Risk factors of incident melanocytic nevi: a longitudinal study in a cohort of 1,232 young German children

The number of melanocytic nevi is the most important independent risk factor for cutaneous melanoma. Aim of our study was to add information to the controversial discussion on the role of chronic-moderate and intermittent-high sun exposure and sunburns for the development of melanocytic nevi by the use of a large longitudinal study. A longitudinal study with a 3-year follow-up was conducted in 1,232 young children 2-7 years of age attending 78 public nursery schools in Bochum and Stuttgart, Germany. Total body nevus counts, assessment of pigmentary features and nevus counts on arms of parents were carried out. Parents underwent a standardized interview concerning sun exposure, sunburns and sun-protective behavior. Applying multiple linear regression analysis higher numbers of incident nevi were associated with host factors like light skin complexion (skin Type II vs. IV, p = 0.022) and freckling of the face (p < 0.001), with parental factors like nevus counts on mothers' (p < 0.001) and fathers' (p = 0.004) arms and at least one parent being of German descent (p = 0.006), and with environmental factors like intermittent-high sun exposure during holidays (p < 0.001) and chronic-moderate ultraviolet radiation at home (p = 0.007). Sunburns were a significant risk factor for nevus development (p = 0.005). Total cumulative sun exposure seems to be the crucial environmental risk factor for the development of nevi, whether the child is exposed to chronic-moderate or intermittent-high ultraviolet light doses. Public health education should focus primarily on avoiding sun exposure especially in children with fair skin and parents with high nevus counts.     

A murine model for the development of melanocytic nevi and their progression to melanoma

Acquired melanocytic nevi are commonly found in sun exposed and unexposed human skin, but the potential for their transformation into invasive melanoma is not clear. Therefore, a mouse model of nevus initiation and progression was developed in C3H/HeN mice using a modified chemical carcinogenesis protocol. Nevi develop due to DNA damage initiated by dimethylbenz(a) anthracene (DMBA) followed by chronic promotion with 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Dysplastic pigmented skin lesions appeared in 7–9 wk with 100% penetrance. Nests of melanocytic cells appeared in a subset of skin draining lymph nodes (dLN) by 25 wk, but not in age matched controls. Immunohistochemistry, real‐time PCR, and flow cytometric analyses confirmed their melanocytic origin. Transformed cells were present in a subset of nevi and dLNs, which exhibited anchorage‐independent growth, tumor development, and metastasis in nude mice. Approximately 50% of the cell lines contained H‐Ras mutations and lost tumor suppressor p16^Ink4a expression. While most studies of melanoma focus on tumor progression in transgenic mouse models where the mutations are present from birth, our model permits investigation of acquired mutations at the earliest stages of nevus initiation and promotion of nevus cell transformation. This robust nevus/melanoma model may prove useful for identifying genetic loci associated with nevus formation, novel oncogenic pathways, tumor targets for immune‐prevention, screening therapeutics, and elucidating mechanisms of immune surveillance and immune evasion. © 2015 The Authors. Molecular Carcinogenesis, published by Wiley Periodicals, Inc.     

Sun exposure and the incidence of melanocytic nevi in young Australian children

The number of melanocytic nevi (MN) is an important risk factor for cutaneous melanoma. The present study further investigated the relationship between sun exposure, the incidence of MN, and the prevalence of large acquired MN (>or=5 mm). A cohort of 479 preschool children born in Townsville, Australia was examined for MN in 1991 and a year later. Sun exposure was assessed by questionnaire. The erythemally effective dose of solar UV radiation was estimated from questionnaire data combined with local UV biometry. Almost all (97.7%) children had acquired new MN (median, 12), with a median incidence rate of 11.0 per year (interquartile range, 7.0-16.5). Total number of hours of sun exposure during follow-up (P = 0.034) and tendency to burn (P = 0.028) were independent risk factors for MN incidence. Sunburn experience during follow-up failed to reach significance when adjusted for tendency to burn. Lifetime number of sunburns (P < 0.001) and the severity of sunburns experienced during follow-up (P < 0.001) were significantly related to the presence of large acquired MN at follow-up. Reducing the total number of hours of sun exposure is particularly relevant in sun-sensitive children and may restrain the development of MN, whereas avoiding sunburn in young children might prevent large MN, subsequently reducing the risk of melanoma.     

Reduced sun exposure and tanning in children after 2 years of a school-based intervention (Australia)

Objective: This paper presents the results of the evaluation of measured suntan and parent-reported sun exposure in participating children after 2 years of the Kidskin study, a 5-year school-based sun protection intervention undertaken in Perth, Western Australia (1995–1999). Methods: The study involves three groups: a control, a moderate, and a high intervention group. Participants were 5 or 6 years of age at the beginning of the study. Control schools received the standard Health Education curriculum, while intervention schools received a multicomponent intervention including a specially designed curriculum. Children in the high intervention group also received program materials over the summer vacation and were offered sun-protective swimwear at low cost. At the end of the second summer, suntan was measured and parents completed a questionnaire about their child's sun-related behavior. Results: Children in the intervention groups – especially the high group – were less tanned at the end of the summer; this effect was greater for the back than for the forearms. These children were also reported to have received less sun exposure and made greater use of sun protection measures. Conclusion: Intensive school-based interventions can reduce tanning and reported sun exposure in children.     

Moderate sun exposure and nevus counts in parents are associated with development of melanocytic nevi in childhood: a risk factor study in 1,812 kindergarten children

BACKGROUND: Melanocytic nevi have been identified as the most important risk factor for cutaneous melanoma. Sun exposure, sunburns, and light pigmentation have been found to be associated with their development in childhood. To the authors' knowledge, nevus proneness of parents and the exact type of ultraviolet (UV) exposure have not yet been investigated in this context. The authors' objective was to determine independent risk factors and their impact for nevus development in childhood. METHODS: The current study was conducted by two university departments of dermatology in 49 public nursery schools in Stuttgart, Germany and in 38 public nursery schools in Bochum, Germany. The cross-sectional study included 1,812 children aged 2-7 years and their parents. Total body nevus counts in children, assessment of pigmentary features, and nevus counts on the arms of parents were performed. Parents underwent a standardized interview concerning national origin and lifestyle features, as well as habits and magnitude of sun exposure of children. Analysis was performed by multivariate linear regression analysis and by multiple logistic regression analysis. RESULTS: The number of nevi was found to steadily increase with age from a median of 3 at age 2 years to 19 at age 7 years (P < 0.0001). High numbers of nevi in children were associated with the number of weeks on sunny holidays, outdoor activities at home, skin type, facial freckling, ethnicity of parents, and the number of nevi on the arms of parents. Previously experienced sunburns failed significance (P = 0.0620). CONCLUSIONS: The authors found a strong association between nevus development in children and the number of parental moles, which most likely points to an inherited factor. Moderate sun exposure such as outdoor activities during a German summer without sunburns seemed to be sufficient for induction of melanocytic nevi. The authors believe that these findings will have direct impact on concepts for preventive strategies.     

Impact of a primary care intervention on smoking, drinking, diet, weight, sun exposure, and work risk in families with cancer experience

Background

Modifying multiple behavior risks is a promising approach to reduce cancer risk. Primary prevention advices of the European Code against Cancer were included in an educational intervention (EI) using social cognitive theories for motivating families with cancer experiences to adopt six cancer prevention behaviors.

Methods

A randomized clinical controlled trial recruited 3,031 patients from Primary Care among cancer patients’ relatives. The experimental group (EG) received four EI, one EI every six months, focused on tobacco, alcohol, diet, weight, sun and work, and based on social cognitive models. The impact of the first three EI was calculated measuring at baseline and 18 months later: (a) The percentage of people with each risk behavior; (b) The score reached in a Total Cancer Behavioral Risk (TCBR) indicator; (c) The Odds Ratios at the post-test.

Results

Five risk behaviors decreased significantly more (p < 0.01) in the EG than in the CG: Smoking (OR = 0.662), drinking (OR = 0.504), diet (OR = 0.542), weight (OR = 0.698), and sun (OR = 0.389). The TCBR indicator also decreased an average of nearly 5 points (28.42 vs. 23.82), significantly more (p < 0.001) in the EG.

Conclusion

Families with cancer experiences changed five cancer risk behaviors when approached in Primary Care with interventions based on social cognitive models.     

国产盐酸托烷司琼与欧必亭防治化疗所致恶心、呕吐的比较研究

目的观察国产盐酸托烷司琼防治化疗所致的恶心、呕吐的疗效及其不良反应。方法采用随机对照方法,将49例肿瘤患者随机分为A(n=25)、B(n=24)2组,在使用顺铂(DDP)或阿霉素(ADM)化疗前,A组给予5mg国产盐酸托烷司琼缓慢静脉推注,B组给予5mg进口盐酸托烷司琼(欧必亭),2组用法相同。在化疗后7d内观察化疗所致胃肠道反应和止呕药的不良反应。结果A组急性恶心的完全控制率为48.0%,B组为47.8%(P>0.05);A组急性呕吐的完全控制率为80.0%,B组为65.2%(P>0.05)。A组和B组延迟性恶心和呕吐反应无显著差异(P>0.05)。2组患者对不同止吐方案耐受性良好,不良反应发生率无差别(P>0.05)。结论国产盐酸托烷司琼用于防治化疗所致恶心、呕吐安全有效。     

Relation of childhood brain tumors to exposure of parents and children to tobacco smoke: the SEARCH international case-control study. Surveillance of Environmental Aspects Related to Cancer in Humans

The etiology of childhood brain tumors (CBTs) remains unknown. Tobacco smoke contains several known carcinogens and can induce DNA adducts in human placenta and hemoglobin adducts in fetuses. We present the results of an international case-control study to evaluate the association between CBTs and exposure of parents and children to cigarette smoke. The study was undertaken as part of the SEARCH program of the IARC. Nine centers in 7 countries were involved. The studies mainly covered the 1980s and early 1990s. Cases (1,218, ages 0-19 years) were children newly diagnosed with a primary brain tumor; there were 2,223 population-based controls. Most mothers who agreed to participate were interviewed in person at home. Odds ratios (ORs) were calculated by unconditional logistic regression, adjusted for age, sex and center, for all types of CBT combined, 4 CBT histotypes, 5 age groups and each center. There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life. These results did not change considering the child's age at diagnosis, the histologic type of tumor or center.     

Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow‐up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non‐significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non‐aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.     

Genetic determinants of cytochrome P450 2A6 activity and biomarkers of tobacco smoke exposure in relation to risk of lung cancer development in the Shanghai cohort study

Cytochrome P450 2A6 (CYP2A6) catalyzes nicotine metabolism and contributes to the metabolism of the tobacco‐specific lung carcinogen, NNK. Genetic variation in CYP2A6 may affect smoking behavior and contribute to lung cancer risk. A nested case–control study of 325 lung cancer cases and 356 controls was conducted within a prospective cohort of 18,244 Chinese men in Shanghai, China. Quantified were 4 allelic variants of CYP2A6 [*1(+51A), *4, *7, and *9] and urinary total nicotine, total cotinine, total trans‐3'‐hydroxycotinine (3HC) and total NNAL (an NNK metabolite). Calculated were total nicotine equivalents (TNE), the sum of total nicotine, total cotinine and total 3HC and the total 3HC:total cotinine ratio as a measure of CYP2A6 activity. The nicotine metabolizer status (normal, intermediate, slow and poor) was determined by CYP2A6 genotypes. The smoking‐adjusted odds ratios (95% confidence intervals) of lung cancer for the highest vs lowest quartile of total nicotine, total cotinine, total 3HC, TNE and total NNAL were 3.03 (1.80–5.10), 4.70 (2.61–8.46), 4.26 (2.37–7.68), 4.71 (2.61–8.52), and 3.15 (1.86–5.33) (all P_trend < 0.001), respectively. Among controls CYP2A6 poor metabolizers had a 78% lower total 3HC:total cotinine ratio and 72% higher total nicotine (P_trend ≤ 0.002). Poor metabolizers had an odds ratio of 0.64 (95% confidence interval = 0.43–0.97) for lung cancer, which was statistically nonsignificant (odds ratio = 0.74, 95% confidence interval = 0.48–1.15) after adjustment for urinary TNE and smoking intensity and duration. The lower lung cancer risk observed in CYP2A6 poor metabolizers is partially explained by the strong influence of CYP2A6 genetic polymorphisms on nicotine uptake and metabolism.