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Background: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops., Objectives: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk., Methods: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls., Results: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites., Conclusions: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk., Objectives: To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors., Methods: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test., Results: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71-4·54] in the Australian study and 2·56 (95% CI 2·23-2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76-0·83) in the Australian study and 0·73 (95% CI 0·70-0·75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0·30 in the Australian study and < 0·001 in the Leeds study., Conclusions: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions., (© 2019 British Association of Dermatologists.)

Background: Guidelines for follow-up of patients with melanoma are based on limited evidence., Objectives: To guide skin surveillance, we developed a risk prediction model for subsequent primary melanomas, using demographic, phenotypical, histopathological, sun exposure and genomic risk factors., Methods: Using Cox regression frailty models, we analysed data for 2613 primary melanomas from 1266 patients recruited to the population-based Genes, Environment and Melanoma study in New South Wales, Australia, with a median of 14 years' follow-up via the cancer registry. Discrimination and calibration were assessed., Results: The median time to diagnosis of a subsequent primary melanoma decreased with each new primary melanoma. The final model included 12 risk factors. Harrell's C-statistic was 0·73 [95% confidence interval (CI) 0·68-0·77], 0·65 (95% CI 0·62-0·68) and 0·65 (95% CI 0·61-0·69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4·75 times higher (95% CI 3·87-5·82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8·0 ± SD 4.1% after the first primary melanoma, and 46·8 ± 15·0% after the second, but varied substantially by risk score., Conclusions: The risk of developing a subsequent primary melanoma varies considerably between individuals and is particularly high for those with two or more primary melanomas. The risk prediction model and its associated nomograms enable estimation of the absolute risk of subsequent primary melanoma, on the basis of on an individual's risk factors, and can be used to tailor surveillance intensity, communicate risk and provide patient education. What's already known about this topic? Current guidelines for the frequency and length of follow-up to detect new primary melanomas in patients with one or more previous primary melanomas are based on limited evidence. People with one or more primary melanomas have, on average, a higher risk of developing another primary invasive melanoma, compared with the general population, but an accurate way of estimating individual risk is needed. What does this study add? We provide a comprehensive risk prediction model for subsequent primary melanomas, using data from 1266 participants with melanoma (2613 primary melanomas), over a median 14 years' follow-up. The model includes 12 risk factors comprising demographic, phenotypical, histopathological and genomic factors, and sun exposure. It enables estimation of the absolute risk of subsequent primary melanomas, and can be used to tailor surveillance intensity, communicate individual risk and provide patient education., (© 2019 British Association of Dermatologists.)

Little is known about the risk of progression of lentigo maligna to lentigo maligna melanoma. We determine the annual risk of progression of lentigo maligna to lentigo maligna melanoma by analysing a prospective population-based survey of recently diagnosed anterior (visible in a mirror) head and neck lentigo malignas and lentigo maligna melanomas. Six hundred eighty-two consecutive patients aged 18-80 years with non-recurrent lentigo maligna or lentigo maligna melanoma, diagnosed between 1 July 2015 and 20 April 2016, were identified from pathology notifications to the New South Wales Cancer Registry (Australia) and sent survey questionnaires soon after diagnosis (median 4.6 months interquartile range: 3.8-5.7). Details of the time the lesion was present and when changes to it were noticed before diagnostic biopsy were ascertained by surveying the patients, of whom 53.5% agreed to participate. There was little difference between the proportions of lentigo maligna melanoma and lentigo maligna in the consenting and non-consenting patients (P = 0.56). Two hundred twenty-eight lentigo maligna (median age 67 years, range: 38-80) and 33 lentigo maligna melanoma (70 years, 43-80) were surveyed. There was no difference between the time lentigo maligna melanoma was present on the skin (median 18 months, range: 0-690) and the time lentigo maligna was (18 months, 0-665) (P = 0.972). The estimated risk of progression of lentigo maligna to lentigo maligna melanoma was 3.5% per year (95% confidence interval: 2.5-5.0). This equates to an average time for lentigo maligna to progress to lentigo maligna melanoma of 28.3 years (95% confidence interval: 20.0-40.5) in this population. Although our data suggests that the annual progression rate of lentigo maligna is more than 25 times greater than previously suggested, the rate is still low.

Background: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes., Objective: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population-based, case-control studies with comparable ancestry but different ambient sun exposure., Methods: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case-control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders., Results: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self-reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk., Conclusions: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self-reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Guidelines recommend that health professionals identify and manage individuals at high risk of developing melanoma, but there is limited population-based evidence demonstrating real-world practices., Objective: A population-based, observational study was conducted in the state of New South Wales, Australia to determine doctors' knowledge of melanoma patients' risk and to identify factors associated with better identification and clinical management., Methods: Data were analysed for 1889 patients with invasive, localised melanoma in the Melanoma Patterns of Care study. This study collected data on all melanoma diagnoses notified to the state's cancer registry during a 12-month period from 2006 to 2007, as well as questionnaire data from the doctors involved in their care., Results: Three-quarters (74%) of patients had doctors who were aware of their risk factor status with respect to personal and family history of melanoma and the presence of many moles. Doctors working in general practice, skin cancer clinics and dermatology settings had better knowledge of patients' risk factors than plastic surgeons. Doctors were 15% more likely to know the family history of younger melanoma patients (<40years) than of those ≥80 years (95% confidence interval 4-26%). Early detection-related follow-up advice was more likely to be given to younger patients, by doctors aware of their patients' risk status, by doctors practising in plastic surgery, dermatology and skin cancer clinic settings, and by female doctors., Conclusion: Both patient-related and doctor-related factors were associated with doctors' recognition and management of melanoma patients' risk and could be the focus of strategies for improving care., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Cutaneous basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) have poorer outcomes if treated when large., Objective: We sought to estimate the growth rate of BCCs and SCCs and examine the relationship of personal, pathway, and cancer factors with cancer size (diameter)., Methods: We surveyed patients, pathology, and treatment for invasive BCCs and SCCs in 1 Australian region in 2000 through 2001., Results: BCC size increased with increasing time since first noticed. Relative to mean size at 0 to 2 months, the mean size ratio was 1.10 at 2 to 8 months and increased steadily to 1.81 at 5 to 10 years (P < .001). Few BCCs were untreated beyond 10 years. There was no consistent evidence that SCC size increased with increasing time. Larger BCCs were independently associated with older age, male sex, no skin checks by a physician, aggressive tumor type, ulceration and lesion-associated scar tissue, and larger SCCs with male sex, skin checks by a physician every 1 to 3 months, and location on limbs., Limitations: Patient recall of dates and lack of thickness for SCCs are limitations., Conclusion: Earlier diagnosis of BCCs, perhaps through skin checks by a physician, may reduce their size and improve outcome. SCC size did not evidently increase with time., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

This study aimed to assess the attitudes, practices and knowledge of general practitioners (GPs) with regards to vitamin D. A cross-sectional survey of a random sample of GPs stratified by location of practice (rural/remote or metropolitan) and employment status (full-time or part-time) in New South Wales (NSW), Australia was conducted. Of 500 respondents, 58.1% (95% CI 53.8-62.4) reported that up to 39% of their tested patients showed vitamin D deficiency or insufficiency and a further 37.7% (95% CI 33.5-41.9) of respondents said that over 40% of their patients were vitamin D insufficient. Vitamin D supplementation and advice to receive more natural sunlight were the most common ways vitamin D insufficiency was managed (97.1%; 95% CI 95.6-98.6 and 82%, 95% CI 78.6-85.4, respectively). Some gaps in knowledge were identified. Most respondents (64%; 95% CI 59.8-68.2) believed that a person of average sun sensitivity required 10 min of direct sun exposure during summer in peak UV time and a further 21.6% (95% CI 18.0-25.2) believed that people required 30 min of direct sun. A third of respondents (33.1%; 95% CI 29.0-37.2) advised their patients to use sun protection at all times during winter. In general, the attitude items showed that respondents expressed greater concern about vitamin D deficiency than skin cancer. The results reveal some confusion in general practice regarding vitamin D, sun exposure, sun protection and skin cancer risk. Some of the advice that GPs are offering may needlessly increase their patients' risk for vitamin D insufficiency or skin cancer., (Copyright © 2011 UICC.)

Purpose: To develop more evidence-based guidelines for the frequency of patient follow-up after treatment of localized (American Joint Committee on Cancer [AJCC] stage I or II) melanoma., Methods: We used data from Melanoma Institute Australia on an inception cohort of 3,081 consecutive patients first diagnosed with stage I or II melanoma between January 1985 and December 2009. Kaplan-Meier curves and Cox models were used to characterize the time course and predictors for recurrence and new primaries. We modeled the delay in diagnosis of recurrence or new primary as well as the number of monitoring visits required using two monitoring schedules: first, according to 2008 Australian and New Zealand guidelines and, second, with fewer visits, especially for those at lowest risk of recurrence., Results: For every 1,000 patients beginning follow-up, 229 developed recurrence and 61 developed new primary within 10 years. There was only a small difference in modeled delay in diagnosis (extra 44.9 and 9.6 patients per 1,000 for recurrence and new primary, respectively, with delay greater than 2 months) using a schedule that requires far fewer visits (3,000 fewer visits per 1,000 patients) than recommended by current guidelines. AJCC substage was the most important predictor of recurrence, whereas age and date of primary diagnosis were important predictors of developing new primary., Conclusion: By providing less intensive monitoring, more efficient follow-up strategies are possible. Fewer visits with a more focused approach may address the needs of patients and clinicians to detect recurrent or new melanoma.

Polymorphisms in six genes involved in nucleotide excision repair of DNA were examined in a large population-based case-control study of melanoma. Genotyping was conducted for 2485 patients with a single primary melanoma (controls) and 1238 patients with second or higher order primary melanomas (cases). Patients were ascertained from nine geographic regions in Australia, Canada, Italy and the United States. Positive associations were observed for XPD 312 Asn/Asn versus Asp/Asp [odds ratio (OR) = 1.5, 95% confidence interval (CI) 1.2-1.9] and XPD 751 Gln/Gln versus Lys/Lys (OR = 1.4, 95% CI 1.1-1.7) genotypes and melanoma. The combined XPD Asn (A) 312 + Gln (C) 751 haplotype was significantly more frequent in cases (32%) compared with controls (29%) (P = 0.003) and risk of melanoma increased significantly with one and two copies of the haplotype (ORs 1.2, 95% CI 1.0-1.4, and 1.6, 95% CI 1.2-2.0, trend P = 0.002). No significant associations were observed for HR23B codon 249, XPG codon 1104, XPC codon 939, XPF codon 415, XPF nt 2063, ERCC6 codon 1213 or ERCC6 codon 1230. ORs for XPD and XPC genotypes were stronger for melanoma diagnosed at an early age, but tests for interaction were not statistically significant. The results provide further evidence for a role of XPD in the etiology of melanoma.

Background: Although sun exposure is an established cause of cutaneous malignant melanoma, possible interactions with host factors remain incompletely understood. Here we report the first results from a large prospective cohort study of pigmentation factors and sun exposure in relation to melanoma risk., Methods: The Women's Lifestyle and Health Cohort Study included 106 379 women from Norway and Sweden who were aged 30-50 years in 1991 or 1992 when they completed an extensive questionnaire on personal characteristics and exposures. Linkages to national registries ensured complete follow-up through December 31, 1999. Poisson regression models were used to estimate relative risks (RRs). All statistical tests were two-sided., Results: During an average follow-up of 8.1 years, 187 cases of melanoma were diagnosed. Risk of melanoma was statistically significantly associated with increasing body surface area (RR for > or =1.79 m2 versus < or =1.61 m2 = 1.60, 95% confidence interval [CI] = 1.03 to 2.48; P(trend) =.02), number of large asymmetric nevi on the legs (RR for > or =7 nevi versus 0 nevi = 5.29, 95% CI = 2.33 to 12.01; P(trend)<.001), hair color (RR for red versus dark brown or black = 4.05, 95% CI = 2.11 to 7.76; P(trend)<.001), sunburns per year at ages 10-19, 20-29, and 30-39 years (P(trend)<.001, P(trend) =.03, and P(trend) =.05, respectively), and use of a device that emits artificial light (solarium) one or more times per month (P =.04)., Conclusions: Our results confirm previous findings that hair color, number of nevi on the legs, and history of sunburn are risk factors for melanoma and suggest that use of a solarium is also associated with melanoma risk. Adolescence and early adulthood appear to be among the most sensitive age periods for the effects of sunburn and solarium use on melanoma risk. However, it may be too early to see the full effect of adult exposures in this cohort.

Data regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case-control studies of melanoma in women completed as of July 1994 for which electronic data were available on oral contraceptive use along with other melanoma risk factors such as hair colour, sun sensitivity, family history of melanoma and sun exposure. Using the original data from each investigation (a total of 2391 cases and 3199 controls), we combined the study-specific odds ratios and standard errors to obtain a pooled estimate that incorporates inter-study heterogeneity. Overall, we observed no excess risk associated with oral contraceptive use for 1 year or longer compared to never use or use for less than 1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74-1.01), and there was no evidence of heterogeneity between studies. We found no relation between melanoma incidence and duration of oral contraceptive use, age began, year of use, years since first use or last use, or specifically current oral contraceptive use. In aggregate, our findings do not suggest a major role of oral contraceptive use on women's risk of melanoma.

There is persuasive evidence that each of the three main types of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, is caused by sun exposure. The incidence rate of each is higher in fairer skinned, sun-sensitive rather than darker skinned, less sun-sensitive people; risk increases with increasing ambient solar radiation; the highest densities are on the most sun exposed parts of the body and the lowest on the least exposed; and they are associated in individuals with total (mainly SCC), occupational (mainly SCC) and non-occupational or recreational sun exposure (mainly melanoma and BCC) and a history of sunburn and presence of benign sun damage in the skin. That UV radiation specifically causes these skin cancers depends on indirect inferences from the action spectrum of solar radiation for skin cancer from studies in animals and the action spectrum for dipyrimidine dimers and evidence that presumed causative mutations for skin cancer arise most commonly at dipyrimidine sites. Sun protection is essential if skin cancer incidence is to be reduced. The epidemiological data suggest that in implementing sun protection an increase in intermittency of exposure should be avoided, that sun protection will have the greatest impact if achieved as early as possible in life and that it will probably have an impact later in life, especially in those who had high childhood exposure to solar radiation.

The incidence of cutaneous malignant melanoma (CMM) has been rising in fair-skinned populations throughout the world for decades. The upward trend may, however, finally be slowing in some of these populations. Recent (1983-1996) CMM incidence trends for a high incidence area (New South Wales, Australia) have been examined according to gender, age group, body site and tumour thickness. Despite continuing upward trends in older age groups, particularly among men (e.g., 7.20% increase per year in men aged 75+), incidence for younger ages is stabilizing (in men) or declining (in women): average annual percentage changes of -3.03 and -0.88 were observed for women aged 15-34 and 35-54, respectively. Patterns suggest a birth-cohort effect, with those born since 1945 or 1950 having lower (females) or similar (males) rates to those born earlier. For each gender, all-ages incidence rose by a similar amount for each of the main body sites except the leg in women, where incidence fell by 0.49% per year. In men, the incidence of both thin (75 mm) melanomas increased (significantly, by 2.63% per year and non-significantly, by 0.93% per year, respectively) between 1989 and 1996. In women, incidence remained stable for both thickness subgroups. These data are consistent with a stabilization or reduction in either total sun exposure or intermittency of exposure among New South Wales cohorts born since about 1950. Because incidence rates are still much higher than they were a few decades ago, however, efforts to reduce sun exposure, particularly in children and youth, must continue., (Copyright 2001 Wiley-Liss, Inc.)

We examined the reproducibility of the measurement of sun exposure in a cohort study of nonmelanocytic skin cancer in Geraldton, Western Australia. Two analyses were undertaken: a comparison of cutaneous sun damage with sun exposure reported at interview, and an analysis of test-retest reproducibility of reported exposure. Skin cancers and cutaneous indicators of sun damage (cutaneous microtopography and solar elastosis of the neck) were recorded at a survey in 1987. A case-control study was conducted in 1988 in which subjects were interviewed about their lifetime sun exposure. All subjects had European ancestry. A subset of these subjects was reinterviewed using the same interview schedule in 1993. The comparison of reported exposure with skin damage was restricted to 201 cases of basal cell carcinoma and 700 controls, all of whom were born in Australia and had no southern European ancestors. The analysis of test-retest reproducibility included 62 cases with basal cell carcinoma and 162 controls. After adjustment for the skin's sensitivity to sunlight, cutaneous microtopography explained 7% and solar elastosis of the back of the neck explained 13% of the variance in the reported time spent outdoors. The intraclass correlation between time spent outdoors reported in the two interviews was 0.77 [95% confidence interval (CI), 0.71-0.83], whereas for exposure to a specific anatomical site, it was 0.65 (95% CI, 0.55-0.73). The reported site-specific exposure was lower on the second occasion in controls but higher in cases. The hours of exposure on vacations and the proportion of exposure that occurred on nonworking days had poor reproducibility. Furthermore, cases reported a more intermittent pattern of weekly exposure on the first occasion than on the second, whereas the controls showed little difference in their pattern on the two occasions. The weighted kappa statistic for lifetime painful sunburns was 0.53 (95% CI, 0.41-0.66), and for lifetime number of blistering sunburns, it was 0.54 (95% CI, 0.44-0.65). Thus, the reported sun exposure showed only moderate agreement with biological markers of sun damage. Total sun exposure and, to a lesser extent, site-specific exposure showed good agreement on the two occasions. However, indicators of intermittent sun exposure had poor agreement, and sunburn had only fair agreement.

We conducted a case-control study of sun exposure and squamous cell carcinoma (SCC) of the skin within a population-based, longitudinal study of skin cancer. Cases had histopathologically confirmed SCC. Subjects were interviewed about their lifetime sun exposure, including exposure to the site of the SCC (sites for controls were assigned randomly). Analysis was restricted to 132 cases and 1,031 controls born in Australia and with no ancestors from southern Europe. The total site-specific exposure was strongly related to risk of SCC; the odds ratio increased to a maximum of 3.3 at 65,000 hr of exposure before falling slightly. Site-specific exposure during childhood and adolescence was more strongly associated with SCC than exposure during adulthood. An intermittent pattern of weekly sun exposure was not associated with SCC and the odds ratios for hours of exposure on vacation were close to unity. The number of blistering sunburns to the site was positively associated with SCC. Use of sunscreens and hats showed inconsistent effects. Sun exposure, especially during childhood and adolescence, increases the risk of SCC. The pattern of exposure appears to be unimportant, despite the association with sunburn, which may simply be an indicator of the skin's sensitivity to sunlight.

We conducted a case-control study of squamous cell carcinoma of the skin (SCC) in a cohort of people followed from 1987 to 1994. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age in 1987. On 2 occasions, in 1987 and 1992, dermatologists examined participants for skin cancers. Subjects were also asked on several occasions about skin cancers that they had had treated. Migrants to Australia had reduced risks of SCC. Furthermore, people who migrated to Australia early in life or, equivalently, lived in Australia for a long time had a higher risk than immigrants who arrived later in life or more recently. People who had southern European ancestry had a much lower risk of SCC than other subjects, most of whom were of British or northern European origin. Among Australian-born subjects of British or northern European ancestry, the skin's sensitivity to sunlight was strongly associated with SCC. The pigmentary traits of hair colour, eye colour and skin colour showed weaker associations. The degree of freckling on the arm was strongly predictive of risk. The risk of SCC increased strongly with increasing evidence of cutaneous solar damage and was most strongly associated with the number of solar keratoses. Our results show that sensitivity to sunlight and high levels of exposure to sunlight are important determinants of the risk of SCC.

Background: A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248: AAC CGG --> AAT TGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure., Methods: This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95% confidence intervals (95% CIs)., Results: Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3-7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site., Conclusions: Our results indicate that tandem CC --> TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV-radiation exposure.

To measure the rate at which non-melanocytic skin cancers develop, we conducted a population-based, longitudinal study in Geraldton, Western Australia. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age and registered on the electoral roll in 1987. In 1987 and again in 1992, dermatologists examined participants for skin cancers. They examined all skin areas, apart from those covered by underwear or hair. Subjects were asked about skin cancers that they had had treated between the 2 surveys. When all skin cancers were counted, the incidence rates of basal cell carcinoma were 3,379 per 100,000 person-years in women and 7,067 per 100,000 in men; those of squamous cell carcinoma were 501 per 100,000 in women and 775 per 100,000 in men. Sixteen percent of men and 14% of women developed at least one basal cell carcinoma; 2.8% of men and 2.2% of women had at least one squamous cell carcinoma. Most incident skin cancers were diagnosed at the second examination. More than half of the subjects who had a skin cancer at the first examination developed another. Squamous cell carcinomas occurred almost exclusively on parts of the body that are usually exposed. Basal cell carcinomas were common on the head, neck and trunk but not on the forearms and backs of hands. A quarter of people with a skin cancer on an exposed site also had one on the trunk. Our results show that skin cancer is extremely common in this population and frequently undiagnosed. Multiple skin cancers occur commonly, and skin cancers on exposed sites often are associated with skin cancers on less exposed sites.

By 1927 for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and by 1955 for melanoma, the broad grounds for relating sun exposure to skin cancer had been established: that these are more frequent in residents of areas of high ambient solar irradiance, are more frequent in sun-sensitive people, occur mainly on sun-exposed body sites, are more frequent in people with high sun exposure, and are more frequent in people with benign sun-related skin conditions. The past 40 years have added both quantity and quality to the epidemiological evidence and, most recently, provided direct evidence that sun exposure is the cause of mutations in critical tumour suppressor genes in BCC, SCC and melanoma. Complete or more convincing answers are still needed to many questions of detail. They include whether the pattern of sun exposure is really important in, and acts independently of amount of sun exposure in, affecting the risk of melanoma and BCC; what the shape of the relationship between the amount of sun exposure and risk of BCC and melanoma is when the pattern of exposure is held constant; whether there really is a plateau in risk of BCC and melanoma beyond some level of the amount of exposure; whether this exposure-response relationship depends on cutaneous sensitivity to the sun and in what way; whether sunburn makes a specific contribution to the risk of skin cancer independent of the amount of sun exposure; whether sun exposure close to the time of diagnosis of skin cancer contributes anything to the development of the cancer; what the solar radiation action spectrum is for each kind of skin cancer; and whether sunscreens are effective in protecting against skin cancer.

Epidemiologic evidence on the relation between sunlight and cancer is reviewed. Strong evidence implicates sunlight as a cause of skin cancer, although, for melanoma and basal cell carcinoma, the relationship is complex. Both types of cancer are associated more strongly with nonoccupational exposure than with occupational exposure, and the pattern and amount of exposure each appear to be important. Squamous cell carcinoma appears to be related more strongly to total (i.e., both occupational and nonoccupational) exposure to the sun. The evidence that sunlight causes melanoma of the eye is weak. It shows no latitude gradient and the results of case-control studies are conflicting. There is inadequate evidence to suggest that sunlight does or does not cause any other type of cancer.

Objective: To describe recent trends in mortality from melanoma in Australia., Design: An analysis of trends in age standardised and age and sex specific mortalities by year of death and median year of birth (cohort)., Setting: Australia., Subjects: All deaths from melanoma registered in Australia between 1931 and 1994., Results: Melanoma mortality rose steadily from 1931 to 1985. From 1959 the annual rate of increase was 6.3% in men and 2.9% in women, resulting in mortalities of 4.82 and 2.51 per 100,000 person years in 1985 and 1989, respectively. Mortalities for both sexes seem to have plateaued from June 1985 onwards. In 1990-4 the rate rose by 3.7% in men to 5.00 per 100,000 and in women it fell by 5.2% to 2.38 per 100,000. The non-significant increase after 1985 in mortality in men was restricted to those aged over 70 years of age, whereas the fall in rates in women was mostly in those aged under 55 years. This pattern was generally reflected in the state trends, though with some variation: rates for women in Queensland had peaked in the late 1970s; while rates for men in New South Wales continued to rise in 1990-4, placing them above those for Queensland. Examination of mortalities specific for age, period, and cohort for Australia as a whole showed several salient features. Rates in men rose steeply in cohorts born before about 1930; were stable in cohorts born between 1930 and 1950; and fell in more recent cohorts. Rates in women showed similar changes but about five years earlier., Conclusion: Melanoma mortality in Australia peaked in about 1985 and has now plateaued. On the basis of trends in cohorts it can be expected to fall in coming years.

In a combined analysis of 2952 melanoma patients and 3618 controls from 8 case-control studies in white populations the risk of cutaneous melanoma was 2.24-fold higher (95% CI, 1.76-2.86) in subjects who reported at least one affected first-degree relative than in subjects who did not. There was no evidence for heterogeneity in the relative risk between the studies, which were from a wide range of latitudes and hence degrees of sun exposure. The effect of family history on melanoma risk was independent of age, naevus count, hair and eye colour, and freckling. There was no evidence for a relationship between family history and primary site of melanoma but there was some suggestion that the familial patients were more likely to have superficial spreading melanoma or lentigo maligna melanoma than acral lentiginous melanoma or nodular melanoma.

Using individual subject data from 10 case-control studies, comprising over 3000 cases and almost 4000 controls, we have estimated the relative risk of melanoma associated with aspects of complexion, namely, hair, eye and skin colour and freckling in adulthood, and have examined the relationships between these factors and naevus count in terms of melanoma risk. Compared with individuals with black or dark brown hair, the relative risks for developing melanoma in those with light brown, blonde and red hair were 1.49 (95% CI 1.31, 1.70), 1.84 (95% CI 1.54, 2.21) and 2.38 (95% CI 1.90, 2.97), respectively. Individuals with blue eyes had a risk 1.55 (95% CI 1.35, 1.78) times that for those with brown eyes, or 1.15 (95% CI 0.94, 1.40) after adjusting for hair colour and freckling in adulthood. The relative risks associated with hair and eye colour were independent of those for naevus count and skin colour. Light skin colour and high freckle density were also highly significant risk factors, independent of each other and of naevus count and hair and eye colour. The risks associated with these factors, while individually modest, are largely independent, and thus pigmentation characteristics and freckling tendency should be useful in identifying high risk groups to be targeted for prevention.

It is estimated that 92,000 new cases of melanoma and 2,750,000 cases of nonmelanocytic skin cancer occur worldwide each year. Incidence of these cancers varies more than 100-fold from low rates in Asian populations to very high rates in the white population of Australia. Incidence of melanoma has been increasing in white populations by some 3% to 7% per year over the past 30 years; recent very sharp increases in some populations are probably due to early and increasing detection of cancers that were already there. Incidence of nonmelanocytic skin cancers probably is also increasing. Sun exposure is the main cause of skin cancer, accounting for at least 65% of melanomas worldwide and a much higher proportion in white populations. Pattern as well as amount of sun exposure is important in determining the risk of melanoma and probably also of basal cell carcinoma, with an intermittent pattern being associated with the greatest risk. There is increasing evidence that nonsolar sources of ultraviolet radiation, in particular sunlamps and sunbeds, increase the risk of melanoma, and PUVA therapy and exposure to ionizing radiation are established causes of nonmelanocytic skin cancer.

During the mid to late 1980s in white populations in Australia, New Zealand, and Scotland, melanoma incidence increased sharply above preceding long-term trends. Most of this increase was in thin melanomas (< 1.50 mm thick), and men were more affected than women. Thick melanomas also generally increased in incidence, particularly in men 65 years or older. Although advancement of the time of diagnosis was a likely factor in the increase in melanoma incidence, the maintenance of new higher incidence levels and the increase in the incidence of thick lesions indicated that earlier diagnosis did not explain most of the increase. Real increases in incidence due to continuation of long-term trends and the increasing diagnosis of a preexisting, nonmetastasizing form of thin melanoma probably explain most of the recent increases in melanoma incidence.

Our report deals with the relationship of pattern and timing of sun exposure to basal cell carcinoma (BCC) in a population-based case-control study conducted in Western Australia in 1988. The main measure of intermittent exposure was based on the amount of exposure on non-working days relative to that over the whole week. Outdoor recreational activities, holidays and sunburn were also considered to be markers of intermittent exposure. We observed a statistically significant increase in risk of BCC with increasing proportion of weekly sun exposure obtained at the weekend, especially in late teenage (OR = 3.9, 95% CI 1.9-7.8 for maximum intermittency of exposure), exposure of the site of skin cancer during holidays (OR = 1.9, 95% CI 1.1-3.1 for the highest exposure quarter) and sunburn to the site (ORs of 1.8 for 3-10 and 1.5 for 11+ sunburns in a lifetime). Risk of BCC increased substantially with increasing intermittency in poor tanners but not at all in good tanners. Our data suggest that a particular amount of sun exposure delivered in infrequent, probably intense increments will increase risk of BCC more than a similar dose delivered more continuously over the same total period of time.

A population-based case-control study of sun exposure and basal cell carcinoma (BCC) was conducted in Western Australia in 1988. Its aim was to examine the relationship between risk of BCC and the amount and pattern of sun exposure. This report deals with amount of exposure. The odds ratios (ORs) for BCC on the head and neck and limbs decreased with increasing total exposure, whereas the opposite was observed for BCC on the less heavily exposed trunk, with the highest OR in those with the greatest exposure. In an analysis of all body sites together in which the total hours of exposure to the specific site was treated as a continuous variable, an initial rise in risk of BCC was seen with a peak OR of 1.4 at about 35,000 hr of exposure, followed by a fall. In contrast to these site-specific patterns, lifetime accumulated sun exposure of the whole body showed no appreciable association with BCC either in total or for working days only. Risk of BCC was positively associated with lifetime exposure on non-working days, however, with an OR for higher than baseline categories of around 1.7. There was a significant interaction between ability to tan and total and occupational sun exposure. Risk increased with increasing exposure in those who tanned well but not in those who tanned poorly. This pattern is consistent with other observations which indicate that beyond a certain level of sun exposure risk of BCC does not increase further.

Capacity to repair UV-induced DNA damage was studied by use of host cell reactivation assay in T lymphocytes isolated from 86 cases and 87 controls (aged 44-68 years) who were participants in a population-based case-control study of basal cell (BCC) or squamous cell (SCC) carcinoma of the skin in Geraldton, Western Australia. Lymphocytes were cultured and transfected with either control or UV-irradiated plasmids (254 nm, 350 J/m2) containing a reporter gene [the chloramphenicol-acetyltransferase (CAT) gene], and the repair capacity was determined by measuring CAT gene expression in protein extracts prepared from the transfected cells. DNA repair activity was 1.07 (95% confidence interval 0.94-1.26) times greater in BCC cases than in controls for each 350 J/m2 increment in UV dose to the plasmids, and 1.04 (95% confidence interval 0.85-1.26) times greater in SCC cases than in controls, though the differences were not statistically significant. DNA repair activity showed little association with age, sex and viability of the lymphocytes, though it was positively associated with their blastogenic rate (p = 0.055).

Non-melanocytic skin cancer has long been regarded as one of the harmful effects of solar ultraviolet (UV) radiation on human health. In this review, we examine epidemiologic evidence linking sun exposure and skin cancer coming from both descriptive studies in populations and analytical studies involving estimates of exposure in individuals. Particular attention is given to the quality of the published data. The epidemiologic evidence that sun exposure causes skin cancer is mainly indirect. Incidence or mortality is inversely related to latitude in populations of mainly European origin (e.g., the United States, Australia), and is higher in people born in Australia (high ambient solar radiation) than in migrants to Australia from the United Kingdom (lower ambient radiation). Skin cancer occurs mainly at sun-exposed body sites and in people who are sensitive to the sun; a reduced capacity to repair UV-induced DNA damage appears to increase the risk. The direct evidence linking sun exposure and skin cancer is weaker with few well-conducted studies of sun exposure in individuals. Mostly, studies of total sun exposure have not found statistically significant positive associations; those that did, had not adjusted for potential confounding by age and gender and thus their interpretation is limited. Studies of occupational sun exposure had relative risks not greater than 2.0; recreational exposure has been little studied. Other measurements, less direct but potentially less prone to measurement error, are sunburn (not evidently associated with skin cancer risk) and indicators of benign cutaneous sun-damage (strongly associated but lacking empirical evidence that sun exposure is their main cause). Many questions remain about the relationship between sun exposure and skin cancer.

A survey of benign melanocytic nevi was conducted among schoolchildren in Perth, Western Australia, in 1985, with the aim of describing the prevalence and causes of nevi. Children were recruited from Perth public schools that were chosen to be representative of the socioeconomic and geographic distribution of the population. Of 4,898 eligible children, 2,595 (53%) had all of their nevi counted by one member of a team of five nurses. Analysis was restricted to 2,552 children aged 5-14 years. Children of European origin (i.e., white children), who comprised the majority of the sample (2,376 children), had many more nevi than did children of other ethnic origins. Among white children, the prevalence of nevi increased progressively with age, although the number of nevi per unit of skin area reached a plateau at about 9 years of age. Boys had more nevi at all ages than did girls. The number of nevi per unit of area was highest on the lateral surfaces of the upper limbs and the face and neck, and was lowest on the lower limbs. Children whose parents had been born in Southern Europe were likely to have few nevi. Children with red hair had relatively few nevi, but children with light skin generally had more nevi than children with darker skin. Ability to tan and propensity to burn were also associated with number of nevi, although not in a simple fashion; numbers of nevi were highest in intermediate categories of these two variables. The relation with freckling was also complex; the mean number of nevi increased with increasing freckling until the freckling became moderate to heavy, after which it fell.

A survey of benign melanocytic nevi was conducted among children in Perth, Western Australia, in 1985. Children were examined by one of a team of five nurses who counted all of their nevi. Linear regression was performed on the logarithmically transformed mole counts to assess the degree of interobserver variation. Among 2,354 white children aged 5-14 years, 3.9% of the variation in numbers of nevi of all sizes and 7.7% of the variation in nevi 2 mm or more in diameter was attributed to variation among observers. The observer variation was less for the back than for any other body site. Differences between observers were greater in children with heavy freckling than in children with little or no freckling. However, the interaction between degree of freckling and observer accounted for more than 1% of the variation in counts only at sites where freckling was common (the face and neck and the upper limbs). The reproducibility of counts made by pairs of observers on 236 of the children, estimated by intraclass correlation coefficients, was 0.79 for all nevi and 0.65 for nevi 2 mm or more in diameter. The mean count of nevi on the back obtained by examining photographs of 100 children aged 8-9 years (11.9 nevi) was similar to that recorded by the examiners (12.3; p = 0.31), and the two measures were highly correlated (r = 0.89).

Many human skin tumors contain mutated p53 genes that probably result from UV exposure. To investigate the link between UV exposure and p53 gene mutation, we developed two methods to detect presumptive UV-specific p53 gene mutations in UV-exposed normal skin. The methods are based on mutant allele-specific PCRs and ligase chain reactions and designed to detect CC to TT mutations at codons 245 and 247/248, using 10 micrograms of DNA samples. These specific mutations in the p53 gene have been reported in skin tumors. CC to TT mutations in the p53 gene were detected in cultured human skin cells only after UV irradiation, and the mutation frequency increased with increasing UV dose. Seventeen of 23 samples of normal skin from sun-exposed sites (74%) on Australian skin cancer patients contained CC to TT mutations in one or both of codons 245 and 247/248 of the p53 gene, and only 1 of 20 samples from non-sun-exposed sites (5%) harbored the mutation. None of 15 biopsies of normal skin from non-sun-exposed or intermittently exposed sites on volunteers living in France carried such mutations. Our results suggest that specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation. Measurement of these mutations may be useful as a biologically relevant measure of UV exposure in humans and as a possible predictor of risk for skin cancer.

Between the early 1960s and the late 1980s, the incidence of melanoma increased at a rate of 3-7% per year in populations of mainly European origin. Corresponding trends were observed in mortality. Higher rates of increase in incidence were observed in a few populations (eg 8.9% per year in Hawaii whites). With the exception of Japan and possibly Puerto Rico, incidence rates of melanoma have remained stable in the few populations of mainly non-European origin for which reliable incidence data were available. A comparison of age specific trends in incidence and mortality in populations of mainly European origin showed two general patterns: a continuous increase in incidence in all age groups but with moderation or cessation of the previous rising trend in mortality in younger people in more recent time periods (eg Canada, continental USA, Denmark and the UK) and recent moderation or cessation of both incidence and mortality trends in younger people (eg New Zealand and, possibly, Hawaii whites). The first of these two patterns appeared to be the most common. Studies of site specific trends in incidence in 13 populations indicate that the highest rates of increase have generally been for melanomas on the trunk and the lowest for those on the head and neck. There is weak evidence to suggest that the rate of increase on the lower limbs has been greater in women than in men. Studies of incidence trends in the 1980s by thickness of melanoma in seven populations show that relative and absolute incidence has increased most for the thinnest melanomas and least for the thickest lesions. Increasing detection, earlier diagnosis and a real rise may together explain the increase in incidence of melanoma. The increases in mortality suggest that incidence has really increased, and the recent moderation in mortality trends may be explained by improved survival from melanoma due, most likely, to increasingly early diagnosis. In some populations, it may also indicate that the incidence increases are coming to an end. The disproportionately increasing incidence of thin melanoma, the divergence between incidence and mortality trends and the recent sharp increases in incidence in some populations suggest that earlier diagnosis or greater detection of less aggressive melanomas may have contributed to the incidence trends. A progressive change from predominantly occupational to predominantly recreational patterns of sun exposure is the most likely cause of increasing real incidence of melanoma in populations of mainly European origin.

Between 1986 and 1988 the annual incidence of invasive melanoma in the Hunter area of New South Wales, Australia, almost doubled to 52.5 per 100,000 in men and 42.9 per 100,000 in women. These rates have been maintained and are similar to those reported for 1987 in Queensland, Australia, which are the highest in the world. Most of the increase in incidence was in melanomas less than 1.50 mm in thickness, and adults of both sexes and all ages were affected. Thicker melanomas also increased in incidence but only in adults 45 years and older, and mainly in men. An analysis of health insurance data on treatment of skin lesions and data from a histopathology laboratory suggested that diagnosis and treatment of skin lesions generally in the Hunter area had increased almost 2-fold over this period. Advancement of the time of diagnosis and a real increase in incidence were likely explanations for some of the observed trends. Increasing diagnosis of a non-metastasising form of thin melanoma, consequent upon increasing removal of pigmented skin lesions by medical practitioners, may also explain some of the observed increase in the incidence of the disease. This possibility has important implications for proposed population screening programs, and methods are needed to distinguish such lesions, if they exist, from potentially fatal melanoma.

All patients with a diagnosis of cutaneous malignant melanoma (CMM) in Western Australia from 1980 to 1981 were observed for up to 6 years to determine vital status and to detect the development of local recurrences of the primary lesion. Approximately 35% of all patients had their tumors excised with surgical margins of less than 1 cm. When compared with patients whose tumors were excised with margins of at least 2 cm, the fatality rate in those with narrow margins was slightly less (rate ratio, 0.60; 95% confidence interval [CI], 0.20% to 1.80% for margins of 5 to 9 mm; rate ratio, 0.69; 95% CI, 0.26% to 1.87% for margins of 1 to 4 mm); however, this difference could have been caused by chance alone. The risk of local recurrence within 5 years after diagnosis was 2% (95% CI, 1% to 4%). The risk was strongly related to age and tumor thickness, but did not appear to be influenced by the width of excision (greater than 1 cm versus less than 1 cm: rate ratio, 1.03; 95% CI, 0.25% to 4.34%). The apparent lack of effect could be caused by to chance alone because the number of local recurrences was small.

Five-year survival rates were slightly higher for patients with cutaneous malignant melanoma (CMM) diagnosed in Western Australia in 1980/1981 (89% in men and 95% in women) than in those whose melanomas were diagnosed in 1975/1976 (88% in men and 91% in women). The improvement in survival was probably due to a decrease in median tumor thickness from 1.29 mm in 1975/1976 to 0.77 mm in 1980/1981 because tumor thickness was the most important histologic index of prognosis. Tumor cell type and cross-sectional profile were the only other histologic characteristics that independently influenced fatality rates. Prognosis was significantly worse in males than in females and in patients with tumors on the posterior head and neck. Ten-year survival rates of patients whose melanomas were diagnosed in 1975/1976 was 82% in men and 87% in women, indicating that these patients continued to experience some excess mortality up to 10 years after diagnosis. The comparatively small improvement in prognosis in the 5-year period between these two groups suggests that survival might be expected to continue to improve only gradually unless there is a sharp absolute decrease in the number of thick tumors diagnosed.

The roles of ethnic origin, pigmentary traits, sun sensitivity and other cutaneous characteristics as risk factors for basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) were examined in a case-control study of prevalent and incident cases of histopathologically confirmed skin cancers. Two hundred and twenty six confirmed cases of BCC, 45 of SCC and 1,015 controls with no lesions were identified in a population-based survey of skin cancer in 1987 in Geraldton, Western Australia. The risk of both cancers was higher in native-born Australians than in migrants. The risk of BCC decreased with increasing age at arrival in Australia. Southern European ancestry was strongly protective against BCC (for any southern European grandparents) and SCC (no case of SCC had any grandparents of southern European origin). Inability to tan was the strongest pigmentary risk factor for both BCC and SCC. Among factors that incorporated a measure of sun exposure as well as sun sensitivity, freckling on the arm in childhood was important for both cancers, the number of moles on the back was important for BCC, and forearm skin colour and having a permanent colour difference between the neck and adjacent protected areas were important for SCC. Among measures of sun damage to the skin, solar elastosis of the neck was a strong risk factor for both BCC and SCC, loss of fine texture of the skin of the back of the hands (as measured by cutaneous microtopography) was important for BCC and telangiectasia of the face for SCC. When all important variables for each cancer were examined together in a single model with age, sex, migrant status or age at arrival in Australia, and ethnicity, in ability to tan, solar elastosis of the neck, and the number of moles on the back were independently significant risk factors for BCC and solar elastosis of the neck and having a permanent colour difference between the neck and adjacent protected areas were independently significant risk factors for SCC. The effects of age at arrival or migrant status and ethnic origin remained important in the models incorporating these factors. A history of ever having acne and a history of warts were protective for BCC and a history of acne was protective for SCC.

A survey of the incidence and prevalence of non-melanocytic skin cancer in Geraldton, Western Australia, was undertaken in November 1987. All residents aged 40 to 64 years whose names were on the electoral roll on August 1, 1987 were invited to undergo a whole-body skin examination by a dermatologist. When a skin cancer was suspected, participants were referred for treatment to their usual medical practitioner. Subjects were asked to recall incident skin cancers over the preceding two years, and medical records were searched for confirmatory evidence. Histological confirmation of all lesions, both prevalent and incident, was sought and sections were obtained for a standardized review. The prevalence of confirmed non-melanocytic skin cancer in those aged 40 to 64 years was 7.0% in men and 4.7% in women. The prevalence of basal-cell carcinoma (BCC) was 6.5% in men and 4.5% in women while the prevalence of squamous-cell carcinoma (SCC) was 1.2% in men and 0.3% in women. The estimated incidence rate of non-melanocytic skin cancer in this age group was 1560 per 100,000 person-years. The estimated incidence rate of BCC in men was 1335 per 100,000 person-years, and in women 817 per 100,000, while in men the estimated incidence rate of SCC was 890 per 100,000 person-years, and in women it was 289 per 100,000 person-years.

Computerized video image analysis of Feulgen-stained paraffin sections was used to assess the relationships of nuclear DNA content and other nuclear morphological characteristics with survival from cutaneous melanoma. The results indicate that nuclear area and deviation from diploidy have effects on survival independent of tumor thickness and the age of the patient. Tumor thickness, however, remained the most important predictor of survival. Video image analysis of tissue sections, by virtue of its speed, simplicity, and accuracy, appears to be a potentially valuable prognostic method.