Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer

Sook Kyung Do; Sun Ha Choi; Shin Yup Lee; Jin Eun Choi; Hyo Gyoung Kang; Mi Jeong Hong; Ji Hyun Kim; Sun Ah Baek; Jang Hyuck Lee; Won Kee Lee; Young Woo Do; Eung Bae Lee; Kyung Min Shin; Ji Yun Jeong; Yong Hoon Lee; Hyewon Seo; Seung Soo Yoo; Jaehee Lee; Seung Ick Cha; Chang Ho Kim; Yangki Seok; Sukki Cho; Sanghoon Jheon; Jae Yong Park

doi:10.1159/000509658

Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer

Sook Kyung Do, Sun Ha Choi, Shin Yup Lee, Jin Eun Choi, Hyo Gyoung Kang, Mi Jeong Hong, Ji Hyun Kim, Sun Ah Baek, Jang Hyuck Lee, Won Kee Lee, Young Woo Do, Eung Bae Lee, Kyung Min Shin, Ji Yun Jeong, Yong Hoon Lee, Hyewon Seo, Seung Soo Yoo, Jaehee Lee, Seung Ick Cha, Chang Ho KimYangki Seok, Sukki Cho, Sanghoon Jheon, Jae Yong Park

Department of Medicine

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

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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.

Original language	English
Pages (from-to)	897-904
Number of pages	8
Journal	Oncology
Volume	98
Issue number	12
DOIs	https://doi.org/10.1159/000509658
State	Published - Nov 2020

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10.1159/000509658

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Do, S. K., Choi, S. H., Lee, S. Y., Choi, J. E., Kang, H. G., Hong, M. J., Kim, J. H., Baek, S. A., Lee, J. H., Lee, W. K., Do, Y. W., Lee, E. B., Shin, K. M., Jeong, J. Y., Lee, Y. H., Seo, H., Yoo, S. S., Lee, J., Cha, S. I., ... Park, J. Y. (2020). Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer. Oncology, 98(12), 897-904. https://doi.org/10.1159/000509658

@article{9b8de4bd7d384d258bd3a0f941d6a14f,

title = "Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer",

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.",

author = "Do, {Sook Kyung} and Choi, {Sun Ha} and Lee, {Shin Yup} and Choi, {Jin Eun} and Kang, {Hyo Gyoung} and Hong, {Mi Jeong} and Kim, {Ji Hyun} and Baek, {Sun Ah} and Lee, {Jang Hyuck} and Lee, {Won Kee} and Do, {Young Woo} and Lee, {Eung Bae} and Shin, {Kyung Min} and Jeong, {Ji Yun} and Lee, {Yong Hoon} and Hyewon Seo and Yoo, {Seung Soo} and Jaehee Lee and Cha, {Seung Ick} and Kim, {Chang Ho} and Yangki Seok and Sukki Cho and Sanghoon Jheon and Park, {Jae Yong}",

year = "2020",

month = nov,

doi = "10.1159/000509658",

language = "English",

volume = "98",

pages = "897--904",

journal = "Oncology",

issn = "0030-2414",

publisher = "S. Karger AG",

number = "12",

}

Do, SK, Choi, SH, Lee, SY, Choi, JE, Kang, HG, Hong, MJ, Kim, JH, Baek, SA, Lee, JH, Lee, WK, Do, YW, Lee, EB, Shin, KM, Jeong, JY, Lee, YH, Seo, H, Yoo, SS, Lee, J, Cha, SI, Kim, CH, Seok, Y, Cho, S, Jheon, S & Park, JY 2020, 'Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer', Oncology, vol. 98, no. 12, pp. 897-904. https://doi.org/10.1159/000509658

TY - JOUR

T1 - Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer

AU - Do, Sook Kyung

AU - Choi, Sun Ha

AU - Lee, Shin Yup

AU - Choi, Jin Eun

AU - Kang, Hyo Gyoung

AU - Hong, Mi Jeong

AU - Kim, Ji Hyun

AU - Baek, Sun Ah

AU - Lee, Jang Hyuck

AU - Lee, Won Kee

AU - Do, Young Woo

AU - Lee, Eung Bae

AU - Shin, Kyung Min

AU - Jeong, Ji Yun

AU - Lee, Yong Hoon

AU - Seo, Hyewon

AU - Yoo, Seung Soo

AU - Lee, Jaehee

AU - Cha, Seung Ick

AU - Kim, Chang Ho

AU - Seok, Yangki

AU - Cho, Sukki

AU - Jheon, Sanghoon

AU - Park, Jae Yong

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85090167321&partnerID=8YFLogxK

U2 - 10.1159/000509658

DO - 10.1159/000509658

M3 - Article

C2 - 32791502

AN - SCOPUS:85090167321

SN - 0030-2414

VL - 98

SP - 897

EP - 904

JO - Oncology

JF - Oncology

IS - 12

ER -

Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer

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