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- Title
Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer.
- Authors
Do, Sook Kyung; Choi, Sun Ha; Lee, Shin Yup; Choi, Jin Eun; Kang, Hyo-Gyoung; Hong, Mi Jeong; Kim, Ji Hyun; Baek, Sun Ah; Lee, Jang Hyuck; Lee, Won Kee; Do, Young Woo; Lee, Eung Bae; Shin, Kyung Min; Jeong, Ji Yun; Lee, Yong Hoon; Seo, Hyewon; Yoo, Seung Soo; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho
- Abstract
Background: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC). Methods: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed. Results: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54–0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13–4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08–1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10–3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41–1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11–6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17–2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12–6.88, p = 0.03, respectively). Conclusions: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
- Subjects
LUNG cancer prognosis; CONFIDENCE intervals; GENETICS; METABOLISM; SQUAMOUS cell carcinoma; SURVIVAL analysis (Biometry); SINGLE nucleotide polymorphisms; GENOTYPES
- Publication
Oncology, 2020, Vol 98, Issue 12, p897
- ISSN
0030-2414
- Publication type
Article
- DOI
10.1159/000509658