Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients: A multicenter study from the international lung cancer consortium

Pawadee Lohavanichbutr, Lori C. Sakoda, Christopher I. Amos, Susanne M. Arnold, David C. Christiani, Michael P.A. Davies, John K. Field, Eric B. Haura, Rayjean J. Hung, Takashi Kohno, Maria Teresa Landi, Geoffrey Liu, Yi Liu, Michael W. Marcus, Grainne M. O'Kane, Matthew B. Schabath, Kouya Shiraishi, Stacey A. Slone, Adonina Tardón, Ping YangKazushi Yoshida, Ruyang Zhang, Xuchen Zong, Gary E. Goodman, Noel S. Weiss, Chu Chen

Research output: Contribution to journalArticle

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Abstract

Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients. Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan- Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95% confidence interval (CI): 1.08- 1.72, P= 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95% CI, 0.84- 1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95% CI, 0.61-1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190. Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors.

Original languageEnglish (US)
Pages (from-to)7550-7557
Number of pages8
JournalClinical Cancer Research
Volume23
Issue number24
DOIs
StatePublished - Dec 15 2017

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Small Cell Lung Carcinoma
Multicenter Studies
Lung Neoplasms
Survival
Genotype
Alleles
Topoisomerase Inhibitors
Confidence Intervals
Single Nucleotide Polymorphism
Encyclopedias
DNA Damage
Research Design
Regression Analysis
Mortality
DNA
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients : A multicenter study from the international lung cancer consortium. / Lohavanichbutr, Pawadee; Sakoda, Lori C.; Amos, Christopher I.; Arnold, Susanne M.; Christiani, David C.; Davies, Michael P.A.; Field, John K.; Haura, Eric B.; Hung, Rayjean J.; Kohno, Takashi; Landi, Maria Teresa; Liu, Geoffrey; Liu, Yi; Marcus, Michael W.; O'Kane, Grainne M.; Schabath, Matthew B.; Shiraishi, Kouya; Slone, Stacey A.; Tardón, Adonina; Yang, Ping; Yoshida, Kazushi; Zhang, Ruyang; Zong, Xuchen; Goodman, Gary E.; Weiss, Noel S.; Chen, Chu.

In: Clinical Cancer Research, Vol. 23, No. 24, 15.12.2017, p. 7550-7557.

Research output: Contribution to journalArticle

Lohavanichbutr, P, Sakoda, LC, Amos, CI, Arnold, SM, Christiani, DC, Davies, MPA, Field, JK, Haura, EB, Hung, RJ, Kohno, T, Landi, MT, Liu, G, Liu, Y, Marcus, MW, O'Kane, GM, Schabath, MB, Shiraishi, K, Slone, SA, Tardón, A, Yang, P, Yoshida, K, Zhang, R, Zong, X, Goodman, GE, Weiss, NS & Chen, C 2017, 'Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients: A multicenter study from the international lung cancer consortium', Clinical Cancer Research, vol. 23, no. 24, pp. 7550-7557. https://doi.org/10.1158/1078-0432.CCR-17-1401
Lohavanichbutr, Pawadee ; Sakoda, Lori C. ; Amos, Christopher I. ; Arnold, Susanne M. ; Christiani, David C. ; Davies, Michael P.A. ; Field, John K. ; Haura, Eric B. ; Hung, Rayjean J. ; Kohno, Takashi ; Landi, Maria Teresa ; Liu, Geoffrey ; Liu, Yi ; Marcus, Michael W. ; O'Kane, Grainne M. ; Schabath, Matthew B. ; Shiraishi, Kouya ; Slone, Stacey A. ; Tardón, Adonina ; Yang, Ping ; Yoshida, Kazushi ; Zhang, Ruyang ; Zong, Xuchen ; Goodman, Gary E. ; Weiss, Noel S. ; Chen, Chu. / Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients : A multicenter study from the international lung cancer consortium. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 24. pp. 7550-7557.
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abstract = "Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients. Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan- Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95{\%} confidence interval (CI): 1.08- 1.72, P= 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95{\%} CI, 0.84- 1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95{\%} CI, 0.61-1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190. Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors.",
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T1 - Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients

T2 - A multicenter study from the international lung cancer consortium

AU - Lohavanichbutr, Pawadee

AU - Sakoda, Lori C.

AU - Amos, Christopher I.

AU - Arnold, Susanne M.

AU - Christiani, David C.

AU - Davies, Michael P.A.

AU - Field, John K.

AU - Haura, Eric B.

AU - Hung, Rayjean J.

AU - Kohno, Takashi

AU - Landi, Maria Teresa

AU - Liu, Geoffrey

AU - Liu, Yi

AU - Marcus, Michael W.

AU - O'Kane, Grainne M.

AU - Schabath, Matthew B.

AU - Shiraishi, Kouya

AU - Slone, Stacey A.

AU - Tardón, Adonina

AU - Yang, Ping

AU - Yoshida, Kazushi

AU - Zhang, Ruyang

AU - Zong, Xuchen

AU - Goodman, Gary E.

AU - Weiss, Noel S.

AU - Chen, Chu

PY - 2017/12/15

Y1 - 2017/12/15

N2 - Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients. Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan- Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95% confidence interval (CI): 1.08- 1.72, P= 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95% CI, 0.84- 1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95% CI, 0.61-1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190. Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors.

AB - Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients. Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan- Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95% confidence interval (CI): 1.08- 1.72, P= 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95% CI, 0.84- 1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95% CI, 0.61-1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190. Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors.

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