Genetic factors associated with naevus count and dermoscopic patterns: preliminary results from the Study of Nevi in Children (SONIC).

BACKGROUND: Melanocytic naevi are an important risk factor for melanoma. Naevi with distinct dermoscopic patterns can differ in size, distribution and host pigmentation characteristics. OBJECTIVES: We examined MC1R and 85 other candidate loci in a cohort of children to test the hypothesis that the development and dermoscopic type of naevi are modulated by genetic variants. METHODS: Buccal DNAs were obtained from a cohort of 353 fifth graders (mean age 10·4 years). Polymorphisms were chosen based on a known or anticipated role in naevi and melanoma. Associations between single-nucleotide polymorphisms (SNPs) and baseline naevus count were determined by multivariate regression adjusting for sex, race/ethnicity and sun sensitivity. Dermoscopic images were available for 853 naevi from 290 children. Associations between SNPs and dermoscopic patterns were determined by polytomous regression. RESULTS: Four SNPs were significantly associated with increasing (IRF4) or decreasing (PARP1, CDK6 and PLA2G6) naevus count in multivariate shrinkage analyses with all SNPs included in the model; IRF4 rs12203952 showed the strongest association with log naevus count (relative risk 1·56, P < 0·001). Using homogeneous naevi as the reference, IRF4 rs12203952 and four other SNPs in TERT, CDKN1B, MTAP and PARP1 were associated with either globular or reticular dermoscopic patterns (P < 0·05). CONCLUSIONS: Our results provide evidence that subsets of naevi defined by dermoscopic patterns differ in their associations with germline genotypes and support the hypothesis that dermoscopically defined subsets of naevi are biologically distinct. These results require confirmation in larger cohorts. If confirmed, these findings will improve the current knowledge of naevogenesis and assist in the identification of individuals with high-risk phenotypes.

Clinical and dermoscopic characteristics of new naevi in adults: results from a cohort study.

BACKGROUND: Naevogenesis is a process known to occur throughout life. To date, investigators have made conclusions about new naevi in adults based on results of cross-sectional studies. OBJECTIVES: To determine the incidence of new naevus development in adults and to describe the dermoscopic morphology of new naevi. METHODS: A cohort of 182 patients seen at the outpatient dermatology clinic at Memorial Sloan-Kettering Cancer Center between 2000 and 2009 was evaluated with baseline total body photographs. The patients were aged 17 years or older and had presented for routine follow-up surveillance examination at least 3 months after baseline total body photographs. The number of new naevi and the dermoscopic morphology of these naevi were recorded. RESULTS: Of the 182 patients evaluated, 50 (27%) developed at least one new naevus during follow-up. The incidence of new naevi was 202 per 1000 person-years of follow-up. The most common types of naevi were reticular (47·1%), followed by the homogeneous (22·1%) and complex (reticuloglobular) patterns (15·4%). CONCLUSIONS: Our results provide support for the theory that there are two distinct pathways of naevogenesis, a dynamic process occurring throughout life. This study demonstrates that the predominant dermoscopic morphology of newly acquired naevi in adults is reticular.

Heartburn risk factors, knowledge, and prevention strategies: a population-based survey of individuals with heartburn.

BACKGROUND: Twenty-five million adults experience heartburn daily. To target individuals for prevention programs, characteristics of persons with heartburn and the associated causes of this condition must first be identified. METHODS: We conducted a population-based telephone survey of 2000 individuals with heartburn to describe the cause of the disease, knowledge of risk factors, and prevention strategies. RESULTS: Lifestyle and work habits, and certain food and beverage consumption, were associated with heartburn. Women reported the onset of heartburn about 5 years later than men. Survey respondents were unaware of the risk factors for heartburn, and sex-dependent differences in knowledge were apparent. Logistic regression modeling identified increasing age, female sex, higher level of education, and frequent vs infrequent heartburn as significant (P<.02) predictors of whether patients told a physician about their heartburn symptoms. Increasing age, higher body mass index, and reduced level of education were significant (P<.02) predictors of frequent vs infrequent heartburn in this study population. CONCLUSION: The findings of this study provide a framework for the development of a heartburn prevention program based on lifestyle modification.

Parent-child relationships in nutrient intake: the Framingham Children's Study.

Nutrient intake affects many of the identified risk factors for coronary heart disease (CHD). Although CHD risk factors have been shown to aggregate within families, less is known about the familial aggregation of nutrient intake. We analyzed diet records for an average of 9 d per subject on 87 mothers, 83 fathers, and 91 children aged 3-5 y. A statistically significant but modest correlation (r less than 0.50) was found between parents' and children's intakes for most nutrients. The intake of nutrients was more strongly related between mothers and children than between fathers and children, and there was a stronger association with children's values for parents consuming more meals at home. The results of this study confirm that parents' eating habits have an impact on the nutrient intake of their preschool children; the study furnishes indirect support for dietary-intervention programs targeting families for the primary prevention of CHD.

Evaluation of factors associated with skin self-examination.

Early detection and excision of thin lesions may be important in reducing mortality from melanoma. Periodic skin self-examination may be beneficial in identifying thin lesions. The purpose of this study was to evaluate factors associated with skin self-examination. The study population was comprised of 549 Caucasian residents of Connecticut 18 years of age or older who were selected as controls as part of a population-based case-control study on skin self-examination and melanoma conducted during 1987-1989. Personal interviews were conducted to obtain information on skin self-examination, demographics, history of cancer, phenotypic characteristics, sun exposure habits, and screening and health behaviors. Nevus counts were performed by trained nurse interviewers. Logistic regression was used to model the relationship between the variables of interest and skin self-examination. Female gender was identified a priori as a predictor of skin self-examination, and thus all analyses were stratified by gender. Age, education, and marital status were also identified a priori as important predictor variables and were selected for inclusion in the final models. Skin awareness was a strong factor associated with skin self-examination for both females and males. For females, previous benign biopsy or the presence of an abnormal mole was identified as important for future skin self-examination using our criteria. A family history of cancer, physician examination, and change in diet to reduce cancer risk increased the likelihood of skin self-examination in males but not females. In women, light hair color may increase the likelihood of performing skin self-examination. Older age and college or postgraduate education was associated with a decreased likelihood of performing skin self-examination in both males and females. Identifying factors associated with skin self-examination will enable health care providers to target individuals who may not be performing skin self-examination but who are at increased risk for developing melanoma.

Signs and symptoms of melanoma in older populations.

We conducted a descriptive study to assess the relationship between increasing age and the reporting of melanoma signs/symptoms in 634 hospital-based and 624 population-based incident cases of melanoma. Multivariate logistic regression was used to evaluate the relationship between older age (> or = 50 years) and the reporting of melanoma signs/symptoms. Older patients were less likely to report itching and change in elevation of their lesions (P < 0.05). Change in color was also less likely to be reported by older patients, although not statistically significant. Ulceration of the lesion was reported significantly more by older patients (P < 0.05). Older individuals may be less likely to report itching and change in elevation/color of their lesions, but more likely to report ulceration, a symptom associated with advanced disease and poor prognosis. Further research is necessary to provide a better understanding of the development of melanoma in older populations so that new strategies can be explored to improve early detection in this age group.

Factors encouraging cohort maintenance in a longitudinal study.

Maintenance of the cohort is one of the primary challenges of a longitudinal study. At the end of 3 years of follow up in the Framingham Children's Study, a longitudinal study of young children and their parents, 100 of the original 106 families (94.3%) have remained in the study. A questionnaire was administered to identify factors contributing to the high rate of follow up to this point in the study. The attitudes of the staff, feedback to the subjects, the staff's handling of questions and problems, and association with the Framingham Heart Study emerged as the most important factors influencing continued participation in the study. In addition, 99% of the subjects stated that they believed the medical research to be important. We conclude that the quality of the communication with study participants and the subjects' perceived importance of the research have been the key factors in maintaining the cohort in this longitudinal epidemiologic study.

Patient knowledge, awareness, and delay in seeking medical attention for malignant melanoma.

We investigated the relationship between patient knowledge, awareness, and delay in seeking medical attention for melanoma. The study population was comprised of 255 cases with cutaneous melanoma newly diagnosed during January 15, 1987 to May 15, 1989, who were part of a population-based case control study. Personal interviews were conducted to obtain information on patient's knowledge of melanoma signs and symptoms, skin awareness, delay in seeking medical attention, and related covariates. The adjusted odds ratio for the association between skin awareness and delay was 0.30 (95% confidence interval 0.12-0.71). Odds ratios ranged from 0.43 to 0.81 for knowledge and delay. Awareness of skin changes was associated with a reduced Breslow depth for stage I melanomas. Individuals who are aware of skin changes and abnormalities appear to be less likely to delay seeking medical attention for melanoma. Knowledge of melanoma signs and symptoms may also contribute to a decreased delay in melanoma diagnosis.

Estrogen replacement therapy and urinary tract infections in postmenopausal women aged 45-89.

OBJECTIVE: An elevated risk of urinary tract infections (UTIs) in postmenopausal women has been attributed to an increase in the vaginal pH. Estrogen replacement therapy (ERT) helps restore the vaginal milieu and may have a beneficial effect on risk of infection. Studies examining the association between ERT and UTIs have been inconsistent. We conducted a nested case control study to clarify this relationship in women aged 45-89. DESIGN: For each case, we selected up to five control women, matched by year of birth. We used pharmacy records to classify women as new users, past users, ongoing users (past and new users), and never users of ERT. There were 254 cases and 1,268 controls. RESULTS: The risk ratio for UTI was 1.02 [95% confidence interval (CI) 0.74, 1.40] for any use versus never use, after adjustment for health care utilization. The risk ratio for the association between new use and UTI was 1.13 (95% CI 0.46, 2.77). For ongoing users the risk ratio was 1.08 (95% CI 0.76, 1.54), whereas the risk ratio for past use was 0.77 (95% CI 0.39, 1.48). CONCLUSIONS: Our results do not support a protective effect of ERT on the risk of UTIs.

The epidemiology of physical activity and cancer.

Experimental studies in animals and epidemiological studies in human populations support an inverse association between exercise and the development of cancer. Physical activity has been shown to be protective against the development of breast and colon cancer and may also be important for other kinds of cancer such as that of the prostate. The proposed biological mechanisms for the physical activity--cancer association include exercise's effect on immune function, transit time of digestion, hormones, and body fat. There has been little research on physical activity and the effect on progression of cancer, although there are studies to suggest that it may slow the clinical course of the disease. Furthermore, exercise may be beneficial in the treatment of cancer through mood elevation, decreased loss of lean tissue, and increased quality of life. Much is still to be learned about the effect of exercise on cancer. The intensity, duration, frequency, and type of exercise that is relevant need to be clarified. As well, the time period during life when exercise is important has not been determined. It seems reasonable to conclude that exercise, a modifiable risk factor, is beneficial in preventing certain forms of cancer. Public health interventions may hold promise for cancer prevention.

Using nurse practitioners for skin cancer screening: a pilot study.

BACKGROUND: Skin cancer screening has the potential to detect early precancerous lesions and may ultimately be important in reducing melanoma mortality. The purpose of this study was to evaluate the ability of trained nurse practitioners to accurately identify suspicious lesions in a clinical setting. METHODS: We identified five nurse practitioners who had no previous experience in evaluating skin lesions. Each nurse practitioner participated in a training program for skin cancer detection consisting of a workshop, clinical apprenticeship, and didactic lectures. RESULTS: Evaluation of nurse practitioner competency involved three assessments. First, the nurse practitioner's ability to distinguish benign and malignant lesions was assessed using clinical color slides. The sensitivity of all five nurse practitioners to refer benign and malignant lesions for dermatologic follow-up based on the slides was 100%, whereas the specificity ranged from 53% to 100%. Second, each nurse practitioner evaluated approximately 25 different patients along with a single dermatologist. The nurse practitioner's ability to correctly refer patients with suspicious lesions for dermatologic follow-up was determined based on the dermatologist's assessment of need for referral. Results suggested a referral sensitivity and specificity ranging from 67% to 100% and 62% to 100%, respectively. In the final clinical assessment, 30 patients were independently examined by two dermatologists and four nurse practitioners. Using the consensus clinical diagnosis of the dermatologists as the gold standard, the nurse practitioner's sensitivity for detecting significant skin cancer lesions ranged from 50% to 100% and the detection specificity was 99% to 100%. CONCLUSIONS: These preliminary results have important implications for skin cancer screening efforts and suggest that nurse practitioners can be trained to accurately identify and triage suspicious lesions.

Is exercise beneficial in the prevention of prostate cancer?

Prostate cancer is the most frequently diagnosed cancer in men. Exercise has been studied as an alterable risk factor that may reduce the incidence, morbidity and mortality due to this cancer. Epidemiological studies play an important role in assessing the relationship between physical activity and prostate cancer. Studies have attempted to estimate physical activity level by measuring time spent in sports, leisure or occupational activity. We identified 17 studies that assessed the effect of exercise on the development of prostate cancer. Although methodological limitations could be identified in most of the studies, 9 suggested that exercise may be beneficial in decreasing prostate cancer risk, while 5 were null providing no conclusive evidence and 3 actually showed an increased risk of prostate cancer with increased physical activity. The bulk of the evidence at this time does not seem to support an overwhelmingly beneficial effect of exercise on prostate cancer risk. Future studies need to investigate the frequency, intensity and duration of physical activity as well as the type of activity and period during a man's lifetime when exercise might be beneficial. It is reasonable to conclude that exercise may be a potential factor that can be modified to prevent prostate cancer and it seems prudent to recommend that all men become physically active.

Use of and beliefs about dermoscopy in the management of patients with pigmented lesions: a survey of dermatology residency programmes in the United States.

Dermoscopy is a non-invasive technique that can be utilized for the clinical diagnosis of pigmented lesions. The aim of this study was to assess the utilization and beliefs about the usefulness of dermoscopy in the evaluation of pigmented lesions by physicians in dermatology residency programmes, and to determine the extent of dermoscopy training received by residents in these programmes. Questionnaires were sent to the directors of all the accredited dermatology residency programmes in the United States (n = 105). A follow-up postcard questionnaire was sent to the chief resident of all the responding programmes. Eighty-three physicians responded to the questionnaire (79%). Fifty-one per cent of the respondents (n = 42) reported utilizing dermoscopy. Reported reasons for using dermoscopy by respondents included the fact that it helps detect melanoma early (74%), leads to fewer biopsies (74%) and reduces patient anxiety (64%). Lack of training (51%) and lack of usefulness (42%) were amongst the reported reasons for not utilizing dermoscopy. Sixty-seven per cent of respondents reported an increase of approximately 50% in the use of dermoscopy over the past 5 years, and 45% anticipated an increase in use over the next 5 years. Thirty-eight per cent of chief residents from the responding programmes reported receiving training in dermoscopy during residency. In conclusion, half of the dermatology residency programmes currently use dermoscopy in the evaluation of pigmented lesions. The main reason for not using dermoscopy was a lack of training. Respondents anticipated a future increase in the use of dermoscopy.

Use of and beliefs about baseline photography in the management of patients with pigmented lesions: a survey of dermatology residency programmes in the United States.

Medical photography is often used in dermatology to aid in the clinical surveillance of patients with pigmented lesions. This study aimed to assess the utilization, logistics, rationale and beliefs about the usefulness of baseline photography in patients with pigmented lesions by physicians in dermatology residency programmes, and to compare current utilization to that reported in the last decade. Questionnaires were mailed to directors of all accredited dermatology residency programmes in the United States (n = 105). Eighty-three physicians responded to the questionnaire (79%). Utilization of total body and individual lesion photography was reported by 63% and 75% of the respondents, respectively; 16% of the respondents did not use any method of photography. Reasons for using photography included the following beliefs: that it helps detect early melanoma, it results in fewer biopsies, and it reduces patient anxiety. Financial and logistical constraints were reasons why some programmes were not utilizing photography. Thus baseline photography is currently used in a majority of academic dermatology programmes as an aid in the early detection of melanoma.

The association between cardiorespiratory fitness and prostate cancer.

We conducted a prospective study to assess the association between cardiorespiratory fitness and prostate cancer. The subjects were men, aged 20-80 yr, who received a preventive medical exam at the Cooper Clinic in Dallas, TX, during 1970-1989 and provided information on cardiorespiratory fitness and prostate cancer (N = 12,975). Cardiorespiratory fitness was assessed at a baseline examination between 1971 and 1989 using a maximal exercise treadmill test. Questionnaires were mailed to the men in 1982 and 1990 to ascertain incident cases of prostate cancer. Ninety-four cases of incident prostate cancer were identified. Higher cardiorespiratory fitness levels were inversely associated with the probability of development of incident prostate cancer after controlling for age, body mass index, and smoking habits; adjusted estimates of the incidence rate ratio declined from 1.1 (95% CI 0.63-1.77) to 0.73 (95% CI 0.41-1.29) to 0.26 (95% CI 0.10-0.63) across increasing quartiles of fitness (P for trend < 0.004). This protective effect was limited to participants < 60 yr old. Also, an inverse association was observed between physical activity and prostate cancer. Compared with expending < 1000 kcal.wk-1, participants who expended 1000- < 2000, 2000- < 3000, or > or = 3000 kcal.wk-1 had adjusted incidence rate ratios of 0.37 (95% CI 0.17-0.79), 0.62 (95% CI 0.27-1.41), and 0.37 (95% CI 0.14-0.98), respectively. The results suggest that cardiorespiratory fitness and physical activity levels may protect against the development of incident prostate cancer.

Complex dermoscopic pattern: a potential risk marker for melanoma.

BACKGROUND: Dysplastic naevi have repeatedly been shown to be an independent risk factor for melanoma; however, risk estimates vary. Dermoscopy has allowed for more elaborate classification of naevi based on global patterns. OBJECTIVES: To assess dermoscopic images of naevi from patients with melanoma and controls to explore dermoscopic patterns that are associated with melanoma risk. METHODS: Dermoscopic images of naevi from the backs of 20 patients with melanoma and 20 age- and sex-matched controls were reviewed for dermoscopic patterns and structures. An unblinded review of 187 naevi of patients and 150 naevi of controls was completed. Complex global dermoscopic pattern was defined in naevi presenting both network and globules, with or without structureless areas. RESULTS: Complex global dermoscopic pattern was observed more frequently in melanoma patients than controls (odds ratio, OR 2.9, P = 0.003). As for specific dermoscopic structures, presence of globules was observed more frequently in patients than controls (OR 2.3, P = 0.0001), whereas presence of dots was inversely associated with case status (OR 0.5, P = 0.002). CONCLUSIONS: These pilot data suggest that dermoscopic pattern may serve as a more robust and specific marker of melanoma risk than clinical naevus phenotype.

Dermoscopic patterns of naevi in fifth grade children of the Framingham school system.

BACKGROUND: Childhood is a critical period for naevogenesis. OBJECTIVE: To describe the prevalence of dermoscopic patterns of naevi using cross-sectional data from a population-based cohort of children. METHODS: We obtained overview digital photography of the back of fifth graders (age 10-11 years) from all 10 schools in Framingham, MA, U.S.A. From each participant, dermoscopic images of up to four naevi were obtained, including the largest and one randomly selected naevus on the upper back and a corresponding pair from the lower back. RESULTS: The study included 443 children, 61% boys, with 1181 back naevi analysed. Globular pattern was seen in 37% of naevi, reticular pattern in 13%, homogeneous pattern in 44% and complex (reticular-globular) dermoscopic pattern in 5%. Globular naevi were significantly more frequent and larger on the upper than the lower back. There was a significant hierarchic trend in naevus diameter by dermoscopic pattern: complex naevi (4.3 mm)>globular (3.3 mm)>reticular (3.0 mm)>homogeneous (2.8 mm). Reticular naevi were more prevalent in children with darker pigment phenotype (P<0.0001). There was a decrease in the size of naevi in children with darker pigmentation (P<0.0001). CONCLUSIONS: An interrelationship was observed in childhood between dermoscopic pattern, naevus size, anatomical location on the back and pigment phenotype.

Sun exposure and risk of melanoma.

BACKGROUND: As skin cancer education programmes directed to children and adolescents continue to expand, an epidemiological basis for these programmes is necessary to target efforts and plan for further evaluation. AIMS: To summarise the epidemiological evidence on sun exposure during childhood and adolescence and melanoma risk. METHODS: A literature review was conducted using Medline (1966 to December 2004) to identify articles relating to sun exposure and melanoma. The review was restricted to studies that included sun exposure information on subjects 18 years of age or younger. RESULTS: Migrant studies generally indicate an increased melanoma risk in individuals who spent childhood in sunny geographical locations, and decreasing melanoma risk with older age at arrival. Individuals who resided in geographical locations close to the equator or close to the coast during childhood and/or adolescence have an increased melanoma risk compared to those who lived at higher latitudes or never lived near the coast. The intermittent exposure hypothesis remains controversial; some studies indicate that children and adolescents who received intermittent sun exposure during vacation, recreation, or occupation are at increased melanoma risk as adults, but more recent studies suggest intermittent exposure to have a protective effect. The majority of sunburn studies suggest a positive association between early age sunburn and subsequent risk of melanoma. CONCLUSION: Future research efforts should focus on: (1) clarifying the relation between sun exposure and melanoma; (2) conducting prospective studies; (3) assessing sun exposure during different time periods of life using a reliable and quantitative method; (4) obtaining information on protective measures; and (5) examining the interrelations between ability to tan, propensity to burn, skin type, history of sunburns, timing and pattern of sun exposure, number of nevi, and other host factors in the child and adolescent populations.

Clinical and dermoscopic changes in common melanocytic nevi in school children: the Framingham school nevus study.

BACKGROUND: Nevi are potential precursors of malignant melanoma and are important risk factors for the development of the disease. Childhood may be a critical time for the formation and evolution of nevi. OBJECTIVES: To document the development of new nevi and to document the clinical and dermoscopic changes in index nevi in school children during a 1-year follow-up. METHODS: Digital photographs and dermoscopic images of the back of subjects were compared at baseline and 1-year follow-up to assess changes in nevi counts and in clinical and dermoscopic features of index nevi. RESULTS: Overall participation rate was 81% (42/52). 56.4% of study participants were found to have an increased number of nevi at 1-year follow-up. All nevi were small and clinically insignificant. Fifty percent of study participants were found to have dermoscopic changes in their index nevi at 1-year follow-up. Eighty-five percent of these changes were classified as subtle and 15.0% as obvious. CONCLUSIONS: A significant portion of students developed new nevi over the course of 1 year. Most index nevi remained stable in pattern and structure. Benign dermoscopic changes occurred in 50.0% of index nevi. However, none of the dermoscopically changed nevi revealed any major changes and the overall nevus pattern remained unchanged. The relevance of these changes is uncertain and further follow-up may elucidate their significance.