Original ResearchAssociation of the oestrogen receptor beta with hormone status and prognosis in a cohort of female patients with colorectal cancer
Introduction
Oestrogens regulate various physiological processes such as reproduction, development, cell growth and differentiation [1]. Abnormalities in oestrogen signalling lead to different types of pathological conditions, including metabolic diseases and cancer [1], [2]. Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide [3]. Gender has been shown to influence CRC localisation and survival. Proximal (right-sided) colon cancer is more common among women, while distal (left-sided) colon cancer and rectal cancer are more common among men [4], [5]. Some studies have reported better overall survival (OS) in women after CRC surgery [6], [7], but other studies indicated no gender differences [8], [9]. Younger women have better survival than younger men, whereas an opposite gender pattern has been shown among older patients [10], [11], [12]. Furthermore, the use of oral contraceptives and hormone replacement therapy (HRT) has been reported to play a protective role in the prevention of CRC [13], [14], [15]. All these data indicate the prognostic relevance of hormone status and oestrogens in CRC.
Oestrogens act via two main receptors—oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ), both of which are members of the nuclear receptor family [1], [16]. ERβ is the predominant oestrogen receptor in the normal colon mucosa, and its loss in CRC has been associated with advanced stages of cancer and poorly differentiated tumours [17], [18], [19]. Previous studies suggested an association between ERβ expression and CRC survival, with consistent results showing that high nuclear ERβ expression leads to a better prognosis [20], [21]. However, these studies did not stratify the population based on gender.
Therefore, we sought to investigate whether ERβ expression was independently associated with OS and disease-free survival (DFS) in a cohort of female patients with CRC. Furthermore, we investigated the association between ERβ expression and tumour characteristics, hormone status and lifestyle indicators.
Section snippets
Study design and study population
Female patients those who were diagnosed and treated for primary CRC, who were physically and mentally able to participate, who could effectively communicate in Swedish and were residents within the study region were eligible. All participants gave written informed consent. This study was approved by the Ethical Committee at Lund University.
This investigation involves 333 tumour samples from female patients who underwent surgery for CRC between 1st January 2008 and 30th June 2012 and were
Distribution of clinical parameters and tumour characteristics between patients with low and high ERβ expression
Measurement of ERβ expression was successful in 314 of 320 samples (98%). Among these, 182 (58%) had low ERβ expression, and 132 (42%) had high expression. The clinicopathological characteristics of the patients based on ERβ expression are shown in Table 1 The mean age ± standard deviation of the study population was 70 ± 11 years (range 37–90). No statistically significant difference was found regarding age and BMI between the low and high ERβ expression groups. Patients with high ERβ
Discussion
Oestrogens are linked to carcinogenesis in endocrine-associated tissues (ovary, uterus, breast and prostate) and are also implicated in different cancer types of non-endocrine-related tissues such as lung and gastrointestinal tissues [23]. ERβ is the predominant oestrogen receptor in the normal colon mucosa, and substantial evidence has demonstrated an inverse relationship between ERβ expression and cancer stage and tumour differentiation [17], [18], [19]. In the present study, we showed that
Conflict of interest statement
None declared.
Disclosure statement
This publication reflects the views of the authors alone, and the European Commission cannot be held responsible for any use, which may be made of the information contained herein. The funding sources had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding information
The study was supported by grants to A.S. from the Malmo University Hospital Cancer Foundation, the Swedish Cancer Foundation (grant number 15 0863), Gunnar Nilsson's Cancer Foundation, and by government funding for clinical research from the National Health Services. This research has been funded with support from the European Commission.
Acknowledgements
The authors would like to thank Kristina Ekström-Holka for her technical assistance. They also would like to thank the study participants and greatly appreciate the help of the hospitals, pathology departments and cooperating institutions for providing all the necessary information.
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