Women whose egg cells are good at repairing damaged DNA have a longer reproductive life and go through menopause later, a new genetic study suggests.
The downside of later menopause, however, is an increased risk of breast cancer, according to the first ever research to genetically link the age of menopause with breast cancer risk.
The international study, published today in Nature Genetics, also finds the genetic factors that determine when you start menstruating seem to also be involved in when you stop.
“It’s about understanding age at menopause and why some women go through it earlier or later than others,” said one of the study’s authors Professor Roger Milne, an epidemiologist from the University of Melbourne and Cancer Council Victoria.
[This study] suggests there is a much more important role for DNA damage responses in the timing of reproductive ageing than we actually previously realised.
Dr Karla Hutt
“We now know more about the genetic age of menopause and the key biological pathways involved.”
Menopause typically starts when a woman is in her 40s or early 50s, with the average age being 51, in women of European ancestry.
Previous research has suggested that around 21 per cent of the variation in menopause age can be explained by common genetic variants – regions of the genome that vary by just one nucleotide (building block).
To date, however only 18 regions have been identified, explaining just 2.6 per cent of the variation in menopause age, said Professor Milne.
The new study, led by Dr John Perry, Dr Anna Murray and Dr Deborah Thompson from the University of Cambridge, triples the number of genetic regions linked to the age of menopause.
Using data from nearly 70,000 women of European ancestry, the researchers identified 56 genetic variants that help determine whether a woman reaches menopause early or late.
These now explain 6 per cent of the variability in the age at which women get menopause.
“It’s only 6 per cent but it’s a lot more than we knew before,” Professor Milne said.
The findings show there are a “surprisingly narrow range of biological pathways” involved in governing the age of menopause, said the researchers.
They found many of the genetic regions associated with the age of menopause included genes that repair DNA from the damage caused by age.
This suggests oocyte cells in the ovaries that are good at keeping DNA healthy in this way survive longer and delay a woman’s menopause, the researchers said.
“I think what is particularly nice about this study is that it suggests there is a much more important role for DNA damage responses in the timing of reproductive ageing than we actually previously realised,” commented ovarian biologist Dr Karla Hutt of Monash University, who was not involved in the study.
Menopause age linked to breast cancer risk
The new study also found the first genetic link between the age of menopause and breast cancer risk.
Professor Milne said prior to this, it was known that women who had late menopause had a higher risk of breast cancer, but it was not known whether late menopause itself was a cause, or other age-related factors were.
“This kind of genetic analysis establishes that it’s very likely to be causal,” he said.
The researchers believe that earlier menopause reduces breast cancer risk because women have less exposure to the hormone oestrogen over their lifetime.
Many of the genetic variants linked to menopause age also help determine the age of puberty, said Professor Milne.
“The genetic factors that determine when you start menstruating seem to also be involved in when you stop.”