Some of the disparity in the risk from BRCA mutations is generational. One repeated finding is that, by age 50, mutation carriers born in the early twentieth century seem to have a lower risk of cancer than those born later3. The pattern suggests that outside influences interact with genes, and that something in the environment has changed in an unfavourable way. If researchers can figure out what those influences are, and why they have increased disease prevalence, maybe in the future they will gain new, less invasive tools to delay disease onset — and possibly prevent hereditary cancers altogether.
In 2003, King persuasively showed that the link between BRCA mutations and the risk of cancer varied with time. For Ashkenazi Jewish carriers born after 1940, the likelihood of developing breast cancer by age 50 was nearly triple that of women born before that date. “These people can be in the same family,” says King, who is at the University of Washington, Seattle. “This is not genetic. The whole risk curve is getting shoved younger.” This ‘cohort effect’ has been replicated by numerous researchers over the years, but its meaning is debated.
King attributes the generational shifts in BRCA-associated risks primarily to two trends: earlier starts to menses, and later first pregnancies. Women have been delaying first pregnancies more and more over the course of the past century. Meanwhile, girls now have their first menstruation about two years earlier than they did in the late nineteenth century.
Together, earlier menarche and later first pregnancy have increased the average woman’s exposure to the sex hormone oestrogen, which is thought to promote tumour survival and growth. King believes this lengthened period of oestrogen exposure increases the risk of hereditary and non-hereditary cancers alike.