The importance of motivation in selecting undergraduate medical students for extracurricular research programmes

IntroductionExtracurricular research programmes (ERPs) may contribute to reducing the current shortage in physician-scientists, but usually select students based on grades only. The question arises if students should be selected based on their motivation, regardless of their previous academic performance. Focusing on grades and lacking to take motivation into account when selecting students for ERPs might exclude an important target group when aiming to cultivate future physician-scientists. Therefore, this study compared ERP students with lower and higher previous academic performance on subsequent academic performance, ERP performance, and motivational factors. MethodsProspective cohort study with undergraduate medical students who filled in a yearly questionnaire on motivational factors. Two student groups participating in an ERP were compared: students with first-year grade point average (GPA) >= 7 versus = 7 group. However, there was no significant between-group difference on in-time bachelor completion and the = 7 group in terms of intrinsic motivation for research, perceptions of research, and curiosity. ConclusionsSince intrinsic motivation for research, perceptions of research, and curiosity are prerequisites of future research involvement, it seems beneficial to focus on motivation when selecting students for ERPS, allowing students with lower current academic performance to participate in ERPs as well.Dermatology-oncolog

GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi

Dermatology-oncolog

GNAQ and GNA11 mutations and downstream YAP activation in choroidal nevi

Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells

Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods. Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer dev

The effect on melanoma risk of genes previously associated with telomere length.

Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/jnci/dju26

The absence of multiple atypical nevi in germline CDKN2A mutations: Comment on "Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome''

Dermatology-oncolog

The role of MC1R gene variants and phenotypical features in predicting high nevus count

Variants in the Melanocortin 1 Receptor (MC1R) gene have been associated with an increased risk of melanoma, but the role in nevus count is unclear. We investigated if specificMC1Rgene variants or the number ofMC1Rgene variants and phenotypical features were associated with nevus count. A total of 494 participants of the 'Leiden skin cancer study' were included and the MC1R gene coding sequence was analysed by single-strand conformation polymorphism analysis followed by sequencing of unknown variants. The association betweenMC1Rgene variants and nevus count and the association between age, gender and phenotypical features and nevus count were studied using the Chi-square test. Study of nine frequently occurringMC1Rgene variants in participants without skin cancer (n = 203) showed that the 'r' Val60Leu variant was significantly associated with high nevus count (>50 nevi) (P = 0.017). This association was very strong among women (P < 0.001), but not present among men. Having one or twoMC1Rvariants in general did not show a significant difference in the nevus count. Hair colour, skin type, eye colour and age were not significantly associated with nevus count, whereas gender showed a significant association (P = 0.008), with the highest nevus counts in female. The Val60Leu variant of the MC1R gene could be a promising candidate as an independent predictor of high nevus count, particularly in women. This information about the genetic makeup could promote personalized follow-up strategies and might help to prevent skin cancer in the future.Dermatology-oncolog

Acquired Melanocytic Nevi in Childhood and Familial Melanoma

Development and application of statistical models for medical scientific researc

Clinical and histologic characteristics of malignant melanoma in families with a germline mutation in CDKN2A

Background: About 10% of cutaneous malignant melanomas (CMM) occur in individuals with a family history of melanoma. In 20% to 40% of melanoma families germline mutations in CDKN2A are detected. Knowledge of the clinicohistologic characteristics of melanomas and patients from these families is important for optimization of management strategies, and may shed more light on the complex interplay of genetic and environmental factors in the pathogenesis of melanoma. Objective: We sought to investigate the clinical and histologic characteristics of CMM in CDKN2A-mutated Methods: Clinical and histologic characteristics of 182 patients with 429 CMM from families with a founder mutation in CDKN2A (p16-Leiden mutation) were compared with 7512 patients with 7842 CMM from a population-based cancer registry. Results: Patients with p16-Leiden had their first melanoma 15.3 years younger than control patients. The 5-year cumulative incidence of second primary CMM was 23.4% for patients with p16-Leiden compared with 2.3% for control patients. The risk of a second melanoma was twice as high for patients with p16-Leiden who had their first melanoma before age 40 years, compared with older patients with p16-Leiden. Unlike control patients, there was no body site concordance of the first and second melanoma in patients with p16-Leiden and multiple primary melanomas. Patients with p16-Leiden had significantly more superficial spreading, and less nodular and lentiginous melanomas. Limitations: Ascertainment of patients with p16-Leiden was family based. The study was performed in families with a founder mutation, the p16-Leiden mutation. Conclusion: Our findings are consistent with a pathogenic pathway of melanoma development from nevi, starting early and ongoing throughout life, and not related to chronic sun exposure. (J Am Acad Dermatol 2011;65:281-8.)Dermatology-oncolog