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Prognostic significance of three endothelial nitric oxide synthase (eNOS) polymorphisms and metabolic syndrome (MetS) in patients with colorectal cancer

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Polymorphisms of endothelial nitric oxide synthases (eNOS) have been associated with cancer susceptibility. Also, metabolic syndrome is associated with cancer malignancy. However, the effect of eNOS polymorphisms and metabolic syndrome on colorectal cancer (CRC) prognosis remains unclear.


To investigated whether three genetic polymorphisms (− 786 T > C rs2070744, 4a4b rs869109213, and 894G > T rs1799983) in the eNOS and metabolic syndrome (MetS) were associated with CRC patient survival.


We genotyped three polymorphisms of eNOS (− 786 T > C, 4a4b, and 894G > T) in 312 CRC cases from the Korean population by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) analysis.


Although the three eNOS polymorphisms were not causative of MetS, the TT genotype of the 894G > T polymorphism was associated with a worse survival rate compared with the GG genotype in the CRC group with MetS than in the CRC group without MetS (5-years survival; adjusted HR = 54.777; 95% CI 5.073–591.487 and RFS; adjusted HR = 14.909; 95% CI 1.571–141.528).


The eNOS polymorphisms were not associated with metabolic syndrome prevalence in CRC patients. However, our findings suggest that the eNOS 894G > T polymorphism with MetS was associated with poor clinical outcomes.

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All data generated or analyzed during this study are either included in this published article or are available from the corresponding author on reasonable request.


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This research was supported by Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the Ministry of Health & Welfare (no. HI18C19990200) and supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (no. 2018R1D1A1B07047604). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

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Conceptualization: EJK, JWK, and NKK; Methodology: HSP, CSR; Formal analysis and investigation: EJK, EJK; Writing—original draft preparation: EJK, JWK; Writing—review and editing: EJK, NKK; Funding acquisition: JWK, and NKK; Resources: HJC, JO, HHJ, So YC, and JWK; Supervision: JWK, NKK. All authors have read and approved the manuscript.

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Correspondence to Jong Woo Kim or Nam Keun Kim.

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Conflict of interest

Eun Ju Ko, Eo Jin Kim, Hye Jung Cho, Jisu Oh, Han Sung Park, Chang Soo Ryu, Jung Oh Kim, Hak Hoon Jun, So Young Chong, Jong Woo Kim and Nam Keun Kim declare that they have no conflict of interest.

Ethical approval

All study protocols were reviewed and approved by The Institutional Review Board of CHA Bundang Medical Center and followed the recommendations of the Declaration of Helsinki. Study subjects were recruited from the South Korean provinces of Seoul and Gyeonggi-do between 1996 and 2009. The Institutional Review Board of CHA Bundang Medical Center approved this genetic study in June 2009 (IRB No.2009-08-077).

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Informed consent was obtained from study participants.

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Ko, E.J., Kim, E.J., Cho, H.J. et al. Prognostic significance of three endothelial nitric oxide synthase (eNOS) polymorphisms and metabolic syndrome (MetS) in patients with colorectal cancer. Genes Genom 44, 659–670 (2022).

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