and Bisonni R. Pharmacogenetic profiling in patients
with advanced colorectal cancer treated with first-line
FOLFOX-4 chemotherapy. J. Clin. Oncol. (2007) 25:
1247-54.
Stoehlmacher J, Park D, Zhang W, Yang D,
Groshen S, Zahedy S and Lenz H. A multivariate
analysis of genomic polymorphisms: prediction of
clinical outcome to 5-FU/oxaliplatin combination
chemotherapy in refractory colorectal cancer. Br. J.
Cancer. (2004) 91: 344-54.
Huang ZH, Hua D, Du X, Li LH, Mao Y, Liu ZH,
Song MX and Zhou XK. ERCC1 polymorphism,
expression and clinical outcome of oxaliplatin-based
adjuvant chemotherapy in gastric cancer. World J.
Gastroenterol. (2008) 14: 6401-7.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J,
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(23)
(24)
(25)
(26)
(27)
(28)
(29)
(30)
(31)
(32)
(33)
(34)
ERCC1 Polymorphisms and Response to Platinum-based Chemotherapy
2171
chemotherapy. J. Clin. Oncol. (1998) 16: 309-16.
Warnecke Eberz U, Vallböhmer D, Alakus H, Kütting
F, Lurje G, Bollschweiler E, Wienand Dorweiler A,
Drebber U, Hölscher AH and Metzger R. ERCC1
and XRCC1 gene polymorphisms predict response to
neoadjuvant radiochemotherapy in esophageal cancer.
J. Gastrointest. Surg. (2009) 13: 1411-21.
Gardiner SJ and Begg EJ. Pharmacogenetics,
drug-metabolizing enzymes, and clinical practice.
Pharmacol. Rev. (2006) 58: 521-90.
Gajjar KK, Yadav DK, Kobawala TP, Trivedi TI, Vora
HH and Ghosh NR. ERCC1 expression in patients with
colorectal cancer: a pilot study. J. Cancer Metastasis
Treat. (2016) 2: 471-6.
Yun J, Kim KM, Kim ST, Kim JH, Kim JA, Kong JH,
Lee SH, Won YW, Sun JM and Lee J. Predictive value
of the ERCC1 expression for treatment response and
survival in advanced gastric cancer patients receiving
cisplatin-based first-line chemotherapy. Cancer Res.
Treat. (2010) 42: 101-6.
Liu Y, Ling Y, Zhang Y and Liu B. Predictive values of
platinum-related gene polymorphisms in gastric cancer
patients on oxaliplatin-based adjuvant chemotherapy.
Zhonghua Yi Xue Za Zhi (2011) 91: 256-9.
Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M,
van Oosterom AT and Christian MC. New guidelines
to evaluate the response to treatment in solid tumors.
J. Natl. Cancer Inst. (2000) 92: 205-16.
Yu J, Lee K, Mu C, Li Q, Abernathy T, Bostick Bruton
F and Reed E. Comparison of two human ovarian
carcinoma cell lines (A2780/CP70 and MCAS) that
are equally resistant to platinum, but differ at codon
118 of the ERCC1 gene. Int. J. Oncol. (2000) 16:
555-60.
Yu JJ, Mu C, Lee KB, Okamoto A, Reed EL, Bostick
Bruton F, Mitchell KC and Reed E. A nucleotide
polymorphism in ERCC1 in human ovarian cancer cell
lines and tumor tissues. Mutat. Res. (1997) 382: 13-20.
Dabholkar M, Vionnet J, Bostick Bruton F, Yu JJ and
Reed E. Messenger RNA levels of XPAC and ERCC1
in ovarian cancer tissue correlate with response to
platinum-based chemotherapy. J. Clin. Invest. (1994)
94: 703-8.
Metzger R, Leichman CG, Danenberg KD, Danenberg
PV, Lenz HJ, Hayashi K, Groshen S, Salonga D, Cohen
H and Laine L. ERCC1 mRNA levels complement
thymidylate synthase mRNA levels in predicting
response and survival for gastric cancer patients
receiving combination cisplatin and fluorouracil
(35)
(36)
(37)
(38)
(39)
(40)
(41)
(42)
(43)