SNPwatch: Researchers Identify Genetic Variations Associated With Aggressive Neuroblastoma

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

The benign and malignant forms of neuroblastoma may have different genetic underpinnings, a new study published online this week in Nature Genetics suggests.

Neuroblastomas develop from primitive nerve cells in an embryo or fetus and are one of the most common solid tumors in childhood.  They generally occur in infants and very young children and are rarely found in children over the age of 10.  In many cases the tumor is easily treated or disappears on its own.  But about 50% of the time the cancer spreads throughout the body.  Unfortunately, only about 35% of children with this aggressive form of the disease survive, despite intense treatment.

Recent work showed that DNA variations on chromosome 6 are associated with neuroblastoma, and, more specifically, with the aggressive form of the disease.  In this latest study, the same research team that found the chromosome 6 SNPs further investigated the possibility that different forms of neuroblastoma have different causes.

The scientists compared DNA from about 760 people with high-risk, aggressive neuroblastoma to more than 4,100 disease-free controls and identified several SNPs within the BARD1 gene on chromosome 2 that are associated with the most serious form of disease.  Additional analysis showed that one SNP alone, rs3768716, could account for the effects they saw.  Each copy of a C at this SNP increased the odds of aggressive neuroblastoma by 1.68 times.

When the researchers went back and analyzed DNA from a collection of low- and intermediate-risk neuroblastoma cases, they found that there was no association with rs3768716.

“Our data suggest that genetic initiating events may predispose not only to cancer, but to a particular subphenotype of the disease, and thus to disease outcome.  This may have implications for both screening and identifying critical pathways for targeted therapeutics,” the authors write.

The protein encoded by the BARD1 gene binds to the BRCA1 protein and is considered to be essential for the latter’s ability to keep cells cancer free.  But although mutations in the BRCA1 gene are a known risk factor for breast cancer, BARD1 mutations have not been implicated in that disease.  The association of variations in the BARD1 gene with neuroblastoma reported in this study is the first evidence that this gene is involved in cancer susceptibility.  The authors say that ongoing studies are now focusing on how the SNPs they identified affect the BARD1 gene and ultimately cancer development.

(23andMe customers can see their data for one of the previously reported SNPs on chromosome 6 in the Neuroblastoma Research Report. The Browse Raw Data feature can be used to see data for rs3768716.  According to the authors of this study, the two SNPS independently affect the odds of having neuroblastoma.)






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