The Significant Impacts of Interleukin-8 Genotypes on the Risk of Colorectal Cancer in Taiwan

Chia-Wen Tsai; Wen-Shin Chang; Te-Cheng Yueh; Yun-Chi Wang; Yu-Ting Chin; Mei-Due Yang; Yi-Chih Hung; Mei-Chin Mong; Ya-Chen Yang; Jian Gu; Da-Tian Bau

doi:10.3390/cancers15204921

The Significant Impacts of Interleukin-8 Genotypes on the Risk of Colorectal Cancer in Taiwan

Cancers (Basel). 2023 Oct 10;15(20):4921. doi: 10.3390/cancers15204921.

Authors

Chia-Wen Tsai^{1

2

3}, Wen-Shin Chang^{1

2

3}, Te-Cheng Yueh^{3

4

5}, Yun-Chi Wang^{1

3}, Yu-Ting Chin^{1

3}, Mei-Due Yang^{3

6}, Yi-Chih Hung^{1

3}, Mei-Chin Mong⁷, Ya-Chen Yang⁷, Jian Gu², Da-Tian Bau^{1

3

8}

Affiliations

¹ Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan.
² Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
³ Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan.
⁴ Division of Colon and Rectal Surgery, Department of Surgery, Taichung Armed Forces General Hospital, Taichung 41152, Taiwan.
⁵ National Defense Medical Center, Taipei 11490, Taiwan.
⁶ Department of General Surgery, China Medical University Hospital, Taichung 404332, Taiwan.
⁷ Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 41354, Taiwan.
⁸ Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan.

Abstract

Interleukin-8 (IL-8), a pro-inflammatory cytokine, is upregulated in CRC and plays an important role in its development and progression. Genetic variants in the IL-8 gene may impact the risk of CRC by modulating IL-8 levels. Our primary objective was to investigate the role of IL-8 genotypes in the development of CRC. To accomplish this, we employed the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze the genotypes of IL-8 rs4017, rs2227306, rs2227543, and rs1126647 in 362 CRC patients and 362 controls. Additionally, we evaluated the interactions between these genotypes and factors such as age, gender, smoking, alcohol consumption, and body mass index (BMI) status in relation to the risk of CRC. Furthermore, we utilized quantitative reverse transcription-PCR to measure the serum IL-8. The results demonstrated a significant difference in the distribution of rs4017 genotypes between the control and case groups (p for trend = 0.0059). Logistic regression analysis revealed that individuals with variant AA genotype had a 1.92-fold higher CRC risk (95% confidence interval [CI] = 1.28-2.89, p = 0.0023). Moreover, carriers of the IL-8 rs4017 AT + AA genotypes exhibited a significant association with CRC risk (odds ratio [OR] = 1.39, 95% CI = 1.02-1.91, p = 0.0460). Additionally, individuals with IL-8 rs4017 AA genotype displayed significantly elevated serum IL-8 compared to those with TT genotype at a 1.73-fold level (p < 0.0001), indicating a correlation between genotype and phenotype. In conclusion, the genotypes of IL-8 rs4017, along with their associated expression levels, can potentially serve as predictive markers for the risk of CRC.

Keywords: IL-8; Taiwan; colorectal cancer; genotype; phenotype; polymorphism.

Grants and funding

This study received significant support from the Taichung Armed Forces General Hospital (TCAFGH-D-112020) and China Medical University Hospital in collaboration with Asia University (CMU111-ASIA-03). The funders had no involvement in the study design, data collection, statistical analysis, decision to publish, or manuscript preparation.