Using father's age to explore the role of germ cell mutation as a cause of human cancer

Abstract

It has been conjectured that single-gene mutations in the human sperm or egg may increase the risk of cancer in subsequent offspring. We propose an epidemiological test of this hypothesis, using an observation from paediatric genetics. Children with autosomal dominant disease are occasionally born into previously unaffected families. This signals the probable mutation of a parent's germ cell. Risk of producing these offspring is found to be related to father's age but not to mother's age. This suggests that sex differences in germ cell production lead to a greater accumulation of germ cell mutations in men than women. If germ cell mutations increase with father's age, and if germ cell mutations are associated with subsequent increase in cancer risk, then some association should exist between age of the father (but not the mother) and risk of cancer. We discuss the few available data, and suggest ways that this hypothesis might easily be tested.