Variation in a genetic element that regulates the expression of the gene encoding caspase-8 (CASP8) is associated with differential susceptibility to several different cancers, according to a study to be published online this week in Nature Genetics.
CASP8 encodes a protein that triggers cell death in response to environmental signals. One of its roles is to regulate the survival of cells of the immune system that are part of the body’s anti-tumor response.
It has been proposed that variation in caspase-8 function or expression might make individuals differentially susceptible to cancer by affecting the population of cells involved in tumor surveillance.
Dongxin Lin and colleagues now report that a newly identified CASP8 variant? a six-nucleotide deletion that reduces the gene’s level of expression? is associated with significantly reduced susceptibility to lung, esophageal, gastric, colorectal, cervical, and breast cancers in Chinese individuals. This work follows up on recent findings that women of European descent with a different CASP8 variant are at modestly reduced risk for breast cancer, and provides strong support for the idea that an individual’s immune status can affect cancer susceptibility.