Breast Cancer Risk Varies Among Gene Carriers, Study

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Main Category: Breast Cancer
Also Included In: Cancer / Oncology;  Genetics
Article Date: 09 Jan 2008 - 3:00 PDT

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A new American and Danish study has found that the risk of developing cancer among carriers of the BRCA1 and BRCA2 breast cancer gene mutation varies greatly.

The study is the work of Dr Colin B. Begg, of the Memorial Sloan-Kettering Cancer Center, in New York, and colleagues and is published in the January 9/16 issue of The Journal of the American Medical Association (JAMA).

BRCA1 and BRCA2 are tumour suppressor genes that control cell division and stop cells proliferating too quickly. Certain mutations of these genes cause them to lose control over this process and predispose the carrier to cancer, namely breast, ovarian and prostate.

According to the researchers, while the cancer risk conferred by BRCA1 and BRCA2 has been studied widely, the extent to which it varies among carriers has not. However, size of risk is an important part of decision making in cancer prevention and treatment.

Begg and colleagues genotyped 2,098 women for mutations in BRCA1 and BRCA2 genes. The women were participants in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) study and had had cancer either in one breast only (unilateral) or in the second breast after having had it in the first breast (contralateral).

All the women had had their initial cancer diagnosed before they reached the age of 55, between January 1985 to December 2000. They were asked if any of their first degree female relatives (mother, sister, daughter) had ever received a diagnosis for breast cancer.

The results showed that:

• 73 (5.2 per cent) of the 1,394 women with unilateral breast cancer carried "faulty" genes: 42 had faulty BRCA1 and 31 had faulty BRCA2 mutations.


• 108 (15.3 per cent) of the women with contralateral breast cancer also carried faulty genes: 67 had BRCA1 had 41 with BRCA2 mutations.


• Risk of breast cancer among first degree relatives was significantly linked to participant's age at diagnosis.


• The risk was higher for relatives of women who had contralateral breast cancer as opposed to unilateral breast cancer (odds ratio 1.4).


• After adjusting for these observed characteristics, there remained a significant variation in risk among carrier families.

Begg and colleagues concluded that:

"There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations."

Genetic testing for BRCA2 and BRCA2 mutations is not currently recommended as part of routine cancer screening, wrote the authors, but in the future, as technology advances and costs come down, it could become part of routine population wide genetic screening and form a cornerstone of tailored risk reduction programmes.

For this reason, wrote the authors, it is important that risk estimation is accurate and the sources of risks correctly identified as they will be important factors in the clinical management of women who carry the BRCA1 and BRCA2 mutations.

Breast cancer is the second biggest cause of cancer deaths among American women. In 1997 it killed 44,190 people, of which 290 were men.

Ovarian cancer accounts for fewer deaths but still represents 4 per cent of all female cancers, and in some cases the two cancers are genetically linked.

Scientists have discovered hundreds of variations among BRCA1 and BRCA2 genes.

"Variation of Breast Cancer Risk Among BRCA1/2 Carriers."
Colin B. Begg; Robert W. Haile; Ake Borg; Kathleen E. Malone; Patrick Concannon; Duncan C. Thomas; Bryan Langholz; Leslie Bernstein; Jorgen H. Olsen; Charles F. Lynch; Hoda Anton-Culver; Marinela Capanu; Xiaolin Liang; Amanda J. Hummer; Cami Sima; Jonine L. Bernstein.
JAMA 2008 299: 194-201.
Vol. 299 No. 2, January 9/16, 2008.

Click here for Abstract.

Sources: Journal abstract, JAMA press release, NCBI Genes and Diseases website.

Written by: Catharine Paddock
Copyright: Medical News Today
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