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Angiotensin I-converting enzyme inhibitors/angiotensin II receptor blockers may reduce tumor recurrence in left-sided and early colorectal cancers

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

Angiotensin signaling is suggested to be involved in tumorigenesis, tumor proliferation, and metastases. In colorectal cancer (CRC), it was demonstrated that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may reduce the risk of CRC; however, their impact on tumor recurrence remains unknown. Therefore, in this study, we evaluated the impact of ACEIs/ARBs on tumor recurrence in CRC patients.

Patients and methods

We retrospectively investigated the clinicopathological data of 461 stage I–III CRC patients. We divided the patients into those who took an ACEI and/or ARB (the ACEI/ARB+ group) and those who did not (the ACEI/ARB− group), and we compared the two groups’ recurrence-free survival (RFS) using a Kaplan-Meier curve analysis and log rank test. We also examined the impact of AGTR1 expression on tumor recurrence, using two public CRC datasets.

Results

The Kaplan-Meier curves showed a trend toward improved RFS in the ACEI/ARB+ group versus the ACEI/ARB− group (p = 0.063). Subgroup analyses demonstrated that the RFS was significantly better in the ACEI/ARB+ group versus the ACEI/ARB− group in the patients with left-sided CRC (p = 0.030) and those with stage I CRC (p = 0.009). Consistent with these findings, the AGTR1 expression was higher in the left-sided versus right-sided colon (p = 0.048). High AGTR1 expression levels were associated with poor RFS in the GSE39582 dataset’s stage I–III CRC patients (p < 0.001), and this finding was also validated in the GSE17536 dataset (p = 0.023).

Conclusion

ACEI/ARB treatment may reduce tumor recurrence in left-sided CRC and early-stage CRC.

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Authors and Affiliations

  1. Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan

    Tsuyoshi Ozawa, Yojiro Hashiguchi, Takahiro Yagi, Yoshihisa Fukushima, Ryu Shimada, Tamuro Hayama, Takeshi Tsuchiya, Keijiro Nozawa, Hisae Iinuma & Keiji Matsuda

  2. Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Soichiro Ishihara

Authors
  1. Tsuyoshi Ozawa
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  2. Yojiro Hashiguchi
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  3. Takahiro Yagi
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  4. Yoshihisa Fukushima
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Contributions

Study concept and design, statistical analysis, and manuscript preparation were done by T.O. Data acquisition was done by T.O, Y.O, K.O, T.Y, Y.F, R.S, T.H, T.T, K.N, and H.I. Manuscript editing and review were done by Y.H and S.I.

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Correspondence to Tsuyoshi Ozawa.

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Ozawa, T., Hashiguchi, Y., Yagi, T. et al. Angiotensin I-converting enzyme inhibitors/angiotensin II receptor blockers may reduce tumor recurrence in left-sided and early colorectal cancers. Int J Colorectal Dis 34, 1731–1739 (2019). https://doi.org/10.1007/s00384-019-03379-y

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  • DOI: https://doi.org/10.1007/s00384-019-03379-y

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