title: Polymorphisms in DNA repair and apoptosis-related genes and clinical outcomes of patients with non-small cell lung cancer treated with first-line paclitaxel-cisplatin chemotherapy.
abstract: This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNPs) in genes in DNA repair and apoptosis pathways and determine the relationship between polymorphisms and treatment outcomes of patients with non-small cell lung cancer (NSCLC) treated with first-line paclitaxel-cisplatin chemotherapy. Three hundred eighty two patients with NSCLC were enrolled. Seventy-four SNPs in 48 genes (42 SNPs in 27 DNA repair pathway genes and 32 SNPs in 21 apoptotic pathway genes) were genotyped and their associations with chemotherapy response and overall survival (OS) were analyzed. Among SNPs in DNA repair genes, BRCA1 rs799917 was significantly associated with both chemotherapy response and OS. XRCC1 rs25487 exhibited a significant association with chemotherapy response and ERCC2 rs1052555 with OS. Four SNPs in apoptotic genes (TNFRSF1B rs1061624, BCL2 rs2279115, BIRC5 rs9904341, and CASP8 rs3769818) were significantly associated with OS, but not with response to chemotherapy. When the six SNPs which were associated with OS in individual analysis were combined, OS decreased as the number of bad genotypes increased (P(trend) = 2 × 10(-6)). Patients with 3, and 4-6 bad genotypes had significantly worse OS compared with those carrying 0-2 bad genotypes (adjusted hazard ratio [aHR] = 1.54, 95% CI = 1.14-2.08, P = 0.005; aHR = 2.10, 95% CI = 1.55-2.85, P = 2 × 10(-6), respectively). In conclusion, these findings suggest that the six SNPs identified, particularly their combined genotypes, could be used as biomarkers predicting chemotherapy response and survival of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy.
authors: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.
authors: Shin Yup
authors: SY
authors: Lee
authors: Hyo-Gyoung
authors: HG
authors: Kang
authors: Seung Soo
authors: SS
authors: Yoo
authors: Ye Rim
authors: YR
authors: Kang
authors: Yi Young
authors: YY
authors: Choi
authors: Won Kee
authors: WK
authors: Lee
authors: Jin Eun
authors: JE
authors: Choi
authors: Hyo-Sung
authors: HS
authors: Jeon
authors: Kyung Min
authors: KM
authors: Shin
authors: In Jae
authors: IJ
authors: Oh
authors: Kyu Sik
authors: KS
authors: Kim
authors: Jaehee
authors: J
authors: Lee
authors: Seung Ick
authors: SI
authors: Cha
authors: Chang Ho
authors: CH
authors: Kim
authors: Young Chul
authors: YC
authors: Kim
authors: Jae Yong
authors: JY
authors: Park
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D017239:Paclitaxel; D002945:Cisplatin
keywords: Chemotherapy; DNA repair and apoptosis genes; Lung cancer; Response; Survival