Oestrogen and the enigmatic male predominance of gastric cancer.

Gastric cancer is the second most common cause of cancer death worldwide, and annually it causes over 150,000 deaths in Europe and 700,000 deaths globally. The incidence of gastric cancer shows an enigmatic male dominance with a male-to-female ratio of about 2:1. This sex ratio cannot be entirely attributed to the differences in the prevalence of known risk factors between the sexes. This review focuses on the potential role of oestrogen in explaining the male predominance in gastric cancer. Some data argue in favour of sex hormonal influence. Women with a longer fertility life and those on hormone replacement therapy seem to have a decreased risk of gastric cancer, and men who have been treated with oestrogen for prostate cancer have a decreased risk. Use of tamoxifen in women seems to increase their risk of gastric cancer. Animal studies indicate that oestrogen may offer protection against the development of this cancer as for example ovariectomised mice are at an increased risk, whilst administration of female sex hormones decreases the incidence of gastric cancer. Oestrogen may exert its effect by acting on oestrogen receptors (ERs). Both ERalpha, ERbeta and the latest discovered ERbetacx have been identified in gastric tissue. The biological means behind this is not yet clear but various mechanisms have been suggested. There are indications that oestrogen may lead to an increased expression of trefoil factor proteins, which protect mucous epithelia or inhibit the expression of c-erb-2 oncogene.