Delayed rise in incidence of gastric cancer in females results in unique sex ratio (M/F) pattern: Etiologic hypothesis

Background. The age-standardized and cumulative incidence rates of gastric cancer (GCA) are twice as high in males as in females. Methods. Based on age-group-specific (5-year age groups) annual incidence data of GCA among males and females published by 18 cancer registries worldwide, and on a consecutive series of 938 GCAs from Finland, we explored how the male predominance of GCA has changed over the decades and how this male predominance may possibly vary worldwide between populations with high and low gastric cancer incidence. Results. It appeared that the age-group-specific male-to-female (M/F) ratio of the annual GCA incidence is not constant but increases with age, reaches a peak at age around 60, and decreases thereafter. This special form of the M/F curve is not seen in other gastrointestinal (GI) cancer types (colon, rectum, pancreas). This "low-high-low" form of the M/F curve is related to a 10- to 15-year delay in the appearance and onset of GCA of the intestinal type in females compared with males. The age-group-specific M/F ratio rises as the GCA of the intestinal subtype prevails in males and is rare in females before age 60 and starts to decrease after age 60 as the GCA of the intestinal subtype begins to be common also in females. This special form of the M/F curve is globally consistent and similar in countries or populations of high and low GCA incidence. The data from the Finnish Cancer Registry indicate that the age group-specific M/F curve of the annual GCA incidence has, in addition, remained unchanged over the decades (from the 1950s) in spite of a decrease in the annual GCA incidence of more than 70%. In order to examine the role of gastritis-related diseases as a cause of the sex difference in GCA, 1700 consecutive endoscopied outpatients were studied in Finland. In this series, the age-group-specific prevalences of Helicobacter pylori gastritis, atrophic gastritis, or intestinal metaplasia were proportionally as common in males as in females in all age groups except for the youngest one (20-49 years), in which H. pylori nonatrophic gastritis was slightly more common in males than in females. Conclusion. The male predominance of GCA is a global phenomenon, and is similar in populations with high and low GCA incidence, and this predominance is related to a 10- to 15-year delay in the appearance and onset of GCA of the intestinal subtype in females compared with males. It is suggested that sex hormones (estrogens) protect women against GCA, and that GCA begins to be as prevalent in females as in males only after the menopausal age. Another possibility is that a later acquisition of H. pylori gastritis in females than in males causes the relative delay in the appearance and onset of new GCA cases in females compared with males.