ReviewOestrogen and the enigmatic male predominance of gastric cancer
Section snippets
Occurrence
Gastric cancer has a high death rate (700,000 per year) making it the second most common cause of cancer death, after lung cancer.1 In the year 2000, almost 200,000 cases were diagnosed in Europe and more than 150,000 deaths occurred2 with a steady and persistent fall in mortality rates.3 The survival rate is better in Japan (52%)1 where endoscopic mass screening has been implemented since the 1960s, whilst the survival chance is about 25% in the Western World.1, 4 The incidence of gastric
Histology
As more than 90% of all gastric cancers are adenocarcinomas, the remainder being mainly non-Hodgkin’s lymphomas, or leiomyosarcomas,6 for the purpose of this review ‘gastric cancer’ refers to gastric adenocarcinoma. According to Laurén’s classification, there are two histological types of gastric adenocarcinoma: intestinal and diffuse.7
The intestinal type is characterised by the glandlike appearance of neoplastic cells, whilst in the diffuse type, as the name implies, the cells lack cohesion
Aetiology
The aetiology of gastric cancer is multifactorial (Fig. 1). H. Pylori infection is a well-established risk factor13, 14 and tobacco smoking is a moderate one.15 A diet rich in fruit and vegetables seems to offer protection16 in contrast to intake of salt, which seems to possibly increase the risk17 as obesity does in the risk of cardia gastric cancer.18, 19 A higher socioeconomic status has also been found to be associated with a reduced risk of gastric cancer, and that risk was stronger for
Hypothesis of oestrogen protection
There is a strong and enigmatic male dominance in the incidence of this cancer with a male-to-female ratio of about 2:1. This male predominance has been observed in different populations of the world, and cannot entirely be explained on the basis of sex differences in the prevalence of known risk factors.22 Therefore, endogenous factors that either provide protection in women alone or imply an increased risk only in men should play a role. A potentially protective effect of oestrogen against
Animal studies
Some animal studies suggest that hormonal factors may play a suppressive role in the development of gastric cancer. The carcinogenic N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) added to drinking water induced gastric cancer in male rats but not in female. In the same experiment, castrated or oestrogen-treated male rats had a lower incidence of gastric cancer compared to untreated male rats.25 Another study reported that the incidence of gastric cancer increased in castrated female rats.26
Human studies
A global pattern in the sex distribution, unique of gastric cancer, has given further support to the hypothesis of oestrogen protection. Sipponen and colleagues showed that women develop the intestinal type of gastric cancer 10–15 years later than men and that the incidence increases after menopause.30 This pattern was consistent in all the 18 cancer registries used in the study and in populations with high and low gastric cancer incidence. The hypothesis that oestrogen might prevent gastric
Biological mechanisms
The discovery of oestrogen receptors in gastric tissue in 1983 ignited an enormous interest in the possible implication of this finding for the treatment of gastric cancer.53 The potential role of involvement of hormonal factors was discussed and some suggested evaluation of hormonal therapy with oestrogen54 or anti-oestrogen.49, 50 It is proposed that the possible protective effect of oestrogen against gastric cancer is exerted through ERs. Two types of ERs are known: ER alpha (ERα)55, 56 and
Summary and future research
The male dominance in the incidence of gastric cancer can at least be partly explained by a protective effect of oestrogen in women. This is probably true for the intestinal type of gastric adenocarcinoma. A summary of the available studies seems to support this hypothesis, but more research is warranted before this can be established. Especially large series in which the two histological subtypes are distinguished need to be done. Another area of research would be to investigate whether
Conflict of interest statement
None declared.
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2021, Archives of Medical ResearchCitation Excerpt :Since the sex difference in gastric cancer risk cannot be totally explained by variations in H. pylori infection, sociodemographic characteristics or environmental factors, sex hormones have been proposed to influence risk of gastric cancer (3). Accumulating evidence supports the role of estrogen in gastric carcinogenesis (4). Normal and tumor gastric cells express estrogen receptors, which could potentially regulate cell growth and clonal expansion.