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

Shin Yup Lee; Hyo Gyoung Kang; Seung Soo Yoo; Ye Rim Kang; Yi Young Choi; Won Kee Lee; Jin Eun Choi; Hyo Sung Jeon; Kyung Min Shin; In Jae Oh; Kyu Sik Kim; Jaehee Lee; Seung Ick Cha; Chang Ho Kim; Young Chul Kim; Jae Yong Park

doi:10.1016/j.lungcan.2013.07.024

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

Shin Yup Lee, Hyo Gyoung Kang, Seung Soo Yoo, Ye Rim Kang, Yi Young Choi, Won Kee Lee, Jin Eun Choi, Hyo Sung Jeon, Kyung Min Shin, In Jae Oh, Kyu Sik Kim, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Young Chul Kim, Jae Yong Park

Department of Medicine

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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.

Original language	English
Pages (from-to)	330-339
Number of pages	10
Journal	Lung Cancer
Volume	82
Issue number	2
DOIs	https://doi.org/10.1016/j.lungcan.2013.07.024
State	Published - Nov 2013

Keywords

Chemotherapy
DNA repair and apoptosis genes
Lung cancer
Response
Survival

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.lungcan.2013.07.024

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Lee, S. Y., Kang, H. G., Yoo, S. S., Kang, Y. R., Choi, Y. Y., Lee, W. K., Choi, J. E., Jeon, H. S., Shin, K. M., Oh, I. J., Kim, K. S., Lee, J., Cha, S. I., Kim, C. H., Kim, Y. C., & Park, J. Y. (2013). 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. Lung Cancer, 82(2), 330-339. https://doi.org/10.1016/j.lungcan.2013.07.024

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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 (Ptrend=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.",

keywords = "Chemotherapy, DNA repair and apoptosis genes, Lung cancer, Response, Survival",

author = "Lee, {Shin Yup} and Kang, {Hyo Gyoung} and Yoo, {Seung Soo} and Kang, {Ye Rim} and Choi, {Yi Young} and Lee, {Won Kee} and Choi, {Jin Eun} and Jeon, {Hyo Sung} and Shin, {Kyung Min} and Oh, {In Jae} and Kim, {Kyu Sik} and Jaehee Lee and Cha, {Seung Ick} and Kim, {Chang Ho} and Kim, {Young Chul} and Park, {Jae Yong}",

year = "2013",

month = nov,

doi = "10.1016/j.lungcan.2013.07.024",

language = "English",

volume = "82",

pages = "330--339",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

number = "2",

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Lee, SY, Kang, HG, Yoo, SS, Kang, YR, Choi, YY, Lee, WK, Choi, JE, Jeon, HS, Shin, KM, Oh, IJ, Kim, KS, Lee, J, Cha, SI, Kim, CH, Kim, YC & Park, JY 2013, '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', Lung Cancer, vol. 82, no. 2, pp. 330-339. https://doi.org/10.1016/j.lungcan.2013.07.024

TY - JOUR

T1 - 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

AU - Lee, Shin Yup

AU - Kang, Hyo Gyoung

AU - Yoo, Seung Soo

AU - Kang, Ye Rim

AU - Choi, Yi Young

AU - Lee, Won Kee

AU - Choi, Jin Eun

AU - Jeon, Hyo Sung

AU - Shin, Kyung Min

AU - Oh, In Jae

AU - Kim, Kyu Sik

AU - Lee, Jaehee

AU - Cha, Seung Ick

AU - Kim, Chang Ho

AU - Kim, Young Chul

AU - Park, Jae Yong

PY - 2013/11

Y1 - 2013/11

N2 - 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 (Ptrend=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.

AB - 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 (Ptrend=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.

KW - Chemotherapy

KW - DNA repair and apoptosis genes

KW - Lung cancer

KW - Response

KW - Survival

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U2 - 10.1016/j.lungcan.2013.07.024

DO - 10.1016/j.lungcan.2013.07.024

M3 - Article

C2 - 23973201

AN - SCOPUS:84887024766

SN - 0169-5002

VL - 82

SP - 330

EP - 339

JO - Lung Cancer

JF - Lung Cancer

IS - 2

ER -

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

Keywords

UN SDGs

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