We report a genome-wide association study of melanoma, conducted by GenoMEL, of 2,981 cases, of European ancestry, and 1,982 study-specific controls, plus a further 6,426 French and UK population controls, all genotyped for 317,000 or 610,000 SNPs.,The analysis confirmed previously known melanoma susceptibility loci.,The 7 novel regions with at least one SNP with p<10−5 and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Houston, Texas).,Additional replication came from UK and Dutch case-control series.,Three of the 7 regions replicated at p<10−3: an ATM missense polymorphism (rs1801516, overall p=3.4×10−9); a polymorphism within MX2 (rs45430, p=2.9×10−9) and a SNP adjacent to CASP8 (rs13016963, p=8.6×10−10).,A fourth region near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication.,Unlike the previously known regions, the novel loci showed no association with nevus or pigmentation phenotypes in a large UK case-control series.
Treatment of uveal (intraocular) melanoma is aimed at prolonging life, if possible conserving the eye and useful vision.,About 50% of patients develop fatal metastatic disease despite successful eradication of the primary intraocular tumour.,The effect of ocular treatment on survival is unknown, because the same survival data from case series can be interpreted in different ways.,Treatment is therefore based on intuition and varies greatly between centres.,Randomised trials of treatment vs non-treatment of asymptomatic tumours are desirable but would be controversial, difficult, expensive and possibly inconclusive.,Strategies for coping with uncertainty are needed to avoid unethical care.