Association of positively selected eIF3a polymorphisms with toxicity of platinum-based chemotherapy in NSCLC patients.
OBJECTIVE
Eukaryotic translation initiation factor 3 subunit A (eIF3a) plays critical roles in regulating the initiation of protein translation, and eIF3a is highly expressed in lung cancer. In this study, we investigated the association of the positively selected SNPs of eIF3a with the response to and toxicity of platinum-based chemotherapy in Chinese patients with non-small cell lung cancer (NSCLC).


METHODS
SNP data for eIF3a locus were downloaded from HapMap database. For each SNP, haplotype, LD profile and population differentiation were analyzed. The long-range haplotype (LRH) test was employed to identify positively selected SNPs of eIF3a. A total of 325 NSCLC patients were enrolled and genotyped for these SNPs.


RESULTS
Five positively selected (rs1409314, rs4752219, rs4752220, rs7091672 and rs10510050) and 5 non-positively selected SNPs (rs10886342, rs11198804, rs2275112, rs10787899 and rs4752269) were identified in the LRH test. However, none of them was correlated with the platinum-based chemotherapy response. In contrast, 4 of the positively selected SNPs (rs1409314, rs4752219, rs4752220 and rs7091672) were significantly correlated with the toxicities tested (neutropenia, anemia, thrombocytopenia, emesis and hepatotoxicity). In addition, rs10510050 was significantly correlated with thrombocytopenia, emesis and hepatotoxicity. None of the 5 non-positively selected SNPs was correlated with the 5 toxicities.


CONCLUSIONS
The positively selected SNPs of eIF3a are significantly correlated with platinum-based chemotherapy toxicities in Chinese NSCLC patients.
1] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University [2] Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China [3] Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
Ji-ye
JY
Yin
Laboratory of Cardiovascular Disease and Drug Research, Zhengzhou No 7 People's Hospital, Zhengzhou 450016, China.
Xiang-guang
XG
Meng
1] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University [2] Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China [3] Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
Chen-yue
CY
Qian
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China.
Xiang-ping
XP
Li
1] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University [2] Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China [3] Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
Juan
J
Chen
1] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University [2] Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China [3] Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
Yi
Y
Zheng
1] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University [2] Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China [3] Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
Rong
R
Liu
1] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University [2] Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China [3] Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
Hong-hao
HH
Zhou
1] Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University [2] Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China [3] Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
Zhao-qian
ZQ
Liu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000235:genetics*; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D010597:Pharmacogenetics; D010641:Phenotype; D017671:Platinum Compounds / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016896:Treatment Outcome
C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3; D009944:Organoplatinum Compounds; D017671:Platinum Compounds