自噬通路基因多态性与晚期非小细胞肺癌含铂化疗疗效的相关性分析

doi:10.16288/j.yczz.16-294

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Hereditas(Beijing) ›› 2017, Vol. 39 ›› Issue (3): 250-262.doi: 10.16288/j.yczz.16-294

• Research Articles • Previous Articles

Association between polymorphisms of autophagy pathway and responses in non-small cell lung cancer patients treated with platinum-based chemotherapy

Wang Shiming¹, Song Xiao^1,2, Zhao Xueying^1,3, Chen Hongyan¹, Wang Jiucun¹, Wu Junjie^{1, 6}, Gao Zhiqiang⁴, Qian Ji¹, Bai Chunxue⁵, Li Qiang⁶, Han Baohui⁴, Lu Daru¹

1. State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China;
2. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China;
3. Shanghai Key Laboratory of Crime Scene Evidence, Shanghai Research Institute of Criminal Science and Technology, Shanghai 200063, China;
4. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China;
5. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China;
6. Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai 200433, China

Received:2016-08-29 Revised:2016-09-06 Online:2017-03-20 Published:2016-11-15
Supported by:
Supported by the National Natural Science Foundation of China (Nos; 81372235, 31571371), and the National High Technology Research and Development Program( 863 Program) of China (No; 2012AA02A518)

Abstract

Abstract: Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (G>A) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.

Key words: autophagy, polymorphism, platinum-based chemotherapy, non-small cell lung cancer

Wang Shiming, Song Xiao, Zhao Xueying, Chen Hongyan, Wang Jiucun, Wu Junjie, Gao Zhiqiang, Qian Ji, Bai Chunxue, Li Qiang, Han Baohui, Lu Daru. Association between polymorphisms of autophagy pathway and responses in non-small cell lung cancer patients treated with platinum-based chemotherapy[J]. Hereditas(Beijing), 2017, 39(3): 250-262.

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Association between polymorphisms of autophagy pathway and responses in non-small cell lung cancer patients treated with platinum-based chemotherapy

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