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Genome-wide Association Study of Survival in Early-stage Non-Small Cell Lung Cancer

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths all over the world. Studies have indicated that molecular biomarkers, including genetic variants, may provide additional values for the targeted treatments and clinical outcomes of NSCLC patients. To better understand the effects of molecular biomarkers on the treatment of NSCLC, we conducted a genome-wide analysis to investigate the prognostic implications of genetic variants in early-stage NSCLC patients with surgery.

Methods

A genome wide scan of 906,703 single-nucleotide polymorphisms (SNPs) was conducted in a cohort with 365 early-stage NSCLC patients with surgery, followed by a fast-track replication in another independent cohort of 327 NSCLC patients from Nanjing, China. Cox models were used to screen and validate significant SNPs associated with the overall survival of early-stage NSCLC patients.

Results

We found that rs10023113 in calcium/calmodulin-dependent protein kinase II delta (CAMK2D) was consistently associated with survival of early-stage NSCLC in the GWAS scan and the replication cohort [GWAS scan: hazard ratio (HR) 2.84; 95 % confidence interval (CI) 1.90–4.23, P = 1.29 × 10−6; replication cohort: HR 2.19, 95 % CI 1.15–4.21, P = 1.80 × 10−2]. When combining all the patients, the results showed that the variant allele of rs10023113 was significantly associated with poor prognosis of early-stage NSCLC with P value of 3.40 × 10−7 (HR 2.30, 95 % CI 1.67–3.17).

Conclusions

These findings suggest that CAMK2D rs10023113 may be a potentially prognostic marker for overall survival of early-stage NSCLC patients in Chinese population.

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Source of Funding

This work is funded by the National Natural Science Foundation of China (81270044 and 81230067), National Outstanding Youth Science Foundation of China (81225020), Science Foundation for Distinguished Young Scholars of Jiangsu (BK2012042), Key Grant of Natural Science Foundation of Jiangsu Higher Education Institutions (11KJA330001), Natural Science Foundation of Jiangsu Province (BK2012042), New Century Excellent Talents in University (NCET-10-0178), Changjiang Scholars and Innovative Research Team in University (IRT0631), National Program for Support of Top-notch Young Professionals from the Organization Department of the CPC Central Committee, Jiangsu Province Clinical Science and Technology Projects (BL2012008), Collaborative Innovation Center For Cancer Personalized Medicine in Jiangsu Province and Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Disclosure

The authors declare no commercial interest and financial or material support.

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics and Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China

    Shaowen Tang MD, PhD, Yun Pan MD, Lingmin Hu MD, PhD, Songyu Cao MS, Minjie Chu MD, Juncheng Dai MD, PhD, Jiaping Chen MS, Guangfu Jin MD, PhD, Zhibin Hu MD, PhD, Hongxia Ma MD, PhD & Hongbing Shen MD, PhD

  2. Department of Respiratory Diseases, Nanjing Thoracic Hospital, Nanjing, China

    Yi Wang MD

  3. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Yongqian Shu MD, PhD

  4. Department of Thoracic Surgery, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China

    Lin Xu MD, PhD

  5. State Key Laboratory of Reproductive Medicine and Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China

    Zhibin Hu MD, PhD & Hongbing Shen MD, PhD

Authors
  1. Shaowen Tang MD, PhD
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  2. Yun Pan MD
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  3. Yi Wang MD
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  4. Lingmin Hu MD, PhD
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  5. Songyu Cao MS
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  6. Minjie Chu MD
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  7. Juncheng Dai MD, PhD
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  8. Yongqian Shu MD, PhD
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  9. Lin Xu MD, PhD
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  10. Jiaping Chen MS
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  11. Guangfu Jin MD, PhD
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  12. Zhibin Hu MD, PhD
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  13. Hongxia Ma MD, PhD
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  14. Hongbing Shen MD, PhD
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Corresponding authors

Correspondence to Hongxia Ma MD, PhD or Hongbing Shen MD, PhD.

Additional information

Shaowen Tang, Yun Pan and Yi Wang contributed equally to this work.

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Tang, S., Pan, Y., Wang, Y. et al. Genome-wide Association Study of Survival in Early-stage Non-Small Cell Lung Cancer. Ann Surg Oncol 22, 630–635 (2015). https://doi.org/10.1245/s10434-014-3983-0

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  • DOI: https://doi.org/10.1245/s10434-014-3983-0

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