Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes

Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ov...

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Main Authors: Rafał Watrowski, Eva Schuster, Gerda Hofstetter, Michael B. Fischer, Sven Mahner, Toon Van Gorp, Stefan Polterauer, Robert Zeillinger, Eva Obermayr
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/2/321
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author Rafał Watrowski
Eva Schuster
Gerda Hofstetter
Michael B. Fischer
Sven Mahner
Toon Van Gorp
Stefan Polterauer
Robert Zeillinger
Eva Obermayr
author_facet Rafał Watrowski
Eva Schuster
Gerda Hofstetter
Michael B. Fischer
Sven Mahner
Toon Van Gorp
Stefan Polterauer
Robert Zeillinger
Eva Obermayr
author_sort Rafał Watrowski
collection DOAJ
description Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ovarian cancer (OC), suggesting an association between two IL-8 SNPs and OC risk. In this study, we investigated four common IL-8 SNPs, rs4073 (−251 A>T), rs2227306 (+781 C>T), rs2227543 (+1633 C>T), and rs1126647 (+2767 A>T), using the restriction fragment length polymorphism (PCR-RFLP) technique. Our study included a cohort of 413 women of Central European descent, consisting of 200 OC patients and 213 healthy controls. The most common (73.5%) histological type was high-grade serous OC (HGSOC), whereas 28/200 (14%) patients had endometriosis-related (clear cell or endometrioid) OC subtypes (EROC). In postmenopausal women, three of the four investigated SNPs, rs4073 (−251 A>T), rs2227306 (+781 C>T), and rs2227543 (+1633 C>T), were associated with OC risk. Furthermore, we are the first to report a significant relationship between the T allele or TT genotype of SNP rs1126647 (+2767 A>T) and the EROC subtype (<i>p</i> = 0.02 in the co-dominant model). The TT homozygotes were found more than twice as often in EROC compared to other OC subtypes (39% vs. 19%, <i>p</i> = 0.015). None of the examined SNPs appeared to influence OC risk in premenopausal women, nor were they associated with the aggressive HGSOC subtype or the stage of disease at the initial diagnosis.
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spelling doaj.art-e2f39523e96648adab9722d2ccab676b2024-02-23T15:08:29ZengMDPI AGBiomedicines2227-90592024-01-0112232110.3390/biomedicines12020321Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related SubtypesRafał Watrowski0Eva Schuster1Gerda Hofstetter2Michael B. Fischer3Sven Mahner4Toon Van Gorp5Stefan Polterauer6Robert Zeillinger7Eva Obermayr8Department of Obstetrics and Gynecology, Helios Hospital Muellheim, Teaching Hospital of the University of Freiburg, Heliosweg 1, 79379 Muellheim, GermanyMolecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynaecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, AustriaDepartment of Pathology, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, AustriaDepartment of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, AustriaDepartment of Gynaecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDivision of Gynaecologic Oncology, University Hospital Leuven, 3000 Leuven, BelgiumFaculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyMolecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynaecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, AustriaMolecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center-Gynaecologic Cancer Unit, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, AustriaInterleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ovarian cancer (OC), suggesting an association between two IL-8 SNPs and OC risk. In this study, we investigated four common IL-8 SNPs, rs4073 (−251 A>T), rs2227306 (+781 C>T), rs2227543 (+1633 C>T), and rs1126647 (+2767 A>T), using the restriction fragment length polymorphism (PCR-RFLP) technique. Our study included a cohort of 413 women of Central European descent, consisting of 200 OC patients and 213 healthy controls. The most common (73.5%) histological type was high-grade serous OC (HGSOC), whereas 28/200 (14%) patients had endometriosis-related (clear cell or endometrioid) OC subtypes (EROC). In postmenopausal women, three of the four investigated SNPs, rs4073 (−251 A>T), rs2227306 (+781 C>T), and rs2227543 (+1633 C>T), were associated with OC risk. Furthermore, we are the first to report a significant relationship between the T allele or TT genotype of SNP rs1126647 (+2767 A>T) and the EROC subtype (<i>p</i> = 0.02 in the co-dominant model). The TT homozygotes were found more than twice as often in EROC compared to other OC subtypes (39% vs. 19%, <i>p</i> = 0.015). None of the examined SNPs appeared to influence OC risk in premenopausal women, nor were they associated with the aggressive HGSOC subtype or the stage of disease at the initial diagnosis.https://www.mdpi.com/2227-9059/12/2/321interleukin-8IL-8single-nucleotide polymorphismovarian cancerendometriosis-related cancerpostmenopause
spellingShingle Rafał Watrowski
Eva Schuster
Gerda Hofstetter
Michael B. Fischer
Sven Mahner
Toon Van Gorp
Stefan Polterauer
Robert Zeillinger
Eva Obermayr
Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes
Biomedicines
interleukin-8
IL-8
single-nucleotide polymorphism
ovarian cancer
endometriosis-related cancer
postmenopause
title Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes
title_full Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes
title_fullStr Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes
title_full_unstemmed Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes
title_short Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes
title_sort association of four interleukin 8 polymorphisms 251 a t 781 c t 1633 c t 2767 a t with ovarian cancer risk focus on menopausal status and endometriosis related subtypes
topic interleukin-8
IL-8
single-nucleotide polymorphism
ovarian cancer
endometriosis-related cancer
postmenopause
url https://www.mdpi.com/2227-9059/12/2/321
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