Menstrual and Reproductive Factors, Exogenous Hormone Use, and Gastric Cancer Risk in a Cohort of Women From the European Prospective Investigation Into Cancer and Nutrition

Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Avda Gran Via 199-203, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
American journal of epidemiology (Impact Factor: 5.23). 11/2010; 172(12):1384-93. DOI: 10.1093/aje/kwq321
Source: PubMed


The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.

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Available from: Leila Lujan-Barroso, Sep 30, 2015
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    • "In breast cancer, patients treated with anti-estrogen tamoxifen have been identified to exhibit a significantly increased risk of subsequent gastric cancer (15,16). In addition, ovariectomy also significantly increases the risk of gastric cancer in females (17). Taken together, it has been hypothesized that female sex hormones play a protective role against the development of gastric cancer. "
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    ABSTRACT: Previously, a novel variant of estrogen receptor (ER)-α, ER-α36, was identified and cloned and reported to mainly mediate non-genomic estrogen signaling. More recently, we identified that ER-α36 is important for the invasion and lymph node metastasis of human gastric cancer. In the present study, the c-Src signaling pathway was demonstrated to be involved in the non-genomic estrogen signaling mediated by ER-α36 in SGC7901 gastric cancer cells. SGC7901 cells were subjected to the siRNA-mediated knockdown of ER-α36 (PLKO.1-PURO-SP6-ER-α36-L) or transfected with an ER-α36 upregulated expression plasmid (PLJM1-ER-α36-H) and treated with 17β-estradiol (E2β) and PP2, a c-Src protein inhibitor. The expression of ER-α36 and c-src/p-c-Src and cyclin D1 was examined by western blot analysis, and tumor cell growth was analyzed by cell proliferation and nude mouse xenograft assays. The ER variant, ER-α36, was shown to enhance gastric cancer cell proliferation through activation of the membrane-initiated c-Src signaling pathways, indicating that ER-α36 is important for the regulation of proliferation in gastric cancer. In addition, ER-α36 was shown to directly interact with c-Src by immunoprecipitation. The results of the present study indicate that the use of ER-α36 may be a targeted therapeutic approach in gastric cancer.
    Oncology letters 08/2013; 6(2):329-335. DOI:10.3892/ol.2013.1416 · 1.55 Impact Factor
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    • "Cancers of the upper gastrointestinal tract are associated with significant morbidity and mortality. Cancers of the oesophagus and of the stomach are both more common in men than in women and it has been suggested that this may reflect protection offered by exposure to high levels of oestrogens (Lagergren and Nyrén, 1998; Rutegård et al, 2010a); hence there is interest in the possible role played by hormonal factors, including those related to menarche and menopause and to childbearing, in determining risk for these cancers (Duell et al, 2010; Freedman et al, 2010; Rutegård et al, 2010b; Bodelon et al, 2011). Published evidence suggests that risks for cancers of the oesophagus and stomach are reduced in women taking hormone therapy for the menopause (Green et al, 2011). "
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    ABSTRACT: Hormonal factors may influence risk for upper gastrointestinal cancers in women. We examined risk of oesophageal and gastric cancers in relation to reproductive factors in a large UK cohort, the Million Women Study. Among 1,319,409 women aged on average 56 years at recruitment, 1186 incident cancers of the oesophagus and 1194 of the stomach were registered during 11.9 million person-years' observation. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Risks of both oesophageal and gastric cancer were significantly higher in postmenopausal than in pre- or peri-menopausal women (RRs 1.46, 1.07-2.00 and 1.59, 1.15-2.20, respectively; P≤0.01 for both); and, among postmenopausal women, risk was higher the younger women were at menopause (RR, 95% CI per 5 years younger at menopause 1.18, 1.05-1.34 for oesophageal cancer and 1.18, 1.04-1.34 for stomach cancer, P(trend)=0.01 for both). For factors relating to childbearing, including women's age at first birth, their number of children, and breastfeeding history, the only significant association was a higher risk of oesophageal cancer in nulliparous, compared with parous, women (RR 1.31, 1.11-1.55; P=0.002). When risks for squamous cell and adenocarcinomas of the oesophagus were compared, most did not differ significantly, but statistical power was limited. Both oesophageal and gastric cancer risks appeared to be related to menopausal status and age at menopause, but there was little consistent evidence for associations with factors related to childbearing.
    British Journal of Cancer 11/2011; 106(1):210-6. DOI:10.1038/bjc.2011.525 · 4.84 Impact Factor
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    ABSTRACT: Osteopontin (OPN) is involved in the gastric cancer progression. The study validated whether OPN expressions correlate with Helicobacter pylori-related chronic gastric inflammation and the precancerous change as intestinal metaplasia (IM). This study included 105 H. pylori-infected patients (63 without and 42 with IM) and 29 H. pylori-negative controls. In each subject, the gastric OPN expression intensity was evaluated by immunohistochemistry, and graded from 0 to 4 for the epithelium, lamina propria, and areas with IM, respectively. For the H. pylori-infected subjects, the gastric inflammation was assessed by the Updated Sydney System. Forty-nine patients received follow-up endoscopy to assess OPN change on gastric mucosa after H. pylori eradication. The in vitro cell-H. pylori coculture were performed to test the cell origin of OPN. The H. pylori-infected patients had higher gastric OPN expression than the noninfected controls (p < .001). For the H. pylori-infected patients, an increased OPN expression correlated with more severe chronic gastric inflammation (p < .001) and the presence of IM (OR: 2.6, 95% CI: 1.15-5.94, p = .02). Within the same gastric bits, lamina propria expressed OPN stronger than epithelium (p < .001), suggesting OPN predominantly originates from inflammatory cells. The in vitro assay confirmed H. pylori stimulate OPN expression in the monocytes, but not in the gastric epithelial cells. After H. pylori eradication, the gastric OPN expression could be decreased only in areas without IM (p < .05). Increased gastric OPN expression by H. pylori infection can correlate with a more severe gastric inflammation and the presence of IM.
    Helicobacter 06/2011; 16(3):217-24. DOI:10.1111/j.1523-5378.2011.00832.x · 4.11 Impact Factor
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