Association between well-characterized lung cancer IncRNA polymorphisms and platinum-based chemotherapy toxicity in Chinese patients with lung cancer

• 来源期刊: 中国药理学报（英文版）
• 关键词: lung cancer platinum-based chemotherapy gastrointestinal toxicity hematological toxicity long non-coding RNA (IncRNA) polymorphism Chinese patients
• 年，卷（期）: 2017,（4）
• 页码范围: 581-590
• 页数: 10页
• 语种: 英文
• DOI: 10.1038/aps.2016.164

摘要

Platinum-based chemotherapy is the standard first-line treatment for most lung cancer patients.However,the toxicity induced by platinum-based chemotherapy greatly impedes its clinical use.Previous studies showed that long non-coding RNAs (IncRNAs) with over 200 nucleotides in length affect drug response and toxicity.In the present study,we investigated the association of wellcharacterized lung cancer IncRNA polymorphisms with platinum-based chemotherapy toxicity in Chinese patients with lung cancer.A total of 467 lung cancer patients treated with platinum-based chemotherapy for at least two cycles were recruited.We primarily focused on gastrointestinal and hematological toxicities.A total of 14 potentially functional polymorphisms within 8 IncRNAs (HOTTIP,HOTAIT,H19,ANRIL,CCAT2,MALAT1,MEG3,and POLR2E) were genotyped.Unconditional logistical regression analysis was conducted to assess the associations.Gene-gene and gene-environment interactions were identified using the software generalized multifactor dimensionality reduction (GMDR).ANRIL rs1333049 was associated with severe overall toxicity in an additive model (adjusted 0R=0.723,95％ CI=0.541-0.965,P=0.028).ANRIL rs1333049 was also associated with severe gastrointestinal toxicity in both the additive (adjusted 0R=0.690,95％ CI=0.489-0.974,P=0.035) and dominant (adjusted 0R=0.558,95％ CI=0.335-0.931,P=0.025) models.MEG3 rs116907618 was associated with severe gastrointestinal toxicity in an additive model (adjusted 0R=1.717,95％ CI=1.007-2.927,P=-0.047).GMDR identified the three-factor interaction model of POLR2E rs3787016-HOTTIP rs3807598-chemotherapy regimen as the best predictive model for hematological toxicity.In conclusion,ANRIL and MEG3 genetic polymorphisms are associated with severe platinum toxicity and could be considered as biomarkers for pretreatment evaluation in Chinese patients with lung cancer.