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Biomedical subjects

J A Newton Bishop

Publications and source records attributed to J A Newton Bishop.

18 recordsLinked to original sources
PubMed2004

Exposure to the sun and sunbeds and the risk of cutaneous melanoma in the UK: a case-control study.

Migration, latitude and case-control studies have clearly established a link between melanoma and sun exposure. This case-control study of melanoma was set up to examine the role of sun exposure and sunbeds in the pathogenesis of melanoma in the United Kingdom (UK), a country with low levels of ultraviolet radiation. The study included 413 cases and 416 controls. More than 10 severe sunburns compared with less than 10 sunburns was associated with an Odds Ratio (OR) of 1.98 (95% Confidence Interval (CI) 1.02-3.86) (P=0.04) when adjusted for age, gender and skin type. Sunburns before the age of 15 years were not associated with melanoma once adjustments for age, gender and skin were made. 31% of women and 16% of the men had used sunbeds. Sunbed users were younger than non-users (40 years versus 51 years, P<0.0001). Ever use of sunbeds gave an adjusted OR of 1.19 (95% CI 0.84-1.68) (P=0.33). The risk of melanoma did not increase with increasing hours or years of sunbed exposure. The risk associated with sunbed use was only significant for young individuals with fair skin for whom there was a significant OR of 2.66 (95% CI 1.66-6.09) (P=0.02) after adjustment for the sun exposure variables. Outdoor occupation and residence in hot countries were not associated with an increased risk of melanoma. The only significant associations in this study were with 10 or more sunburns and the use of a sunbed in young subjects with fair skin. Sunbed use is now becoming more prevalent in Caucasian populations and the results of this study suggest that sunbed usage may moderately affect individuals with sun-sensitive skin types. However, the magnitude of melanoma risk in association with natural and artificial sun exposure is small compared with phenotypic risk factors such as skin type and naevus counts. However, it is possible that the mean lag time of 7 years between exposure to sunbed and melanoma in this study may have led to an under-estimation of the long-term melanoma risk.

Adolescent↗
PubMed2004

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.

5' Untranslated Regions↗
PubMed2003

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.

Adolescent↗
PubMed2003

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.

Ambulatory Care Facilities↗
PubMed2002

U.K. guidelines for the management of cutaneous melanoma.

These guidelines for management of cutaneous melanoma present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. To reflect the collaborative process for the U.K., they are subject to dual publication in the British Journal of Dermatology and the British Journal of Plastic Surgery.

Biopsy↗
PubMed2001

Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study.

Risk factors for melanoma include environmental (particularly ultraviolet exposure) and genetic factors. In rare families, susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK4, with more common, less penetrant genes also postulated. A further, potent risk factor for melanoma is the presence of large numbers of melanocytic nevi so that genes controlling nevus phenotype could be such melanoma susceptibility genes. A large Australian study involving twins aged 12 y of predominantly U.K. ancestry showed strong evidence for genetic influence on nevus number and density. We carried out essentially the same study in the U.K. to gain insight into gene-environment interactions for nevi. One hundred and three monozygous (MZ) and 118 dizygous (DZ) twin pairs aged 10-18 y were examined in Yorkshire and Surrey, U.K. Nevus counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p = 0.009) and higher in Australia (110.4) than in the U.K. (79.2, adjusted to age 12 y, p < 0.0001), and nevus densities were higher on sun-exposed sites (92 per m2) than sun-protected sites (58 per m2) (p < 0.0001). Correlations in sex and age adjusted nevus density were higher in MZ pairs (0.94, 95%CI 0.92-0.96) than in DZ pairs (0.61, 95%CI 0.49-0.72), were notably similar to those of the Australian study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability (65% in the U.K., 68% in Australia). We conclude that emergence of nevi in adolescents is under strong genetic control, whereas environmental exposures affect the mean number of nevi.

Adolescent↗
PubMed1999

Mutation testing in melanoma families: INK4A, CDK4 and INK4D.

The INK4A gene which codes for the cyclin-dependent kinase (CDK) inhibitor INK4A or p16 underlies susceptibility to melanoma in some families. Germline mutations in the gene that codes for the target protein of p16, CDK4, underlie susceptibility in very rare families. We report mutation screening of the INK4A and CDK4 genes in 42 UK families. A total of nine families were identified with INK4A mutations and none with CDK4 exon 2 mutations. These mutations were in 8/22 (35%) families with three or more cases of melanoma and 1/20 (5%) families with only two cases. In one of these nine families a novel single base pair substitution was identified, Gly67Arg. In an attempt to identify another melanoma susceptibility gene, a member of the INK4 family, the p19 INK4D gene has been studied. The p19 gene was sequenced in DNA from the 42 UK families and six additional US families. No mutations were identified.

Carrier Proteins↗
PubMed1999

Isolation of human tumor-specific antibodies by selection of an antibody phage library on melanoma cells.

A human single-chain Fv (scFv) library as fusion to phage was constructed from donors with a high titer of autoantibodies. The library was subjected to three rounds of positive selection on human melanoma cells and negative selection on human peripheral blood mononuclear cells. Two scFv clones, B3 and B4, were isolated that bound melanoma cells in cell ELISA and fluorescence-activated cell sorting. The scFvs were characterized further by immunohistochemistry on a large number of normal human tissues. No cross-reactivity with normal tissues was observed. On the other hand, the target antigens were expressed in sections from several different melanoma patients and in some breast cancer and basal cell carcinoma sections. The unusually high tumor specificity of the B3 and B4 antigens makes them attractive targets for the specific therapy of melanoma. The selection strategy used should be generally applicable to the identification of novel cell surface antigens by antibody phage display.

Antibodies, Neoplasm↗
PubMed1998

Solar keratoses: a risk factor for melanoma but negative association with melanocytic naevi.

Solar keratoses have been associated with increased risk of squamous-cell and basal-cell carcinomas, but their association with melanoma is less clear. This study investigated solar keratoses as a risk factor for cutaneous melanoma in Australia, also associations between solar keratoses and other host factors associated with melanoma. A total-body naevus count was made of 258 melanoma cases and 281 controls recruited from New South Wales, Australia, and solar keratoses were counted on the left forearm. Solar elastosis was also assessed by clinical examination on the face and the side of the neck. Solar keratoses were a significant risk factor for melanoma in Australia. The presence of 10 or more solar keratoses on the left forearm (compared with none) was associated with an odds ratio of 4.7 (95% CI, 2.0-10.9). A highly significant association was found between number of solar keratoses and a past history of multiple basal-cell carcinomas in cases and controls respectively. Numbers of common and atypical naevi decreased significantly with age, while solar keratoses were more common in older individuals. Solar keratoses were found more commonly in men than women in cases and in controls (p < 0.0001). A negative association was found between numbers of common naevi and numbers of solar keratoses in cases and controls, and this remained significant after stratifying for age, gender and hair colour (p < 0.0001 and p < 0.0016 respectively). Solar keratoses were more common in males with melanoma on the head and neck as compared with melanoma on any other site. Solar keratoses and naevi were independently predictive of increased melanoma risk. The fact that these 2 phenotypes were found to be negatively associated suggests that susceptibility to melanoma may be expressed via 2 distinct cutaneous phenotypes which may be genetically determined.

Adolescent↗
PubMed1998

The genetics of melanoma: the UK experience.

Most cancers have rare familial forms and cutaneous melanoma is no exception. The studies carried out on the genetics of these rare types are of great importance because the knowledge gained from them is essential in the counselling of patients. Also of great importance is the information it provides regarding the basic aetiology of melanoma.

Female↗
PubMed1997

Molecular pathology of melanoma.

There has long been a clinical need for improved molecular pathology in melanoma, particularly in the histopathology laboratory where the differentiation of melanoma from its benign counterparts is commonly difficult. The need for improved molecular pathology has recently increased as immunotherapeutic options for the treatment of the tumour evolve. It seems likely that in the relatively near future tumour typing before and during immunotherapy will be needed. The identification of the tumour suppressor gene coding for the protein p16 as an important gene in the pathogenesis of melanoma is of great interest but the identification of oncogenes having a significant role in melanoma carcinogenesis has been slow.

Antigens, Neoplasm↗
PubMed1997

What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Age Factors↗
PubMed1996

Health education about sun and skin cancer: language, ideas and perceptions of young children.

Excessive sunlight in early childhood is thought to be a risk factor for skin cancer. We report the use of the 'draw and write' technique for determining changing perceptions, attitudes and knowledge of young children (aged 4-12 years) to the sun and skin cancer. Children were asked to draw pictures and label them in response to a series of carefully worded invitations and questions. The captions were then analysed to assess changing views and perceptions about particular issues in relation to behaviour in the sun. Four hundred and sixty children completed the exercise. An increasing spiral of knowledge with age about effects of the sun and appropriate behaviour was demonstrated. The study revealed a relatively high level of knowledge. Misconceptions and stereotypes were demonstrated. This technique is a simple and effective way of eliciting information from children about health issues. It provides baseline data for producing material for health education for children in relation to sun and skin. It is also a method of assessing the effectiveness in young children of health promotion initiatives.

Art↗
PubMed1994

Family studies in melanoma: identification of the atypical mole syndrome (AMS) phenotype.

Thirteen families have been studied clinically as the basis for a linkage study of susceptibility to cutaneous melanoma. Previous studies have shown that a number of families with predisposition to melanoma have abnormal naevi, now known as the atypical mole syndrome (AMS) phenotype. Many groups performing linkage studies using families selected from geographical areas with higher rates of melanoma have concentrated on the diagnosis of melanoma to identify presumptive gene carriers. In the UK, in the absence of extended families with multiple cases of melanoma, we have attempted to identify gene carriers through the presence of the AMS phenotype. Previously the AMS phenotype has been poorly defined and so we have developed a scoring system to define the AMS in an attempt to allow for variation in expression among gene carriers. In this report, we document the clinical characteristics of all 13 families and the use of our scoring system. The pattern of inheritance within these selected families of the AMS phenotype with or without melanoma is consistent with a dominant gene.

Analysis of Variance↗
PubMedDate not supplied

Teaching children about skin cancer: the draw-and-write technique as an evaluation tool.

Childhood exposure to sunlight is a risk factor for melanoma. To formulate a meaningful program to educate children about the ill effects of the sun, their extant knowledge base must be determined. We have used the "draw-and-write" technique to assess children's perceptions about the sun, suntans, and skin cancer. A total of 693 school children aged 4 to 13 years were asked to draw pictures and label them in response to a series of carefully worded questions. Awareness of the need to apply sunscreen increased from 44% in children aged 4 to 6 years to 95% in children aged 9 to 10 years. Ten percent of children aged 4 to 6 years already perceived a suntan as attractive. While almost all children were aware of the negative immediate effects of sun exposure, namely sunburn, just 30% of American children aged 11 to 13 were aware that sun exposure is a risk for skin cancer. No differences between boys and girls were seen. The "draw-and-write" technique allows assessment of the attitudes and perceptions of children regarding the sun and skin cancer. It also provides valuable information on which to base health education and evaluate its cost-effectiveness.

Adolescent↗