Haptoglobin polymorphism and prostate cancer mortality

Melanie Kaiser,Harald Mangge,Maria Donatella Semeraro,Wilfried Renner,Tanja Langsenlehner,Eva-Maria Thurner,Markus Herrmann

doi:10.1038/s41598-020-69333-z

Melanie Kaiser, Harald Mangge + Show 5 more

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https://doi.org/10.1038/s41598-020-69333-z

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Journal: Scientific Reports	Publication Date: Aug 4, 2020
Citations: 6	License type: open-access

Affiliation: Medical University of Graz

Abstract

Prostate cancer is a common malignancy in men worldwide and it is known that oxidative stress is a risk factor for cancer development. A common functional haptoglobin (Hp) polymorphism, originating from a duplication of a gene segment spanning over two exons, results in three distinct phenotypes with different anti-oxidative capacities: Hp1-1, Hp1-2, and Hp2-2. The aim of the study was to investigate the relationship between this Hp polymorphism and prostate cancer mortality. The study was performed on 690 patients with histologically confirmed prostate cancer, recruited between January 2004 and January 2007. Hp genotypes were determined by a TaqMan fluorogenic 5′-exonuclease assay. Hp1-1 was present in 76 (11%), Hp1-2 in 314 (45.5%), and Hp2-2 in 300 (43.5%) patients. During a median follow-up of 149 months, 251 (35.3%) patients died. Hp genotypes were not significantly associated with higher overall mortality (HR 1.10; 95% CI 0.91–1.33; p = 0.34). This remained similar in a multivariate analysis including age at diagnosis, androgen deprivation therapy, and risk group based on PSA level, GS, and T stage (HR 1.11; 95% CI 0.91–1.34; p = 0.30). We conclude that the common Hp polymorphism does not seem to be associated with overall mortality in prostate cancer patients.

Highlights

Prostate cancer is a common malignancy in men worldwide and it is known that oxidative stress is a risk factor for cancer development
HP genotypes were not associated with tumor stage, Gleason score or risk group
In the majority of patients, follow-up data did not allow to discriminate between prostate cancer specific death and death from other causes. It has been shown in previous studies that Hp polymorphism plays a role in susceptibility to certain cancers and outcome of the d isease[12–14]

Summary

Introduction

Prostate cancer is a common malignancy in men worldwide and it is known that oxidative stress is a risk factor for cancer development. A common functional haptoglobin (Hp) polymorphism, originating from a duplication of a gene segment spanning over two exons, results in three distinct phenotypes with different anti-oxidative capacities: Hp1-1, Hp1-2, and Hp2-2. We conclude that the common Hp polymorphism does not seem to be associated with overall mortality in prostate cancer patients. The accumulation of such radicals in cells results in modification of biomolecules such as proteins, lipids, and DNA These alterations lead to functional impairment of the cell and diseases like cancer or cardiovascular disease. Beyond the task of capturing Hb in the plasma, Hp is a positive acute-phase protein which serves as a bacteriostatic agent, an inhibitor of prostaglandin synthesis and a ngiogenesis[6] It is synthesized in the liver in response to inflammatory cytokines and glucocorticoids[7]. People with Hp1-1 have the highest plasma concentrations, those with Hp2-2 the lowest, and the ones with Hp2-1 have concentrations lying in b etween[11]

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