Seventy two commonly occurring gene variants
- Breast cancer is one of the
most commonly diagnosed cancers as well as one of the leading causes of
- It is caused by a complex
interplay between several genetic and environmental factors
- Several new commonly occurring
gene variants contributing to increased breast cancer risk have been
identified in current study.
associated with a higher risk of developing breast
cancer have been found in the current study undertaken by the
a huge project
consisting of 550 scholars from around 300 different institutions across six
The key findings of the study appear in
the journals Nature
and Nature Genetics
. Of the seventy two, 65 are common variants that increase the
risk of breast cancer
and a further seven
predispose to estrogen-receptor negative breast cancer
, i.e. the subtype of
breast cancer that does not respond to the antiestrogen drug tamoxifen.
Importance of Genetics in Breast Cancer Development
Most of the breast
(nearly 90 percent
are associated with acquired mutations
(alterations) in specific genes or combinations of genes during a woman's
lifetime. Also, certain genes such as BRCA1 and BRCA2 genes are inherited genes that
account for less than 10 percent
of all breast cancers. It is thus evident
that genetics plays an important part in breast cancer development along with
interactions with environmental factors such as diet and lifestyle and exposure
to chemicals and toxins.
‘Commonly occurring gene variants are individually associated with only a modest risk of developing breast cancer but presence of many such variants concurrently multiplies the risk manifold.’
the inherited gene variants are
associated with a high risk
of getting breast cancer; however the commonly occurring gene variants are
associated with only a minute risk
but presence of many such variants
simultaneously increases the risk several fold.
Identification Of New Commonly Occurring Gene Variants
Associated With Breast Cancer
huge project undertaken by the OncoArray
comprised of 550 scientists from around 300
different institutions spread over six continents. Overall, genetic data from 275,000 women, was
analyzed, of whom 146,000
had been diagnosed with breast cancer.
The notable findings of the study
included the following:
- Seventy two gene
variants were identified, of which 65 were commonly occurring variants
and seven were associated with the development of estrogen receptor
negative breast cancer. Following the study the total number of commonly
occurring gene variants is now around 180.
epidemiological data and other data from breast tissue, the team was able to predict the
target genes involved in most breast cancer cases.
study found genetic regions
specifically associated with either estrogen-receptor positive or estrogen
receptor negative breast cancer, confirming the fact that these are
biologically distinct entities with different mechanisms of development.
most of these commonly occurring gene variants were present not within the
genes but in regions of the genome
that was involved in regulating the activity of nearby genes.
Professor Doug Easton from the University
of Cambridge, one of the lead investigators on the study, says: "These
findings add significantly to our understanding of the inherited basis of
breast cancer. As well as identifying new genetic variants, we have also
confirmed many that we had previously suspected. There are some clear patterns in the genetic variants that
should help us understand why some women are predisposed
to breast cancer,
and which genes and mechanisms are involved."
Adds Professor Peter Kraft at Harvard TH
Chan School of Public Health, USA, says: "Given the size of these studies,
we expected that we would find a lot of new breast cancer risk variants, but
the studies tell us a lot more about which genes are involved, revealing many previously unsuspected genes
and genetic mechanisms underlying breast carcinogenesis.
should provide guidance for a lot of future research.
of the Study
The findings of the study have a lot of
far reaching implications and applications including
and predicting the risk of breast
cancer development in all women in general as well as BRCA mutation
It was estimated that one percent of women have a risk of breast cancer 3
times more than the population at large.
In this manner, larger differences in risk may be shown
the genetic variants are combined with
other hormonal and lifestyle factors
that influence breast cancer risk.
the mechanisms of development of estrogen receptor (ER) positive and ER
negative tumors will help develop
newer and effective treatments.
of the study may change the
screening practices and imaging techniques used to detect breast
cancer. For example, women at risk (positive family history) may be
recommended to undergo mammography
from an earlier age. Similarly MRI
may be used in high risk women as it is more sensitive than ultrasound imaging.
In the words of Professor Jacques Simard
at Université Laval, Quebec city, Canada "These (high risk) women may benefit from more intensive
screening, starting at a younger age, or using more sensitive screening
, allowing early detection and prevention of the disease. At the
same time, this personalised information will also be useful to adapt screening
modalities for women at substantially lower risk."
In conclusion the findings of this study
could well be a turning point in breast cancer research and guide many future
research activities as well.
- Overview - Breast Cancer - (https://www.bcaction.org/our-take-on-breast-cancer/environment/)
- Breast Cancer Fact Sheet - (http://www.breastcancer.org/about_us/press_room/press_kit/facts_figures)
- BRCA1 and BRCA2: Cancer Risk and Genetic Testing - (https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet)