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Estrogen and Risk of Gastric Cancer: A Protective Effect in a Nationwide Cohort Study of Patients with Prostate Cancer in Sweden

Departments of ¹ Surgical Sciences and ² Pathology and Cytology, Karolinska University Hospital; and ³ Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Requests for reprints: Mats Lindblad, Department of Surgical Sciences, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Phone: 46-8-517-72-801; Fax: 46-8-33-15-87. E-mail: mats.lindblad{at}karolinska.se

Background: The global pattern of male predominance in gastric cancer incidence remains unexplained. We tested the hypothesis that estrogen prevents gastric cancer in a cohort of men heavily exposed to estrogen.

Methods: We conducted a nationwide cohort study of men with a diagnosis of prostate cancer recorded in the Swedish Cancer Register in 1961-2000. Because estrogen therapy was the treatment of choice for prostate cancer in Sweden between 1950 and 1980, cohort members diagnosed earlier than 1980 were considered exposed to estrogen. Standardized incidence ratios (SIR) estimated relative risk. Complete follow-up was achieved through cross-linkages within the cancer register and the Swedish nationwide registers of emigration and causes of death.

Results: In 515,961 person-years of follow-up, we observed 304 gastric cancers as compared with 349 expected for the cohort members in the predefined "exposed" period 1961-1980, rendering a 13% decreased risk (SIR, 0.87; 95% confidence interval (95% CI), 0.78-0.98). Among patients with a latency of 15 years after a prostate cancer diagnosis in 1961-1980, SIR was 0.57 (95% CI, 0.30-0.97), suggesting a dose-response relation. Similarly, reduced risks were found for cardia cancer and noncardia gastric cancer. No decreased risk was found for the cohort members in 1981-2000, when estrogen treatment was less common (SIR, 0.99; 95% CI, 0.89-1.11).

Conclusions: Our study indicates a reduced risk of gastric cancer in a male cohort exposed to estrogen. These results support the hypothesis that estrogen may prevent gastric cancer, but additional studies are warranted.

Key Words: gastric cancer • estrogen • Gastrointestinal cancers: stomach • Reproductive, hormonal, and related risk factors • Chemoprevention

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