Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas

Abstract

Oesophageal and gastric adenocarcinoma share an unexplained male predominance, which would be explained by the hypothesis that oestrogens are protective in this respect. We carried out a nested case -control study of hormone replacement therapy (HRT) among 299 women with oesophageal cancer, 313 with gastric cancer, and 3191 randomly selected control women, frequency matched by age and calendar year in the General Practitioners Research Database in the United Kingdom. Data were adjusted for age, calendar year, tobacco smoking, alcohol consumption, body mass index, hysterectomy, and upper gastrointestinal disorders. Among 1 619 563 person-years of follow-up, more than 50% reduced risk of gastric adenocarcinoma was found among users of HRT compared to nonusers (odds ratio (OR), 0.48, 95% confidence interval (CI) 0.29 -0.79). This inverse association appeared to be stronger for gastric noncardia (OR 0.34, 95% CI 0.14 -0.78) and weaker for gastric cardia tumours (OR 0.68, 95% CI 0.23 -2.01). There was no association between HRT and oesophageal adenocarcinoma (OR 1.17, 95% CI 0.41 -3.32).

Tamoxifen exposure and risk of oesophageal and gastric adenocarcinoma: a population-based cohort study of breast cancer patients in Sweden

“…No decreased risk of oesophageal adenocarcinoma was observed in a cohort of prostate cancer patients treated with oestrogen (Lagergren and Nyren, 1998), or among postmenopausal women treated with oestrogen (Lindblad et al, 2006a). Breastfeeding has been associated with a reduced risk of oesophageal adenocarcinoma (Cheng et al, 2000), a finding that does suggest sex hormonal influence, but childbearing has not been found to be linked with a risk of this cancer (Lagergren and Jansson, 2005).…”

“…Recently, a unique global pattern in the male to female ratio of the incidence of gastric adenocarcinoma was reported, indicating a 10 -15-year delay in this cancer among female subjects compared to male subjects, possibly owing to the oestrogen exposure (Sipponen and Correa, 2002). We have recently reported that men with oestrogen-treated prostate cancer have a reduced risk of developing gastric adenocarcinoma (Lindblad et al, 2004), and in postmenopausal women on HRT, the risk of gastric non-cardia adenocarcinoma seems to be more than 50% lower than in those not receiving such therapy (Lindblad et al, 2006a). Some reproductive factors have also been studied in relation to gastric cancer risk.…”

“…Whereas the limited available literature does not support a role of oestrogen in the aetiology of oesophageal adenocarcinoma (Lagergren and Nyren, 1998;Lagergren and Jansson, 2005;Lindblad et al, 2006a), data are accumulating in favour of oestrogen influence on the aetiology of gastric adenocarcinoma, a decreased risk of which has been reported among women treated with postmenopausal hormone replacement therapy (HRT) (Lindblad et al, 2006a) and among men with prostate cancer treated with oestrogen (Lindblad et al, 2004), suggesting that oestrogen has a protective effect.…”

Cyclin D1/cdk4, estrogen receptors .ALPHA. and .BETA., in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis: immunohistochemical study

“…A large epidemiological study of human gastric cancer has demonstrated that it occurs predominantly in males, and suggested the possibility that estrogen decreases the risk of gastric carcinogenesis (Lindblad et al, 2004. However, information concerning the gender difference for gastric cancer risk has been limited Lindblad et al, 2004Lindblad et al, , 2006. MNNG-induced gastric cancers in rats have been described to occur more fre- quently in males than in females (Furukawa et al, 1982), and this also suggested that estrogen may play a suppressive role in gastric carcinogenesis (Campbell-Thompson et al, 1999;Furukawa et al, 1982).…”

Review: Chemoprevention of esophageal adenocarcinoma

“…However, several populationbased case-control and cohort studies have failed to demonstrate a significant association between hormone replacement therapy or other forms of estrogen exposure and risk of EAC Lindblad et al 2006;Lagergren and Jansson, 2005;Lagergren and Nyren, 1998]. …”