title: Genetic variations in the regulator of G-protein signaling genes are associated with survival in late-stage non-small cell lung cancer.
abstract: The regulator of G-protein signaling (RGS) pathway plays an important role in signaling transduction, cellular activities, and carcinogenesis. We hypothesized that genetic variations in RGS gene family may be associated with the response of late-stage non-small cell lung cancer (NSCLC) patients to chemotherapy or chemoradiotherapy. We selected 95 tagging single nucleotide polymorphisms (SNPs) in 17 RGS genes and genotyped them in 598 late-stage NSCLC patients. Thirteen SNPs were significantly associated with overall survival. Among them, rs2749786 of RGS12 was most significant. Stratified analysis by chemotherapy or chemoradiation further identified SNPs that were associated with overall survival in subgroups. Rs2816312 of RGS1 and rs6689169 of RGS7 were most significant in chemotherapy group and chemoradiotherapy group, respectively. A significant cumulative effect was observed when these SNPs were combined. Survival tree analyses identified potential interactions between rs944343, rs2816312, and rs1122794 in affecting survival time in patients treated with chemotherapy, while the genotype of rs6429264 affected survival in chemoradiation-treated patients. To our knowledge, this is the first study to reveal the importance of RGS gene family in the survival of late-stage NSCLC patients.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Dai
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Charles
authors.initials: C
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: David
authors.initials: D
authors.lastname: Stewart
authors.forename: David
authors.initials: D
authors.lastname: Chang
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011878:Radiotherapy; D015398:Signal Transduction / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D019204:GTP-Binding Proteins