The relationship between the epidermal growth factor (EGF) 5'UTR variant A61G and melanoma/nevus susceptibility.

The inheritance of a G allele in position 61 in the 5'UTR of the epidermal growth factor (EGF) gene has been reported to increase melanoma susceptibility, a finding we have investigated in this study. The most potent phenotypic risk factor for melanoma is the atypical mole syndrome (AMS) phenotype. Our hypothesis is that the AMS is genetically determined and that nevus genes are also low penetrance melanoma susceptibility genes. We report that the G allele frequencies were the same in 697 healthy women and 380 melanoma cases (OR 0.97, 95% CI 0.8-1.2 p=0.76). We therefore found no evidence that this polymorphism is a melanoma susceptibility gene. Furthermore, we found no evidence that the polymorphism controls the nevus phenotype (nevus number, number atypical nevi or AMS phenotype). We did find some evidence that the G allele may be associated with decreased tumor Breslow thickness (OR 0.5, 95% CI 0.3-0.9) for the A/A genotype versus A/G and G/G combined in tumors of thickness >3.5 vs < or =3.5 mm and may therefore act as a predictor of survival, although this finding is not in accord with the original report. This is the second study to find no association between EGF +61 and melanoma susceptibility.

Linkage and association analysis of nevus density and the region containing the melanoma gene CDKN2A in UK twins.

Rare mutations in the CDKN2A gene are highly penetrant for melanoma. Density of nevi is under strong genetic control and high density is a potent risk factor for melanoma. We used linkage and association analysis in adolescent twins from the UK to examine the hypothesis that the region containing the CDKN2A gene also contains a quantitative trait locus influencing normal nevus development. Five markers in the CDKN2A region were genotyped in 115 dizygotic twin pairs, and one marker (D9S942) was genotyped in 103 monozygotic twin pairs, all of whom had been phenotyped for nevus density. Linkage analysis showed no evidence of a quantitative trait locus influencing nevus density in this chromosomal region. A model partitioning the variation in phenotype into within- and between-twin pair components showed weak evidence of association between higher nevus density and longer mean length of the two D9S942 alleles (P=0.01). This relation, which was also observed in an earlier Australian twin study, could be because of the linkage disequilibrium between D9S942 and a neighbouring functional locus. Further investigation of this region is warranted in large-scale linkage or association studies.

How complete has skin cancer registration been in the UK? A study from Yorkshire.

The completeness of skin cancer registration in the Yorkshire region was evaluated for the year 1994 by the independent case ascertainment method. Patients diagnosed with skin cancer were identified from regional pathology laboratories, inpatient and outpatient hospital departments and general practices, and were matched against records held by the Northern and Yorkshire Cancer Registry and Information Services (NYCRIS). Out of 5987 skin cancer cases identified from 14 pathology laboratories, 123 general practices, 16 NHS Trusts inpatient databases and 7 dermatology outpatient departments, 83.5% had a matching record on the Cancer Register. The proportion of registered malignant melanoma (MM) and non-melanoma skin cancer (NMSC) cases were 87.5% (95% confidence interval (CI) 84.0-90.4) and 83.1% (95% CI 81.9-84.2) respectively. Skin cancers found in the pathology laboratories, the main notification sources of the registry, were under-ascertained by 15% (10% MM and 15% NMSC). Cases identified from general practices had a significantly lower proportion of matching registry records in comparison with other information sources. No record of histological confirmation could be found for 11% MM and 13% NMSC. Complete capture of pathology laboratory information, histological confirmation of all lesions suspected of skin cancer and routine receipt of hospital patient administration system information supplementary to that from pathology laboratories are measures that would provide the most substantial improvement to ascertainment of skin cancer data.