Gene linked to oestrogen levels and breast cancer risk in younger women
ICR scientists have found the first genetic proof of a link between breast cancer in younger women and the sex hormone oestrogen.
Sex hormones such as oestrogen are known to be important in breast cancer development. Previous studies have found that postmenopausal women with higher levels of particular hormones are at greater risk of breast cancer, however the direct evidence in premenopausal women has so far been inconsistent.
The important study – led by scientists at the ICR’s Breakthrough Breast Cancer Research Centre and the London School of Hygiene and Tropical Medicine – revealed an alteration in a gene that is involved in the breakdown of oestrogen and is also associated with a modest reduction in breast cancer risk in pre-menopausal women.
Dr Olivia Fletcher and colleagues first measured markers of hormone levels in the urine and blood of more than 700 healthy premenopausal women, using a process that was specially designed to account for variation in levels during the menstrual cycle. They then examined the women’s DNA, focusing on 42 genes that are known to be involved in the synthesis or breakdown of sex hormones.
When they compared women’s hormone levels with each of the variants that they tested, they identified one genetic variant that was more common in women who had lower urinary levels of a particular oestrogen breakdown product called oestrone glucuronide. The variant was a single letter change in the DNA at position 7q22.1, not far from the CYP3A gene cluster. It was associated with a 22 per cent reduction in urinary oestrone glucuronide levels.
The team then tested this variant in a further 10,551 breast cancer patients and 17,535 healthy controls, and found the DNA change was more common in healthy women. The variant was associated with a modest – nine per cent – reduction in breast cancer risk in women diagnosed at or before age 50, but not in older women.
The study published in the Journal of the National Cancer Institute