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MO24 - NSCLC - Chemotherapy III (ID 110)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
MO24.12 - Association between POLI polymorphism and severe gastrointestinal toxicity in non-small cell lung cancer patients in a Chinese population (ID 1087)
10:30 - 12:00 | Author(s): B. Han
POLI is one of the Y-family polymerases, which are considered as error-prone replicases with low fidelity and involved in translesion synthesis (TLS) pathway. Polymorphisms on POLI genes may affect efficiency of DNA damage tolerant repair, therefore affect the platinum-based chemotherapy tolerance in tumor tissue and maintain routine function of normal organs. Our study aimed to investigate the association of five SNPs of POLI at codon 731, 5’-upstream and 3’UTR with prognosis and severe toxicity in advanced NSCLC patients in eastern developed regions in China.
663 stage III-IV aNSCLC patients treated with first-line platinum-based chemotherapy were genotyped with MassARRY platform on the five polymorphisms.
p.731Ala (G of rs8305) indicated protective tendency from severe grade III-IV gastrointestinal toxicity in a dominant genetic model (adjusted odds ratio for Ala/Ala+Ala/Thr: 0.51, 95% confidence internal, 0.28-0.93； P for trend = 0.028). Stratified analysis revealed that the protective effect was rather for cisplatin- than carbonplatin-based regiments (adjusted OR for Ala/Ala+Ala/Thr: 0.38, 95% CI, 0.18-0.81； P for trend = 0.012). As linked loci of rs8305, rs3730668 on 5’-upstream and rs513543 on 3’-UTR of POLI performed similar protective tendency to gastrointestinal toxicity. No significant association was discovered for these five SNPs with other hematological toxicity, progress-free survival and overall survival. Both haplotype and diplotype analysis revealed consistent result as single polymorphism analysis. Haplotype “AAA” (in the order of rs3730668-rs8305-rs513543) indicated a significant susceptibility to gastrointestinal toxicity (adjusted OR: 1.92; 95% CI, 1.19-3.10; P = 0.007).
For the first time, our study indicated error-prone replicase POLI was associated with gastrointestinal toxicity in aNSCLC patients accepting first-line platinum-base chemotherapy, especially for cisplatin-based regiments.
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