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Article

The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan

by
Yun-Chi Wang
1,2,†,
Jie-Long He
3,†,
Chung-Lin Tsai
4,†,
Huey-En Tzeng
5,6,
Wen-Shin Chang
1,2,
Shih-Han Pan
2,
Li-Hsiou Chen
1,2,
Chen-Hsien Su
2,
Jiunn-Cherng Lin
7,
Chih-Chiang Hung
8,
Da-Tian Bau
1,2,9,* and
Chia-Wen Tsai
1,2,*
1
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan
2
Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan
3
Department of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung 413305, Taiwan
4
Division of Cardiac and Vascular Surgery, Cardiovascular Center, Taichung Veterans General Hospital, Taichung 407219, Taiwan
5
Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung 407219, Taiwan
6
Ph.D. Program for Cancer Molecular Biology and Drug Discovery, and Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, Taiwan
7
Division of Cardiology, Department of Internal Medicine, Taichung Veterans General Hospital, Chiayi Branch, Chiayi 60090, Taiwan
8
Division of Breast Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung 407219, Taiwan
9
Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413305, Taiwan
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this study.
Life 2024, 14(1), 9; https://doi.org/10.3390/life14010009
Submission received: 28 November 2023 / Revised: 16 December 2023 / Accepted: 18 December 2023 / Published: 20 December 2023
(This article belongs to the Special Issue Epigenetics and Cancer Therapy)
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Abstract

Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an endogenous inhibitor of matrix metalloproteinase-2 and is highly expressed in breast cancer (BC) cases at diagnosis. However, the genetic investigations for the association of TIMP-2 genotypes with BC risk are rather limited. In this study, contribution of TIMP-2 rs8179090, rs4789936, rs2009196 and rs7342880 genotypes to BC risk was examined among Taiwan’s BC population. TIMP-2 genotypic profiles were revealed among 1232 BC cases and 1232 controls about their contribution to BC using a PCR-based RFLP methodology. The TIMP-2 rs8179090 homozygous variant CC genotype was significantly higher in BC cases than controls (odds ratio (OR) = 2.76, 95% confidence interval (95%CI) = 1.78–4.28, p = 0.0001). Allelic analysis showed that C allele carriers have increased risk for BC (OR = 1.39, 95%CI = 1.20–1.62, p = 0.0001). Genotypic together with allelic analysis showed that TIMP-2 rs4789936, rs2009196 or rs7342880 were not associated with BC risk. Stratification analysis showed that TIMP-2 rs8179090 genotypes were significantly associated with BC risk among younger (≤55) aged women, not among those of an elder (>55) age. Last, rs8179090 genotypes were also associated with triple negative BC. This study sheds light into the etiology of BC in Taiwanese women. Rs8179090 may be incorporated into polygenic risk scores and risk prediction models, which could aid in stratifying individuals for targeted breast cancer screening.
Keywords: breast cancer; genotype; polymorphism; tissue inhibitor of metalloproteinase-2 breast cancer; genotype; polymorphism; tissue inhibitor of metalloproteinase-2

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MDPI and ACS Style

Wang, Y.-C.; He, J.-L.; Tsai, C.-L.; Tzeng, H.-E.; Chang, W.-S.; Pan, S.-H.; Chen, L.-H.; Su, C.-H.; Lin, J.-C.; Hung, C.-C.; et al. The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan. Life 2024, 14, 9. https://doi.org/10.3390/life14010009

AMA Style

Wang Y-C, He J-L, Tsai C-L, Tzeng H-E, Chang W-S, Pan S-H, Chen L-H, Su C-H, Lin J-C, Hung C-C, et al. The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan. Life. 2024; 14(1):9. https://doi.org/10.3390/life14010009

Chicago/Turabian Style

Wang, Yun-Chi, Jie-Long He, Chung-Lin Tsai, Huey-En Tzeng, Wen-Shin Chang, Shih-Han Pan, Li-Hsiou Chen, Chen-Hsien Su, Jiunn-Cherng Lin, Chih-Chiang Hung, and et al. 2024. "The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan" Life 14, no. 1: 9. https://doi.org/10.3390/life14010009

APA Style

Wang, Y.-C., He, J.-L., Tsai, C.-L., Tzeng, H.-E., Chang, W.-S., Pan, S.-H., Chen, L.-H., Su, C.-H., Lin, J.-C., Hung, C.-C., Bau, D.-T., & Tsai, C.-W. (2024). The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan. Life, 14(1), 9. https://doi.org/10.3390/life14010009

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