Association of rs4646903 and rs1048943 CYP1A1 estrogen-metabolizing gene polymorphisms with estrogen receptor-positive breast cancer in Kenyan women

Authors

DOI:

https://doi.org/10.2298/ABS230115005M

Keywords:

Breast cancer, estrogen metabolizing gene, polymerase chain reaction-restriction fragment length polymorphism, genotype, gene polymorphisms

Abstract

Paper description:

  • The rs4646903 and rs1048943 polymorphisms in CYP1A1 estrogen metabolizing gene have shown associations with breast cancer in some populations.
  • A causal-comparative research design was used. Genotyping of the target single-nucleotide polymorphisms was performed using polymerase chain reaction restriction fragment length polymorphism.
  • The variant genotypes CC of rs4646903 and AG and GG of rs1048943 showed significant association with estrogen receptor-positive breast cancer in Kenyan women.
  • Different populations with the same polymorphisms exhibit differences in breast cancer risk. Findings from this study inform on the polymorphisms relevant for risk assessment of breast cancer in Kenyan women.

Abstract: Breast cancer is the most prevalent neoplasm and the second leading cause of death among females in Kenya. Estrogen and its metabolites are known risk factors for breast cancer. Polymorphisms in these genes and breast cancer susceptibility are unique among different populations. This study aimed to determine the probable associations between estrogen-metabolizing gene variations and other risk factors for breast cancer risk in Kenyan women. Buffy coat samples were obtained from patients diagnosed with estrogen receptor-positive breast cancer, benign breast disease, and healthy volunteers. Genotyping of target polymorphisms was conducted using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. The rs4646903 variant genotype CC was associated with breast cancer in the case-control model (P=0.001); the heterozygous genotype TC (P=0.01) and the luminal B molecular subtype (P=0.02) showed increased odds of late-stage breast cancer. The rs1048943 variant genotype GG was associated with breast cancer in the case-benign model (P=0.04), whereas CG was associated with breast cancer in the case-control model (P=0.02). These findings imply that the rs4646903 and rs1048943 variant genotypes are involved in breast cancer risk in Kenyan women. Hence, they may be explored further as potential markers for the disease.

 

Downloads

Download data is not yet available.

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49. https://doi.org/10.3322/caac.21660

Sayed S, Fan S, Moloo Z, Wasike R, Bird P, Saleh M, Shaikh AJ, Figueroa JD, Naidoo R, Makokha FW, Gardner K, Oigara R, Njoroge FW, Magangane P, Mutebi M, Chauhan R, Mwanzi S, Govender D, Yang XR. Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya. Breast Cancer Res. 2021;23(1):1-17. https://doi.org/10.1186/s13058-021-01446-3

McDonald ES, Clark AS, Tchou J, Zhang P, Freedman GM. Clinical diagnosis and management of breast cancer. J Nucl Med. 2016;57:9S-16S. https://doi.org/10.2967/jnumed.115.157834

Pace LE, Shulman LN. Breast Cancer in Sub-Saharan Africa: Challenges and Opportunities to Reduce Mortality. Oncologist. 2016;21(6):739-44. https://doi.org/10.1634/theoncologist.2015-0429

Vanderpuye V, Grover S, Hammad N, Prabhakar P, Simonds H, Olopade F, Stefan DC. An update on the management of breast cancer in Africa. Infect Agent Cancer. 2017;12(1):1-12. https://doi.org/10.1186/s13027-017-0124-y

Gakunga R, Ali Z, Korir A, Kinyanjui AW, Ochieng E, Gikaara N, Maluni F, Subramanian S. Social determinants and individual health-seeking behaviour among women in Kenya: Protocol for a breast cancer cohort feasibility study. BMJ Open. 2019;9(1):e023171. https://doi.org/10.1136/bmjopen-2018-023171

Jameera BA, Jubie S, Nanjan MJ. Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review. Bioorg Chem. 2017;71:257-74. https://doi.org/10.1016/j.bioorg.2017.02.011

Santen RJ, Yue W, Wang JP. Estrogen metabolites and breast cancer. Steroids. 2015;99:61-6. https://doi.org/10.1016/j.steroids.2014.08.003

Sampson JN, Falk RT, Schairer C, Moore SC, Fuhrman BJ, Dallal CM, Bauer DC, Dorgan JF, Shu XO, Zheng W, Brinton LA, Gail MH, Ziegler RG, Xu X, Hoover RN, Gierach GL. Association of estrogen metabolism with breast cancer risk in different cohorts of postmenopausal women. Cancer Res. 2017;77(4):918-25. https://doi.org/10.1158/0008-5472.CAN-16-1717

Blackburn HL, Ellsworth DL, Shriver CD, Ellsworth RE. Role of cytochrome P450 genes in breast cancer etiology and treatment: effects on estrogen biosynthesis, metabolism, and response to endocrine therapy. Cancer Causes Control. 2015;26(3):319-32. https://doi.org/10.1007/s10552-014-0519-7

Francis AM, Ramya R, Ganesan N, Kumarasamy P, Paul SFD, Munirajan AK, Divya M. Breast cancer susceptibility genes in estrogen metabolizing pathway in a southern Indian population. Meta Gene. 2019;19:225-34. https://doi.org/10.1016/j.mgene.2018.12.009

Zhou Y, Ingelman-Sundberg M, Lauschke V. Worldwide Distribution of Cytochrome P450 Alleles: A Meta-analysis of Population-scale Sequencing Projects. Clin Pharmacol Ther. 2017;102(4):688-700. https://doi.org/10.1002/cpt.690

Newman LA. Breast Cancer Disparities: Socioeconomic Factors versus Biology. Ann Surg Oncol. 2017;24(10):2869-75. https://doi.org/10.1245/s10434-017-5977-1

Golmohammadzadeh G, Mohammadpour A, Ahangar N, Shokrzadeh M. Polymorphisms in phase I (Cyp450) genes CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP19A1 (rs749292) and CYP2C8 (rs1058930) and their relation to risk of breast cancer: A case-control study in Mazandaran province in north of Iran. Open Access Maced J Med Sci. 2019;7(15):2488-96. https://doi.org/10.3889/oamjms.2019.667

Anyigba CA, Awandare GA, Paemka L. Breast cancer in sub-Saharan Africa: The current state and uncertain future. Exp Biol Med. 2021;246(12):1377-87. https://doi.org/10.1177/15353702211006047

Boyapati SM, Xiao OS, Gao YT, Cai Q, Jin F, Zheng W. Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women. Cancer. 2005;103(11):2228-35. https://doi.org/10.1002/cncr.21056

Thomas AS, Kidwell KM, Oppong JK, Adjei EK, Osei-Bonsu E, Boahene A, Jiagge E, Gyan K, Merajver SD. Breast cancer in Ghana: Demonstrating the need for population-based cancer registries in low- And middle-income countries. J Glob Oncol. 2017;3(6):765-72. https://doi.org/10.1200/JGO.2016.006098

Adebamowo CA, Famooto A, Ogundiran TO, Aniagwu T, Nkwodimmah C, Akang EE. Immunohistochemical and molecular subtypes of breast cancer in Nigeria. Breast Cancer Res Treat. 2008;110(1):183-8. https://doi.org/10.1007/s10549-007-9694-5

Amadori D, Serra P, Bravaccini S, Farolfi A, Puccetti M, Carretta E, Medri L, Nanni O, Tumedei MM, Kahima J, Masalu N. Differences in biological features of breast cancer between Caucasian (Italian) and African (Tanzanian) populations. Breast Cancer Res Treat. 2014;145(1):177-83. https://doi.org/10.1007/s10549-014-2903-0

Jedy-Agba E, McCormack V, Adebamowo C, Dos-Santos-Silva I. Stage at diagnosis of breast cancer in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Glob Health. 2016;4(12):e923-35. https://doi.org/10.1016/S2214-109X(16)30259-5

Sayed S, Moloo Z, Wasike R, Bird P, Oigara R, Govender D, Kibera J, Carrara H, Saleh M. Is breast cancer from Sub Saharan Africa truly receptor poor? Prevalence of ER/PR/HER2 in breast cancer from Kenya. Breast. 2014;23(5):591-6. https://doi.org/10.1016/j.breast.2014.06.006

Pace LE, Mpunga T, Hategekimana V, Dusengimana J-MV, Habineza H, Bigirimana JB, Mutumbira C, Mpanumusingo E, Ngiruwera JP, Tapela N, Amoroso C, Shulman LN, Keating NL. Delays in Breast Cancer Presentation and Diagnosis at Two Rural Cancer Referral Centers in Rwanda. Oncologist. 2015;20(7):780-8. https://doi.10.1634/theoncologist.2014-0493. https://doi.org/10.1634/theoncologist.2014-0493

Cutler DM, Lleras-Muney A. Understanding differences in health behaviors by education. J Health Econ. 2010;29(1):1-28. https://doi.org/10.1016/j.jhealeco.2009.10.003

Mohammed AA. The clinical behavior of different molecular subtypes of breast cancer. Cancer Treat. Res. Commun. 2021;29:100469. https://doi.org/10.1016/j.ctarc.2021.100469

Balmukhanov TS, Khanseitova AK, Nigmatova VG, Varchenko SP, Talaeva SZ. Associations of Polymorphisms of the CYP 1 A 1 and CYP 1 B 1 Cytochrome P450 Genes with Breast Cancer in Kazakhstan. Adv Breast Cancer Res. 2013;2(3)51-5.

Wang H, Wang WJ. Relationship between CYP1A1 polymorphisms and invasion and metastasis of breast cancer. Asian Pac J Trop Med. 2013;6(10):835-8. https://doi.org/10.1016/S1995-7645(13)60148-0

Mescher M, Haarmann-Stemmann T. Modulation of CYP1A1 metabolism: From adverse health effects to chemoprevention and therapeutic options. Pharmacol Ther. 2018;187:71-87. https://doi.org/10.1016/j.pharmthera.2018.02.012

Ibrahem SQ, Ahmed HQ, Amin KM. Genetic Variations in Cytochrome P450 1A1 and 1B1 Genes in a Cohort of Patients from Iraq Diagnosed with Breast Cancer. Breast Cancer. 2021;15:11782234211050727. https://doi.org/10.1177/11782234211050727

Pescatori S, Berardinelli F, Albanesi J, Ascenzi P, Marino M, Antoccia A, di Masi A, Acconcia F. A tale of ice and fire: The dual role for 17β-estradiol in balancing DNA damage and genome integrity. Cancers (Basel). 2021;13(7):1583. https://doi.org/10.3390/cancers13071583

Tolba W, Rizk El Baz, Othman AI, Roshdy S, Settin A. Polymorphisms of Estrogen Biosynthesis and Metabolizing Genes in Egyptian Women With Breast Cancer. Int J Adv Res (Indore). 2017;5(5):453-64. https://doi.org/10.21474/IJAR01/4131

Chen C, Huang Y, Li Y, Mao Y, Xie Y. Cytochrome P450 1A1 (CYP1A1) T3801C and A2455G polymorphisms in breast cancer risk: A meta-analysis. J Hum Genet. 2007;52(5):423-35. https://doi.org/10.1007/s10038-007-0131-8

Moreno-Galván M, Herrera-González NE, Robles-Pérez V, Velasco-Rodríguez JC, Tapia-Conyer R, Sarti E. Impact of CYP1A1 and COMT genotypes on breast cancer risk in Mexican women: A pilot study. International J Biomark. 2010;25(3):157-63. https://doi.org/10.1177/172460081002500306

Miyoshi Y, Takahashi Y, Egawa C, Noguchi S. Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women. Breast J. 2002;8(4):209-15. https://doi.org/10.1046/j.1524-4741.2002.08404.x

Hussain T, Alrokayan S, Upasna U, Pavithrakumari M, Jayapriya J, Kutala VK, Naushad SM. Meta-analysis of genetic polymorphisms in xenobiotic metabolizing enzymes and their association with breast cancer risk. J Genet. 2018;97(2):523-37. https://doi.org/10.1007/s12041-018-0946-4

Downloads

Published

2023-04-03

How to Cite

1.
Murithi M, Nyanjom S, Mobegi V, Shahin S, Makokha F. Association of rs4646903 and rs1048943 CYP1A1 estrogen-metabolizing gene polymorphisms with estrogen receptor-positive breast cancer in Kenyan women. Arch Biol Sci [Internet]. 2023Apr.3 [cited 2024Nov.21];75(1):57-6. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/8342

Issue

Vol. 75 No. 1 (2023)

Section

Articles

License

Copyright (c) 2023 Ms. , Dr., Dr. , Dr. , Dr.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.