Four genes discovered with significant impact on menopause timing and cancer risk

A new study has discovered the four genes that have the biggest impact. Timing of menopause These previously discovered studies have shed new light on the relationship between the timing of menopause and cancer risk.

Genes exist in pairs, and if a woman has only one copy of the four new genes identified (ETAA1, ZNF518A, PNPLA8, Parv2)Their menopause occurs two to five and a half years earlier than average.

Publication NatureThe large-scale analysis was funded by the UK Medical Research Council and Wellcome. The team first looked at variations in gene sequence data from 106,973 postmenopausal women who participated in the UK Biobank study. The researchers focused on rare types of genetic changes that cause protein loss and investigated their impact on the timing of menopause.

Although all of the genetic variants studied are rare in the population, their effect on menopause is five times greater than any other common genetic variant identified to date. ZNF518AFound in only 1 in 4,000 women, these mutations shorten reproductive lifespan more than most genes identified to date.

Discovering genetic influences will help scientists better understand the biological mechanisms underlying menopausal symptoms and their association with other diseases.

Study co-leader Professor Anna Murray, from the University of Exeter Medical School, said: “For decades the menopause was understudied but it is now a rapidly developing area of ​​science. The timing of menopause has a major impact on how women make their careers and life plans. Understanding genetic changes is of particular interest in terms of potential treatments to extend future reproductive lifespan.”

If unrepaired DNA damage occurs in eggs, they may die. The rate at which eggs are lost determines when a woman will reach menopause. The team's previous work has found that many of the genes that influence the timing of menopause also make women more likely to experience it by affecting the genetic integrity of eggs. The same factors simultaneously affect other cell and tissue types, and in this new study, the team found that many of the genes associated with the timing of menopause are also risk factors for cancer. This includes changes in the BRCA1 and BRCA2 genes that lead to earlier menopause and increased cancer risk.

This is thought to be the process at work in a fifth new gene linked to the timing of menopause (SAMHD1The team found that this genetic change could cause women to enter menopause a year later than average, and for the first time, the researchers have found that it also predisposes to a range of cancers in both men and women.

“Previous research has suggested that women's ovaries age more quickly than other organs in the body, making them a model system for understanding the biology of ageing more broadly. Our latest work builds on this concept and demonstrates that studying ovarian ageing may not only help us better understand the biology behind infertility and other reproductive disorders, but also improve our understanding of the fundamental processes that control DNA damage and cancer risk in the general population.”

Professor John Perry, Co-Leader of the MRC Epidemiology Unit, University of Cambridge

“The researchers then used data from the 100,000 Genomes Project, led by Genomics England and NHS England, to find that mothers with a higher number of genetic mutations that cause early menopause tended to have more new changes in the DNA they passed on to their children. The study authors think this is because the relevant genes are involved in repairing DNA damage, which can lead to impaired function in the ovaries and new genetic changes in eggs.”

Dr Hilary Martin, study co-leader from the Wellcome Sanger Institute, said: “New changes in the DNA of eggs and sperm are the source of all genetic variation in humans, contributing to individual differences in appearance, behaviour and disease risk. Until now, we knew very little about what influences these new DNA changes, apart from parental age. This is the first time we have found that pre-existing common variants in DNA influence the rate of these changes.”

The paper is titled “Ovarian aging, cancer risk, and de novo genetic associations.” mutation The title is “Rate” Nature.