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

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.

• Authors: Tsuyoshi Ozawa, Yojiro Hashiguchi, Takahiro Yagi, Yoshihisa Fukushima, Ryu Shimada, Tamuro Hayama, Takeshi Tsuchiya, Keijiro Nozawa, Hisae Iinuma, Soichiro Ishihara, Keiji Matsuda
• Journal: International journal of colorectal disease (Int J Colorectal Dis) Vol. 34 Issue 10 Pg. 1731-1739 (Oct 2019) ISSN: 1432-1262 [Electronic] Germany
• PMID: 31478086 (Publication Type: Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors

Topics

• Aged
• Angiotensin Receptor Antagonists (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Cohort Studies
• Colon (pathology)
• Colorectal Neoplasms (drug therapy, pathology)
• Databases as Topic
• Disease-Free Survival
• Female
• Humans
• Male
• Multivariate Analysis
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Proportional Hazards Models
• Up-Regulation