Cancer Research Lab

A common coding variant in CASP8 decreases the risk for breast cancer, according to a report in the February 11th advance online publication of Nature Genetics.

“More breast cancer genes will be identified over the next year or so, and this may help define pathways that might be good treatment targets,” Dr. Angela Cox from Sheffield University Medical School, UK said. “It may be also possible to identify combinations of genes which together account for a higher percentage of the familial risk.”

Dr. Cox and associates in the Breast Cancer Association Consortium genotyped nine single nucleotide polymorphisms (SNPs) for which there was prior evidence of an association with breast cancer.

The consortium’s analysis of more than 16,000 cases and 17,000 controls showed convincing evidence for a protective effect of CASP8 D302H, which results in an aspartic acid to histidine substitution.

Further experiments are required to establish whether D302H itself or another variant in strong linkage disequilibrium with it actually causes the reduction in invasive breast cancer risk, the investigators maintain.

The L10P variant of TGFB1 was associated with an increased risk of invasive breast cancer, the researchers note, and there was borderline evidence of reduced risk for a promoter SNP in IGFBP3 and increased risk of progesterone receptor-positive breast cancer for ATM S49C.

None of the other SNPs showed evidence of an association with breast cancer, the report indicates.

“The value (of this work) is really in helping researchers understand the pathways involved in breast cancer,” Dr. Cox said. “When we have identified a few more of these low-risk genes, we should have a good picture.”