TY - JOUR
T1 - Prognostic implications of genetic variants in advanced non-small cell lung cancer
T2 - A genome-wide association study
AU - Lee, Youngjoo
AU - Yoon, Kyong Ah
AU - Joo, Jungnam
AU - Lee, Donghoon
AU - Bae, Kieun
AU - Han, Ji Youn
AU - Lee, Jin Soo
N1 - Funding Information:
National Cancer Center Research Grant (1010041).
Funding Information:
We previously conducted a GWAS to identify susceptibility loci for NSCLC in the Korean population (12). Among the 621 patients who were genome-wide screened in that study, we selected 348 subjects for the current analysis by excluding patients with stages I–III disease (n = 198), those not receiving systemic chemotherapy (n = 28), those who received prior curative surgery or other therapy (n = 11) and those without available follow-up survival data available (n = 36) (Supplementary Figure 1, available at Carcinogenesis Online). Subsequently, we reviewed patient’s medical records and radiographic images to assess demographic and clinicopathological characteristics, chemotherapy regimens, tumor response and survival outcomes using a predesigned data collection format. This study was approved by the Institutional Review Board of the National Cancer Center (Goyang, Korea).
PY - 2013/2
Y1 - 2013/2
N2 - The prognostic significance of inherited genetic variants in advanced-stage non-small cell lung cancer (NSCLC) patients remains unknown. In this study, we genotyped 271 817 singlenucleotide polymorphisms in 348 advanced NSCLC patients who received chemotherapy and analyzed their association with prognosis by using Cox proportional hazard regression model adjusted for known prognostic factors. Top candidate singlenucleotide polymorphisms (SNPs) were selected using the bootstrap re-sampling procedure. Median age of patient population was 56 years. Proportions of female, never smokers and adenocarcinoma were 64.9, 67.5 and 80.4%, respectively. We identified 17 top candidate SNPs related to prognosis using cut-off minimum P value of<5.0× 10-5 in at least 70% of 1000 bootstrap samples. These SNPs were located in the genomic regions of the FAM154A, ANKS1A, DLST, THSD7B, NCOA2, CDH8, SLC35D2, NALCN and EGF genes. The most significant SNP, rs1571228 (9p22.1:FAM154A), was significantly associated with overall survival in dominant model [AG+GG to AA, hazard ratio (HR) of death (95% CI)= 0.53 (0.42-0.67); P= 2.025× 10-7]. The SNP at 4q25:EGF, rs11098063, for which some genetic variations was previously reported to be associated with prognosis, also showed significant association with overall survival in additive model [CC versus CT versus TT, HR (95% CI)= 1.00 versus 0.61 (0.47-0.78) versus 0.39 (0.19-0.79); P= 9.582× 10-6]. Survival differences according to the genotype of these SNPs were independent of sex, smoking, histology and chemotherapy regimens. These results suggested the variants at multiple genetic loci might contribute to the risk of death in advanced NSCLC patients receiving chemotherapy.
AB - The prognostic significance of inherited genetic variants in advanced-stage non-small cell lung cancer (NSCLC) patients remains unknown. In this study, we genotyped 271 817 singlenucleotide polymorphisms in 348 advanced NSCLC patients who received chemotherapy and analyzed their association with prognosis by using Cox proportional hazard regression model adjusted for known prognostic factors. Top candidate singlenucleotide polymorphisms (SNPs) were selected using the bootstrap re-sampling procedure. Median age of patient population was 56 years. Proportions of female, never smokers and adenocarcinoma were 64.9, 67.5 and 80.4%, respectively. We identified 17 top candidate SNPs related to prognosis using cut-off minimum P value of<5.0× 10-5 in at least 70% of 1000 bootstrap samples. These SNPs were located in the genomic regions of the FAM154A, ANKS1A, DLST, THSD7B, NCOA2, CDH8, SLC35D2, NALCN and EGF genes. The most significant SNP, rs1571228 (9p22.1:FAM154A), was significantly associated with overall survival in dominant model [AG+GG to AA, hazard ratio (HR) of death (95% CI)= 0.53 (0.42-0.67); P= 2.025× 10-7]. The SNP at 4q25:EGF, rs11098063, for which some genetic variations was previously reported to be associated with prognosis, also showed significant association with overall survival in additive model [CC versus CT versus TT, HR (95% CI)= 1.00 versus 0.61 (0.47-0.78) versus 0.39 (0.19-0.79); P= 9.582× 10-6]. Survival differences according to the genotype of these SNPs were independent of sex, smoking, histology and chemotherapy regimens. These results suggested the variants at multiple genetic loci might contribute to the risk of death in advanced NSCLC patients receiving chemotherapy.
UR - http://www.scopus.com/inward/record.url?scp=84873545064&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgs356
DO - 10.1093/carcin/bgs356
M3 - Article
AN - SCOPUS:84873545064
SN - 0143-3334
VL - 34
SP - 307
EP - 313
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -