WISP1 polymorphisms contribute to platinum-based chemotherapy toxicity in lung cancer patients.

Juan Chen,Honghao Zhou,Xiangping Li,Ling Xiao,Zhaoqian Liu,Zhan Wang,Chenyue Qian,Jiye Yin,Yi Zheng,Wei Zhang,Ting Zou,Junyan Liu,Ying Wang

doi:10.3390/ijms151121011

Abstract

Platinum-based chemotherapy toxicity is always one of the serious problems from which lung cancer patients suffer. The genetic polymorphism of WISP1 was revealed to be associated with susceptibility and platinum-based chemotherapy response in our previous studies. In this study, we aimed to investigate the relationship of WISP1 genetic polymorphisms with platinum-based chemotherapy toxicity in lung cancer patients. A total of 412 lung cancer patients were enrolled in this study, and 28 polymorphisms of the WISP1 gene were genotyped by SequenomMassARRAY. We found that WISP1 polymorphisms (rs2929965, rs2929969, rs2929970, rs2929973 and rs754958) were related to the overall chemotherapy toxicity of lung cancer in subgroup analyses. Rs16904853, rs2929970, rs2977549 and rs2977551 (p = 0.021, 0.028, 0.024, 0.048, respectively) polymorphisms were significantly associated with hematologic toxicity. Rs2929946, rs2929970, rs2977519, rs2977536, rs3739262 and rs754958 (p = 0.031, 0.046, 0.029, 0.016, 0.042, 0.035, respectively) polymorphisms were significantly associated with the gastrointestinal toxicity of lung cancer. Genotypes of WISP1 may be novel and useful biomarkers for predicting platinum-based chemotherapy toxicity in lung cancer patients.

Highlights

In recent years, lung cancer has become the highest morbidity and mortality cancer among cancers in the world [1]
We examined the relationship of WISP1 polymorphisms and platinum-based chemotherapy toxicity in Chinese lung cancer patients
WISP1 is a downstream gene of the canonical Wnt-β-catenin pathway, and its mutations were reported to be associated with multiple diseases, including asthma, hypertension and spinal osteoarthritis [18,25,26]

Summary

Introduction

Lung cancer has become the highest morbidity and mortality cancer among cancers in the world [1]. It consists of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Most lung cancer patients were diagnosed at advance stages. They were not suitable for surgery, and chemotherapy was the best choice for them. Chemotherapy resistance and toxicity are still serious problems from which lung cancer patients suffer. It was reported that chemotherapy efficacy and toxicity were related to many genes in multiple pathways, such as DNA repair, apoptosis, transportation, as well as the Wnt pathway [3,4,5,6,7].

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