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Gene. 2018 Mar 10;646:56-63. doi: 10.1016/j.gene.2017.12.055. Epub 2017 Dec 29.

Regulatory variants in cancer-related pathway genes predict survival of patients with surgically resected non-small cell lung cancer.

Author information

1
Department of Radiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
2
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
3
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
4
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
5
Biostatistics, Medical Research Collaboration Center in Kyungpook National University Hospital and Kyungpook National University School of Medicine, Daegu, Korea.
6
Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea; Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
7
Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
8
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
9
Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
10
Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
11
Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea.
12
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: jaeyong@knu.ac.kr.

Abstract

BACKGROUND:

We conducted this study to identify genetic variants in cancer-related pathway genes which can predict prognosis of NSCLC patients after surgery, using a comprehensive list of regulatory single nucleotide polymorphisms (SNPs) prioritized by RegulomeDB.

METHOD:

A total of 509 potentially functional SNPs in cancer-related pathway genes selected from RegulomeDB were evaluated. These SNPs were analyzed in a discovery set (n=354), and a replication study was performed in an independent set (n=772). The association of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed.

RESULTS:

In the discovery set, 76 SNPs were significantly associated with OS or DFS. Among the 76 SNPs, the association was consistently observed for 5 SNPs (ERCC1 rs2298881C>A, BRCA2 rs3092989G>A, NELFE rs440454C>T, PPP2R4 rs2541164G>A, and LTBP4 rs3786527G>A) in the validation set. In combined analysis, ERCC1 rs2298881C>A, BRCA2 rs3092989, NELFE rs440454C>T, and PPP2R4 rs2541164G>A were significantly associated with OS and DFS (adjusted HR ·aHR· for OS=1.46, 0.62, 078, and 0.76, respectively; P=0.003, 0.002, 0.007, and 0.003 respectively; and aHR for DFS=1.27, 0.69, 0.86, and 0.82, respectively; P=0.02, 0.002, 0.03, and 0.008, respectively). The LTBP4 rs3786527G>A was significantly associated with better OS (aHR=0.75; P=0.003).

CONCLUSION:

Our results suggest that five SNPs in the cancer-related pathway genes may be useful for the prediction of the prognosis in patients with surgically resected NSCLC.

KEYWORDS:

Lung cancer; Polymorphism; RegulomeDB; Survival

PMID:
29289609
DOI:
10.1016/j.gene.2017.12.055
[Indexed for MEDLINE]

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