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Para peneliti menggabungkan varian genetik umum , faktor-faktor lain untuk meningkatkan prediksi risiko kanker payudara

Analisis genom skala besar baru-baru ini telah menemukan puluhan varian genetik umum yang terkait dengan kanker payudara . Setiap varian , namun hanya menyumbang sejumlah kecil risiko keseluruhan seseorang terserang penyakit itu . Sekarang sebuah tim peneliti internasional telah menggabungkan 77 varian genetik yang  biasa menjadi faktor risiko tunggal yang dapat digunakan untuk meningkatkan identifikasi wanita dengan peningkatan risiko kanker payudara . Faktor ini , yang dikenal sebagai skor risiko poligenik , dibangun dari data genetik dari lebih dari 67.000 wanita .,,,read more

Researchers
combine common genetic variants, other factors to improve breast cancer risk
prediction

Date:

April 3, 2015

Source:

Mayo Clinic

Summary:

Recent large-scale
genomic analyses have uncovered dozens of common genetic variants that are
associated with breast cancer. Each variant, however, contributes only a tiny
amount to a person’s overall risk of developing the disease. Now an
international team of researchers has combined 77 of these common genetic
variants into a single risk factor that can be used to improve the
identification of women with an elevated risk of breast cancer. This factor,
known as a polygenic risk score, was built from the genetic data of more than
67,000 women.

...................

recent large-scale
genomic analyses have uncovered dozens of common genetic variants that are
associated with breast cancer. Each variant, however, contributes only a tiny
amount to a person's overall risk of developing the disease.

A Mayo Clinic-led team of international researchers has now combined 77 of
these common genetic variants into a single risk factor that can be used to
improve the identification of women with an elevated risk of breast cancer.
This factor, known as a polygenic risk score, was built from the genetic data
of more than 67,000 women. The results of the research are published April 2,
2015, in the Journal of the National Cancer Institute (JNCI).

A companion study has extended this finding to show that this measure of
genetic variation can be combined with traditional predictors of breast cancer
risk such as breast density and family history to improve personalized
estimates of breast cancer risk. Those findings appeared in JNCI last month.

"This genetic risk factor adds valuable information to what we already
know can affect a woman's chances of developing breast cancer," says study
co-author Celine Vachon, Ph.D., an epidemiologist at Mayo Clinic. "We are
currently developing a test based on these results, and though it isn't ready
for clinical use yet, I think that within the next few years we will be using
this approach for better personalized screening and prevention strategies for
our patients."

Scientists have known for decades that genetics can play a role in breast
cancer. For example, inheriting a mutation in BRCA1 and BRCA2 genes greatly
increase a woman's risk of developing the disease, but these mutations are rare
and account for less than five percent of all breast cancers. More common
genetic variations known as single nucleotide polymorphisms or SNPs also
contribute to cancer susceptibility, but the individual contributions are too
small to predict breast cancer risk.

In this study, researchers tested whether they could combine the effects of
these individual SNPs into a single risk factor for breast cancer. The
investigators essentially added up information on 77 SNPs from 33,673 breast
cancer patients and 33,381 healthy subjects to derive the polygenic risk score.

They showed that the polygenic risk score could successfully place women
into different categories of risk. Compared to women with an average polygenic
risk score, women in the top 1 percent were three times more likely to develop
breast cancer. In addition, women in the lowest one percent of the score were
at a 70 percent lower risk of developing breast cancer. These results indicate
that the polygenic risk score is as powerful as other known risk factors such
as breast density or family history.

"To do an even better job at risk prediction, we need to include this
genetic profile into breast cancer risk models, along with other relevant
information like family history, lifestyle risk factors, previous biopsies, and
breast density," says study co-author Fergus Couch, Ph.D., a molecular
geneticist and pathologist at Mayo Clinic. "But first we need to make sure
that each of the factors are independent, because if the polygenic risk score
is simply repeating what was already accounted for by some of the other known
risk factors then it won't be valuable in a risk model setting."

Drs. Couch and Vachon conducted a second study to evaluate overlap between
the polygenic risk score and the Breast Imaging Reporting and Data System
(BI-RADS), a breast density measure that is routinely assessed in the clinical
setting. Using data from three clinical studies involving 1,643 breast cancer
patients and 2,397 healthy subjects, the researchers found that both factors
independently contribute information to breast cancer risk.

They incorporated the polygenic risk score into the Breast Cancer Surveillance
Consortium (BCSC) risk-prediction model, which uses breast density, family
history of breast cancer, history of breast biopsy, age and ethnicity to
calculate breast cancer risk. The researchers then compared the five-year risk
prediction calculated using the BCSC model with and without the genetic
information. The addition of the polygenic risk score improved the performance
of the model, helping to place 11 percent of women who eventually got cancer
into a higher risk category where they would have been likely to benefit from
interventions such as MRIs, chemoprevention, or even prophylactic mastectomies.

The findings suggest that both breast density and common genetic variation
are important for risk prediction and should be included in clinical models.
However, the researchers say that larger studies are still needed to test the
ability of these models to estimate risk in the general population.

"There have been a lot of common genetic variants associated with
cancers, not just for breast cancer but also for ovarian cancer and prostate
cancer, but so far we haven't seen these being used in clinical practice,"
says Dr. Vachon. "In the future, these factors are going to be helpful in
defining who is at highest and lowest risk of cancer and help both patients and
clinicians make better decisions about their care."







Story Source:

The above story is based on materials provided by Mayo Clinic. Note: Materials may be edited
for content and length.







Journal Reference:

1.    C. M. Vachon, V. S. Pankratz, C. G.
Scott, L. Haeberle, E. Ziv, M. R. Jensen, K. R. Brandt, D. H. Whaley, J. E.
Olson, K. Heusinger, C. C. Hack, S. M. Jud, M. W. Beckmann, R. Schulz-Wendtland,
J. A. Tice, A. D. Norman, J. M. Cunningham, K. S. Purrington, D. F. Easton, T.
A. Sellers, K. Kerlikowske, P. A. Fasching, F. J. Couch. The
Contributions of Breast Density and Common Genetic Variation to Breast Cancer
Risk. JNCI Journal of the National Cancer Institute, 2015; 107
(5): dju397 DOI: 10.1093/jnci/dju397

http://www.sciencedaily.com/releases/2015/04/150403095903.htm

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