المؤلفون: Gross, Rachel, Thaweethai, Tanayott, Rosenzweig, Erika, Chan, James, Chibnik, Lori, Cicek, Mine, Elliott, Amy, Flaherman, Valerie, Foulkes, Andrea, Gage Witvliet, Margot, Gallagher, Richard, Gennaro, Maria, Jernigan, Terry, Karlson, Elizabeth, Katz, Stuart, Kinser, Patricia, Kleinman, Lawrence, Lamendola-Essel, Michelle, Milner, Joshua, Mohandas, Sindhu, Mudumbi, Praveen, Newburger, Jane, Rhee, Kay, Salisbury, Amy, Snowden, Jessica, Stein, Cheryl, Stockwell, Melissa, Tantisira, Kelan, Thomason, Moriah, Truong, Dongngan, Warburton, David, Wood, John, Ahmed, Shifa, Akerlundh, Almary, Alshawabkeh, Akram, Anderson, Brett, Aschner, Judy, Atz, Andrew, Aupperle, Robin, Baker, Fiona, Balaraman, Venkataraman, Banerjee, Dithi, Barch, Deanna, Baskin-Sommers, Arielle, Bhuiyan, Sultana, Bind, Marie-Abele, Bogie, Amanda, Bradford, Tamara, Buchbinder, Natalie, Bueler, Elliott, Bükülmez, Hülya, Casey, B, Chang, Linda, Chrisant, Maryanne, Clark, Duncan, Clifton, Rebecca, Clouser, Katharine, Cottrell, Lesley, Cowan, Kelly, DSa, Viren, Dapretto, Mirella, Dasgupta, Soham, Dehority, Walter, Dionne, Audrey, Dummer, Kirsten, Elias, Matthew, Esquenazi-Karonika, Shari, Evans, Danielle, Faustino, E, Fiks, Alexander, Forsha, Daniel, Foxe, John, Friedman, Naomi, Fry, Greta, Gaur, Sunanda, Gee, Dylan, Gray, Kevin, Handler, Stephanie, Harahsheh, Ashraf, Hasbani, Keren, Heath, Andrew, Hebson, Camden, Heitzeg, Mary, Hester, Christina, Hill, Sophia, Hobart-Porter, Laura, Hong, Travis, Horowitz, Carol, Hsia, Daniel, Huentelman, Matthew, Hummel, Kathy, Irby, Katherine, Jacobus, Joanna, Jacoby, Vanessa, Jone, Pei-Ni, Kaelber, David, Kasmarcak, Tyler, Kluko, Matthew, Kosut, Jessica, Laird, Angela

المصدر: PLoS ONE. 19(5)

مصطلحات موضوعية: Humans, COVID-19, Adolescent, Child, Child, Preschool, Female, Young Adult, Adult, Male, Infant, SARS-CoV-2, Infant, Newborn, Prospective Studies, Research Design, Cohort Studies, Post-Acute COVID-19 Syndrome

الوصف: IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or Long COVID) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.govTest. Unique identifier: NCT05172011.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/53x3s0hdTest
https://escholarship.org/content/qt53x3s0hd/qt53x3s0hd.pdfTest

المؤلفون: Gallagher, Richard, Zanetti, Roberto, Rosso, Stefano, Sacchetto, Lidia, Edmiston, Sharon, Conway, Kathleen, Ollila, David, Begg, Colin, Berwick, Marianne, Ward, Sarah, Orlow, Irene, Gibbs, David, Thomas, Nancy, Kanetsky, Peter, Luo, Li, Busam, Klaus, Cust, Anne, Anton-Culver, Hoda

المصدر: JNCI Cancer Spectrum. 7(5)

مصطلحات موضوعية: Humans, Vitamin D-Binding Protein, Vitamin D, Polymorphism, Single Nucleotide, Melanoma

الوصف: BACKGROUND: It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D-binding protein gene (GC), rs7041 and rs4588, determine 3 common haplotypes, Gc1s, Gc1f, and Gc2, of which Gc1f may be associated with decreased all-cause death among melanoma patients based on results of a prior study, but the association of Gc1f with melanoma-specific death is unclear. METHODS: We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4490 individuals with incident, invasive primary melanoma in 2 population-based studies using multivariable Cox-proportional hazards regression. RESULTS: In the pooled analysis of both datasets, the patients with the Gc1f haplotype had a 37% lower risk of melanoma-specific death than the patients without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P = .001), with adjustments for age, sex, study center, first- or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those patients with the Gc1f haplotype compared with those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumor Breslow thickness equal to or less than 2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumor Breslow thickness greater than 2.0 mm (Pinteraction = .003). CONCLUSIONS: Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma-specifically from thicker, higher-risk melanoma-than individuals without this Gc1f haplotype.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0rp246tnTest

المؤلفون: Ward, Sarah V, Autuori, Isidora, Luo, Li, LaPilla, Emily, Yoo, Sarah, Sharma, Ajay, Busam, Klaus J, Olilla, David W, Dwyer, Terence, Anton-Culver, Hoda, Zanetti, Roberto, Sacchetto, Lidia, Cust, Anne E, Gallagher, Richard P, Kanetsky, Peter A, Rosso, Stefano, Begg, Colin B, Berwick, Marianne, Thomas, Nancy E, Orlow, Irene

المصدر: Cancers. 15(10)

مصطلحات موضوعية: Genetics, Cancer, Prevention, MDM2, MDM4, melanoma, gene, polymorphism, risk, survival, sex, functional, estrogen-receptor, GEM Study Group, Oncology and Carcinogenesis

الوصف: MDM2-SNP309 (rs2279744), a common genetic modifier of cancer incidence in Li-Fraumeni syndrome, modifies risk, age of onset, or prognosis in a variety of cancers. Melanoma incidence and outcomes vary by sex, and although SNP309 exerts an effect on the estrogen receptor, no consensus exists on its effect on melanoma. MDM2 and MDM4 restrain p53-mediated tumor suppression, independently or together. We investigated SNP309, an a priori MDM4-rs4245739, and two coinherited variants, in a population-based cohort of 3663 primary incident melanomas. Per-allele and per-haplotype (MDM2_SNP309-SNP285; MDM4_rs4245739-rs1563828) odds ratios (OR) for multiple-melanoma were estimated with logistic regression models. Hazard ratios (HR) for melanoma death were estimated with Cox proportional hazards models. In analyses adjusted for covariates, females carrying MDM4-rs4245739*C were more likely to develop multiple melanomas (ORper-allele = 1.25, 95% CI 1.03-1.51, and Ptrend = 0.03), while MDM2-rs2279744*G was inversely associated with melanoma-death (HRper-allele = 0.63, 95% CI 0.42-0.95, and Ptrend = 0.03). We identified 16 coinherited expression quantitative loci that control the expression of MDM2, MDM4, and other genes in the skin, brain, and lungs. Our results suggest that MDM4/MDM2 variants are associated with the development of subsequent primaries and with the death of melanoma in a sex-dependent manner. Further investigations of the complex MDM2/MDM4 motif, and its contribution to the tumor microenvironment and observed associations, are warranted.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7fc559gbTest

المؤلفون: Davari, Danielle R, Orlow, Irene, Kanetsky, Peter A, Luo, Li, Edmiston, Sharon N, Conway, Kathleen, Parrish, Eloise A, Hao, Honglin, Busam, Klaus J, Sharma, Ajay, Kricker, Anne, Cust, Anne E, Anton-Culver, Hoda, Gruber, Stephen B, Gallagher, Richard P, Zanetti, Roberto, Rosso, Stefano, Sacchetto, Lidia, Dwyer, Terence, Ollila, David W, Begg, Colin B, Berwick, Marianne, Thomas, Nancy E, Group, on behalf of the GEM Study

المصدر: Cancer Epidemiology Biomarkers & Prevention. 30(12)

مصطلحات موضوعية: Clinical Research, Human Genome, Cardiovascular, Cancer, Genetics, Diabetes, Heart Disease, Heart Disease - Coronary Heart Disease, Aged, Cyclin-Dependent Kinase Inhibitor p15, Female, GTP Phosphohydrolases, Genome-Wide Association Study, Humans, Lymphocytes, Tumor-Infiltrating, Male, Melanoma, Membrane Proteins, Middle Aged, Mutation, Proto-Oncogene Proteins B-raf, Skin Neoplasms, coronary artery disease, coronary artery calci fi cation, myocardial, GEM Study Group, Medical and Health Sciences, Epidemiology

الوصف: BackgroundGenome-wide association studies have reported that genetic variation at ANRIL (CDKN2B-AS1) is associated with risk of several chronic diseases including coronary artery disease, coronary artery calcification, myocardial infarction, and type 2 diabetes mellitus. ANRIL is located at the CDKN2A/B locus, which encodes multiple melanoma tumor suppressors. We investigated the association of these variants with melanoma prognostic characteristics.MethodsThe Genes, Environment, and Melanoma Study enrolled 3,285 European origin participants with incident invasive primary melanoma. For each of ten disease-associated SNPs at or near ANRIL, we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and ORs for presence of ulceration and tumor-infiltrating lymphocytes (TIL). We also assessed effect modification by tumor NRAS/BRAF mutational status.ResultsRs518394, rs10965215, and rs564398 passed false discovery and were each associated (P ≤ 0.005) with TILs, although only rs564398 was independently associated (P = 0.0005) with TILs. Stratified by NRAS/BRAF mutational status, rs564398*A was significantly positively associated with TILs among NRAS/BRAF mutant, but not wild-type, cases. We did not find SNP associations with Breslow thickness or ulceration.ConclusionsANRIL rs564398 was associated with TIL presence in primary melanomas, and this association may be limited to NRAS/BRAF-mutant cases.ImpactPathways related to ANRIL variants warrant exploration in relationship to TILs in melanoma, especially given the impact of TILs on immunotherapy and survival.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7ck2z7drTest

المؤلفون: Yardman-Frank, Joseph Michael, Bronner, Baillie, Rosso, Stefano, From, Lynn, Busam, Klaus, Groben, Pam, Tucker, Paul, Cust, Anne, Armstrong, Bruce, Kricker, Anne, Marrett, Loraine, Anton-Culver, Hoda, Gruber, Stephen, Gallagher, Rick, Zanetti, Roberto, Sacchetto, Lidia, Dwyer, Terry, Venn, Alison, Orlow, Irene, Kanetsky, Peter, Luo, Li, Thomas, Nancy, Begg, Colin, Berwick, Marianne, Team, GEM Study, Busam, Klaus J, Autuori, Isidora, Roy, Pampa, Reiner, Anne, Boyce, Tawny W, Cust, Anne E, Armstrong, Bruce K, Dwyer, Terence, Gallagher, Richard P, Marrett, Loraine D, Gruber, Stephen B, Bonner, Joseph D, Thomas, Nancy E, Conway, Kathleen, Ollila, David W, Groben, Pamela A, Edmiston, Sharon N, Hao, Honglin, Parrish, Eloise, Frank, Jill S, Gibbs, David C, Rebbeck, Timothy R, Kanetsky, Peter A, Taylor, Julia Lee, Madronich, Sasha

مصطلحات موضوعية: Data Management and Data Science, Information and Computing Sciences, Biomedical and Clinical Sciences, GEM Study Team

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9tj7k3d7Test

المؤلفون: Yardman-Frank, Joseph Michael, Glassheim, Elyssa, Kricker, Anne, Armstrong, Bruce K, Marrett, Loraine D, Luo, Li, Cust, Anne E, Busam, Klaus J, Orlow, Irene, Gallagher, Richard P, Gruber, Stephen B, Anton-Culver, Hoda, Rosso, Stefano, Zanetti, Roberto, Sacchetto, Lidia, Kanetsky, Peter A, Dwyer, Terence, Venn, Alison, Lee-Taylor, Julia, Begg, Colin B, Thomas, Nancy E, Berwick, Marianne

المصدر: JID Innovations. 1(1)

مصطلحات موضوعية: Climate Change Impacts and Adaptation, Biomedical and Clinical Sciences, Environmental Sciences, Health Sciences, Cancer

الوصف: In an effort to understand the difference between melanomas diagnosed in Australia (New South Wales) and Canada, where the incidence in New South Wales is almost three times greater than in Canada, and mortality is twice as high although survival is slightly more favorable, we had one pathologist review 1,271 melanomas from British Columbia and Ontario, Canada, to compare these to melanomas in New South Wales, Australia. We hypothesized that histopathologic characteristics might provide insight into divergent pathways to melanoma development. We found a number of differences in risk factors and tumor characteristics between the two geographic areas. There were higher mole counts and darker phenotypes in the Canadian patients, while the Australian patients had greater solar elastosis, more lentigo maligna melanomas, and more tumor infiltrating lymphocytes. We hypothesize that the differences observed may illustrate different etiologies – the cumulative exposure pathway among Australian patients and the nevus pathway among Canadian patients. This is one of the largest studies investigating the divergent pathway hypothesis and is particularly robust due to the evaluation of all lesions by one dermatopathologist.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1500t80pTest

المؤلفون: Davari, Danielle R, Orlow, Irene, Kanetsky, Peter A, Luo, Li, Busam, Klaus J, Sharma, Ajay, Kricker, Anne, Cust, Anne E, Anton-Culver, Hoda, Gruber, Stephen B, Gallagher, Richard P, Zanetti, Roberto, Rosso, Stefano, Sacchetto, Lidia, Dwyer, Terence, Gibbs, David C, Ollila, David W, Begg, Colin B, Berwick, Marianne, Thomas, Nancy E

المصدر: Current Oncology. 28(6)

مصطلحات موضوعية: Genetics, Clinical Research, Human Genome, Cancer, Aetiology, 2.1 Biological and endogenous factors, Genome-Wide Association Study, Humans, Lymphocytes, Tumor-Infiltrating, Melanoma, Prognosis, Skin Neoplasms, melanoma, single nucleotide polymorphism, Breslow thickness, ulceration, mitoses, tumor-infiltrating lymphocytes, survival, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: Genome-wide association studies (GWAS) and candidate pathway studies have identified low-penetrant genetic variants associated with cutaneous melanoma. We investigated the association of melanoma-risk variants with primary melanoma tumor prognostic characteristics and melanoma-specific survival. The Genes, Environment, and Melanoma Study enrolled 3285 European origin participants with incident invasive primary melanoma. For each of 47 melanoma-risk single nucleotide polymorphisms (SNPs), we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and odds ratios for presence of ulceration, mitoses, and tumor-infiltrating lymphocytes (TILs). We also used Cox proportional hazards regression modeling to estimate the per allele hazard ratios for melanoma-specific survival. Passing the false discovery threshold (p = 0.0026) were associations of IRF4 rs12203592 and CCND1 rs1485993 with log of Breslow thickness, and association of TERT rs2242652 with presence of mitoses. IRF4 rs12203592 also had nominal associations (p < 0.05) with presence of mitoses and melanoma-specific survival, as well as a borderline association (p = 0.07) with ulceration. CCND1 rs1485993 also had a borderline association with presence of mitoses (p = 0.06). MX2 rs45430 had nominal associations with log of Breslow thickness, presence of mitoses, and melanoma-specific survival. Our study indicates that further research investigating the associations of these genetic variants with underlying biologic pathways related to tumor progression is warranted.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6d63x48kTest

المؤلفون: Wood, Renee P, Heyworth, Jane S, McCarthy, Nina S, Mauguen, Audrey, Berwick, Marianne, Thomas, Nancy E, Millward, Michael J, Anton-Culver, Hoda, Cust, Anne E, Dwyer, Terence, Gallagher, Richard P, Gruber, Stephen B, Kanetsky, Peter A, Orlow, Irene, Rosso, Stefano, Moses, Eric K, Begg, Colin B, Ward, Sarah V

المصدر: Cancer Epidemiology Biomarkers & Prevention. 29(11)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Dental/Oral and Craniofacial Disease, Clinical Trials and Supportive Activities, Cancer, Clinical Research, Aged, Female, Humans, Male, Melanoma, Middle Aged, Neck, Risk Factors, Scalp, Skin Neoplasms, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences

الوصف: BackgroundScalp and neck (SN) melanoma confers a worse prognosis than melanoma of other sites but little is known about its determinants. We aimed to identify associations between SN melanoma and known risk genes, phenotypic traits, and sun exposure patterns.MethodsParticipants were cases from the Western Australian Melanoma Health Study (n = 1,200) and the Genes, Environment, and Melanoma Study (n = 3,280). Associations between risk factors and SN melanoma, compared with truncal and arm/leg melanoma, were investigated using binomial logistic regression. Facial melanoma was also compared with the trunk and extremities, to evaluate whether associations were subregion specific, or reflective of the whole head/neck region.ResultsCompared with other sites, increased odds of SN and facial melanoma were observed in older individuals [SN: OR = 1.28, 95% confidence interval (CI) = 0.92-1.80, P trend = 0.016; Face: OR = 4.57, 95% CI = 3.34-6.35, P trend < 0.001] and those carrying IRF4-rs12203592*T (SN: OR = 1.35, 95% CI = 1.12-1.63, P trend = 0.002; Face: OR = 1.29, 95% CI = 1.10-1.50, P trend = 0.001). Decreased odds were observed for females (SN: OR = 0.49, 95% CI = 0.37-0.64, P < 0.001; Face: OR = 0.66, 95% CI = 0.53-0.82, P < 0.001) and the presence of nevi (SN: OR = 0.66, 95% CI = 0.49-0.89, P = 0.006; Face: OR = 0.65, 95% CI = 0.52-0.83, P < 0.001).ConclusionsDifferences observed between SN melanoma and other sites were also observed for facial melanoma. Factors previously associated with the broader head and neck region, notably older age, may be driven by the facial subregion. A novel finding was the association of IRF4-rs12203592 with both SN and facial melanoma.ImpactUnderstanding the epidemiology of site-specific melanoma will enable tailored strategies for risk factor reduction and site-specific screening campaigns.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/97s4q6fvTest

المؤلفون: Di Bartolo, Christina A., Abikoff, Howard, McDonald, Margaret, Gallagher, Richard

المصدر: Psychology in the Schools. Jul 2021 58(7):1225-1245.

تمت مراجعته من قبل الزملاء: Y

Page Count: 21

الواصفات: Time Management, Planning, Skill Development, Training, Elementary School Students, Small Group Instruction, Intervention, Assignments, Homework, Outcomes of Education, Executive Function

مستخلص: Effective organizational skills (e.g., time management, materials management, and task planning) are associated with academic success, yet some children struggle to gain these skills without intervention. While evidence-based organizational skills interventions for pediatric clinical populations exist, none target organizationally impaired general populations in a primary school setting. In Organizational Skills Training-School (OST-S), school professionals teach small groups of 4th-5th grade organizationally impaired elementary school students skills associated with tracking assignments, managing materials, time management, and planning. This open pilot study of 33 students examined: a. the feasibility of adapting and implementing an established clinic-based, individualized treatment (OST-C) to a group format in a school setting, b. the program's acceptability among children, parents, and school partners, and c. whether participating children improved in the same functional areas that OST-C positively influenced. Results indicated that we could adapt the intervention, school partners could implement it, and participants could accept it. Pre-post improvements in organizational skills (as rated by parents, teachers, and children), homework problems, and academic performance demonstrated the potential effectiveness of OST-S, suggesting the need for further efficacy work.

Abstractor: As Provided

المؤلفون: Pellegrini, Cristina, Botta, Francesca, Massi, Daniela, Martorelli, Claudia, Facchetti, Fabio, Gandini, Sara, Maisonneuve, Patrick, Avril, Marie-Françoise, Demenais, Florence, Paillerets, Brigitte Bressac-de, Hoiom, Veronica, Cust, Anne E, Anton-Culver, Hoda, Gruber, Stephen B, Gallagher, Richard P, Marrett, Loraine, Zanetti, Roberto, Dwyer, Terence, Thomas, Nancy E, Begg, Colin B, Berwick, Marianne, Puig, Susana, Potrony, Miriam, Nagore, Eduardo, Ghiorzo, Paola, Menin, Chiara, Manganoni, Ausilia Maria, Rodolfo, Monica, Brugnara, Sonia, Passoni, Emanuela, Sekulovic, Lidija Kandolf, Baldini, Federica, Guida, Gabriella, Stratigos, Alexandros, Ozdemir, Fezal, Ayala, Fabrizio, Fernandez-de-Misa, Ricardo, Quaglino, Pietro, Ribas, Gloria, Romanini, Antonella, Migliano, Emilia, Stanganelli, Ignazio, Kanetsky, Peter A, Pizzichetta, Maria Antonietta, García-Borrón, Jose Carlos, Nan, Hongmei, Landi, Maria Teresa, Little, Julian, Newton-Bishop, Julia, Sera, Francesco, Fargnoli, Maria Concetta, Raimondi, Sara, Group, IMI Study, Alaibac, Mauro, Ferrari, Andrea, Valeri, Barbara, Sicher, Mariacristina, Mangiola, Daniela, Nazzaro, Gianluca, Tosti, Giulio, Mazzarol, Giovanni, Giudice, Giuseppe, Ribero, Simone, Astrua, Chiara, Mazzoni, Laura, Group, GEM Study, Orlow, Irene, Mujumdar, Urvi, Hummer, Amanda, Busam, Klaus, Roy, Pampa, Canchola, Rebecca, Clas, Brian, Cotignola, Javiar, Monroe, Yvette, Armstrong, Bruce, Kricker, Anne, Litchfield, Melisa, Tucker, Paul, Stephens, Nicola, Switzer, Teresa, Theis, Beth, From, Lynn, Chowdhury, Noori, Vanasse, Louise, Purdue, Mark, Northrup, David, Rosso, Stefano, Sacerdote, Carlotta, Leighton, Nancy, Gildea, Maureen, Bonner, Joe, Jeter, Joanne, Klotz, Judith, Wilcox, Homer, Weiss, Helen, Millikan, Robert, Mattingly, Dianne, Player, Jon

المصدر: The Lancet Child & Adolescent Health. 3(5)

مصطلحات موضوعية: Clinical Research, Pediatric, Genetics, Prevention, Cancer, Adolescent, Adult, Aged, Biomarkers, Tumor, Case-Control Studies, Child, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Logistic Models, Male, Melanoma, Middle Aged, Odds Ratio, Polymorphism, Genetic, Receptor, Melanocortin, Type 1, Retrospective Studies, Skin Neoplasms, IMI Study Group, GEM Study Group, M-SKIP Study Group

الوصف: BackgroundGermline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls.MethodsIn this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger.FindingsWe analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants.InterpretationOur pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies.FundingSPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4144d96wTest