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Caspase 8 Story | Breast Cancer October 5, 2007

Posted by ramunas in breast cancer, cancer genetics, familial cancer, research.
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An important example, how we need to interprete association studies with caution between different populations. One recent study published in Nature Genetics and performed on an Asian population (Chinese) reported a six-nucleotide insertion-deletion polymorphism (-652 6N del) in the CASP8 promoter region to be strongly associated with a decreased risk of multiple types of cancer (including lung, esophageal, gastric, colorectal, cervical and breast cancers).

Caspases are important in the life and death of immune cells and therefore influence immune surveillance of malignancies (via) and genetic variants influencing immune status could modify cancer susceptibility. Indeed, the deletion destroys a stimulatory protein 1 binding site and decreases CASP8 transcription and T lymphocytes (could be those my beloved T regs?) with the deletion variant have lower caspase-8 activity and activation-induced cell death upon stimulation with cancer cell antigens.

However, a large study investigating the effect of this deletion in four independent large European BC case-control studies, including data from a total of 7,753 cases and 7,921 controls found, that the CASP8 -652 6N del variant has no significant effect on BC risk in Europeans – the combined per allele odds ratio (OR) was 0.97.

Interestingly, the other variant (D302H (rs1045485)) of caspase 8 gene (CASP8 ) slightly decreases the risk of breast cancer (with odds ratios (OR) of 0.89 for heterozygotes and 0.74 for rare homozygotes, compared with common homozygotes (via)).

“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 told Reuters Health. “It may be also possible to identify combinations of genes which together account for a higher percentage of the familial risk.” (via)

The protein produced by the CASP8 gene participates in programmed cell death, or apoptosis, a defense mechanism that allows cells to commit suicide rather than develop into a tumor. DNA damage can trigger apoptosis, and one hypothesis is that the CASP8 SNP may enhance the body’s ability to clear cancerous cells from the body and thereby lower the risk of breast cancer (via)).

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