Association of genetically determined levels of ER and BC

[Janette]

A study in this week's Journal of the National Cancer Institute, reveals that scientists have discovered the first direct association between genetically determined levels of estrogen in younger women and the risk of breast cancer. Researchers discovered an alteration in a gene, which affects the breakdown of estrogen and is also related to a modest reduction in breast cancer risk in pre-menopausal women.

Dr Olivia Fletcher from the ICR's Breakthrough Breast Cancer Research Centre, the study's senior author, declared:

"This is the first time anyone has found a DNA change that is directly associated both with hormone levels and breast cancer risk in younger women. Scientists have suspected this link exists, but no one has been able to prove it until now. This represents an important step forward in our understanding of the link between hormones and breast cancer. Ultimately, it may have implications for the way we monitor and treat breast cancer."

?Even though this DNA alteration is only one factor in the complex link between breast cancer and hormones, it nevertheless means that these type of alterations could potentially become genetic markers that could prove beneficial in predicting the risk of breast cancer in young women.

It is widely known that sex hormones like estrogen play an important role in breast cancer development. According to previous studies, post-menopausal women with higher levels of particular hormones are more likely to develop breast cancer, although evidence that is directly linked to pre-menopausal women has so far proven to be inconsistent.

Researchers at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR) and the London School of Hygeien and Tropical Medicine (LSHTM), and their team in the UK and Ireland decided to determine which genetic variants are involved in the synthesis or breakdown of sex hormones.

The team measured markers of hormone levels in over 700 healthy pre-menopausal women's urine and blood in a process which was specifically designed to consider hormone level variations during menstrual cycles, before examining 42 genes in the women's DNA, which is known to have an impact in the synthesis or breakdown of sex hormones.

After a comparison of the participants' hormone levels against each of the tested variants, they found one genetic variant called estrone glucuronide, which appeared more frequently in women with lower urinary levels of a particular breakdown product. The variant was linked to a 22% reduction in estrone glucuronide levels and consisted of one single letter change in the DNA at position 7q22.1, which is close to the CYP3A gene cluster. ??

The researchers subsequently assessed this particular variant in a further 10,551 breast cancer patients and 17,535 healthy controls, discovering that the change in DNA change seemed to be more frequent healthy controls. They established a modest 9% reduction in breast cancer risk in women diagnosed at the age of 50 or younger, however, no reduction was observed in women above the age of 50 years.

The team believe that their discovery may have wider implications, given that CYP3A4 belongs to the family of CYP3A genes, which is responsible for breaking down approximately 50% of all clinically used drugs, including some of those used in breast cancer therapy. According to the team, CYP3A4 may influence the way in which women respond to drugs.

Dr. Fletcher concluded:

"As we move towards a future of personalized medicine, we hope to test people's genes to not only decide which drugs to give them, but also to tailor the most effective doses for the individual. This research has revealed that this set of genes warrants further investigation for the effect they may have on the way the body processes drugs."

Written By Petra Rattue
Copyright: Medical News Today