Common genetic variant protects against breast cancer
Scientists have confirmed that a common genetic variant – CASP8 – offers modest protection against breast cancer, according to a study to be published online this week in Nature Genetics. The report provides some of the strongest evidence so far that common variants affect the risk of developing breast cancer, and the size of the collaboration sets an important precedent for future studies.Rare mutations in the genes BRCA1 and BRCA2 significantly raise an individual’s risk of breast cancer, but account for only a fraction of the overall variation in genetic risk. More common variants that have a smaller effect on individual risk have been difficult to find, largely due to the size of the studies needed to identify variants of small effect in a convincing manner.The Breast Cancer Association Consortium, which comprises more than 20 collaborating research groups, examined 9 previously reported breast cancer susceptibility variants in at least 10,000 affected women and 10,000 disease-free women in a study led by Angela Cox. For 8 of the 9 genes, the Consortium reported either no association with breast cancer risk, or marginal evidence for an association. For a variant in the gene CASP8, however, they found a significant association. The particular variant assessed in the study is found in approximately 13% of women of European descent, and is protective, lowering the risk of breast cancer by approximately 10%.
Author contact:
Angela Cox (Sheffield University Medical School, UK)Tel: +44 1142712373; E-mail: a.cox@shef.ac.uk

Large-scale survey of mutations in cancer
One of the largest surveys of mutations in human cancers is reported online this week in Nature Genetics. The study provides a preview of results that may be generated by even larger projects such as The Cancer Genome Atlas, set to begin soon.Previous attempts at cataloguing mutations in different types of cancer have relied on DNA sequencing, which can be too expensive when applied to a large number of tumors. Levi Garraway and colleagues applied a previously developed technique called mass spectrometric genotyping to identify the frequency and distribution of 238 known mutations in 17 oncogenes in 1,000 tumors. The genotyping approach is more sensitive than the sequencing approach, identifying more mutations, and simultaneously detects mutations in multiple oncogenes in a cost-effective manner.The authors report that mutations in three of the oncogenes were not found in any of the tumors, while mutations in the other genes were observed in only 30% of the tumors, indicating that many cancer-causing events remain to be discovered. There were relatively few examples where a specific mutation was found more than once, suggesting that mutations occurring at high frequency will be uncommon.
Author contact:
Levi Garraway (Dana-Farber Cancer Institute, Boston, MA, USA)Tel: +1 617 632 6689; E-mail: levi_garraway@dfci.harvard.edu