Breast cancer and microbial cancer incidence in female populations around the world: A surprising hyperbolic association

Abstract

Current literature on cancer epidemiology typically discusses etiology of cancer by cancer type. Risks of different cancer types are, however, correlated at population level and may provide etiological clues. We showed previously an unexpected very high positive correlation between breast cancer (BC) and young-adult Hodgkin disease incidence rates. In a population-based case-control study of BC, older ages at the first Epstein-Barr virus exposure, indicated by older ages at onset of infectious mononucleosis, were associated with elevated BC risk. Here we examine BC risk in association with microbial cancer (MC) risk in female populations across the world. MC cancers are cervical, liver and stomach cancers with established causal associations with human papillomaviruses, hepatitis viruses, and helicobacter pylori, respectively. We examined age-adjusted BC and MC incidence rates in 74 female populations around the world with cancer registries. Our analysis suggests that BC and MC rates are inversely associated in a special mathematical form such that the product of BC rate and MC rate is approximately constant across world female populations. A differential equation model with solutions consistent to the observed inverse association was derived. BC and MC rates were modeled as functions of an exposure level to unspecified common factors that influence the 2 rates. In conjunction with previously reported evidence, we submit a hypothesis that BC etiology may have an appreciable link with microbial exposures (and/or immunological responses to them), the lack of which, especially in early life, may elevate BC risk.