rs6939340

SNPs clustered in one region of chromosome 6p22 have been linked to increased risk for the exceedingly rare childhood cancer known as neuroblastoma. A study involving 720 patients determined that rs6939340(G;G) genotypes had increased likelihood of neuroblastoma development (odds ratio 1.97, CI: 1.58 to 2.45, p=9.3 x 10 -15 ). At-risk homozygotes diagnosed with neuroblastoma had, on average, more malignant clinical presentation, more aggressive disease, and poorer long-term survival. Presumably driven primarily by the at-risk homozygotes, the rs6939340(G) allele was considered to be a risk factor, however, there was insufficient data to conclude whether rs6939340(A;G) heterozygotes were actually at any increased risk compared to rs6939340(A;A) "wild-type" homozygotes. Note that this is an excellent example for putting SNP-associated risks in a relative context of Lifetime Risk. The annual mortality rate for neuroblastoma for everyone combined is 10 per 1 million children in the 0- to 4-year-old age group. Assuming the ~20% of children with the most "at-risk" genotype identified to date, i.e. rs6939340(G;G) homozygotes, have double the risk of the other genotypes, which means their mortality risk has only gone up to ~17 per million, versus the risk for the 80% of individuals with other genotypes going down to ~9 per million. Even if these studies are successfully replicated, odds of 17 out of a million are very very small, so these studies are not useful in predicting disease, even if they may ultimately have benefit in the management of individuals diagnosed with disease. Common variations in BARD1 influence susceptibility to high-risk neuroblastoma.