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1. Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth.

Author

Ghantous, Akram, Nusslé, Semira, Nassar, Farah, Spitz, Natalia, Novoloaca, Alexei, Krali, Olga, Nickels, Eric, Cahais, Vincent, Cuenin, Cyrille, Roy, Ritu, Li, Shaobo, Caron, Maxime, Lam, Dilys, Fransquet, Peter, Casement, John, Strathdee, Gordon, Pearce, Mark, Hansen, Helen, Lee, Hwi-Ho, Lee, Yong, de Smith, Adam, Sinnett, Daniel, Håberg, Siri, McKay, Jill, Nordlund, Jessica, Magnus, Per, Dwyer, Terence, Saffery, Richard, Wiemels, Joseph, Munthe-Kaas, Monica, and Herceg, Zdenko

Subjects
VTRNA2-1, Birth cohort, DNA methylation, Epigenetics, Neonatal blood spots, Pediatric leukemia, Humans, DNA Methylation, Female, Male, Epigenome, Child, Epigenesis, Genetic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Child, Preschool, Infant, Newborn, Infant, Biomarkers, Tumor, Prognosis, Case-Control Studies, Adolescent
Abstract

BACKGROUND: Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation. METHODS: Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations. RESULTS: The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR

Published
2024

3. A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Author

Li, Shaobo, Spitz, Natalia, Ghantous, Akram, Abrishamcar, Sarina, Reimann, Brigitte, Marques, Irene, Silver, Matt J, Aguilar-Lacasaña, Sofía, Kitaba, Negusse, Rezwan, Faisal I, Röder, Stefan, Sirignano, Lea, Tuhkanen, Johanna, Mancano, Giulia, Sharp, Gemma C, Metayer, Catherine, Morimoto, Libby, Stein, Dan J, Zar, Heather J, Alfano, Rossella, Nawrot, Tim, Wang, Congrong, Kajantie, Eero, Keikkala, Elina, Mustaniemi, Sanna, Ronkainen, Justiina, Sebert, Sylvain, Silva, Wnurinham, Vääräsmäki, Marja, Jaddoe, Vincent WV, Bernstein, Robin M, Prentice, Andrew M, Cosin-Tomas, Marta, Dwyer, Terence, Håberg, Siri Eldevik, Herceg, Zdenko, Magnus, Maria C, Munthe-Kaas, Monica Cheng, Page, Christian M, Völker, Maja, Gilles, Maria, Send, Tabea, Witt, Stephanie, Zillich, Lea, Gagliardi, Luigi, Richiardi, Lorenzo, Czamara, Darina, Räikkönen, Katri, Chatzi, Lida, Vafeiadi, Marina, Arshad, S Hasan, Ewart, Susan, Plusquin, Michelle, Felix, Janine F, Moore, Sophie E, Vrijheid, Martine, Holloway, John W, Karmaus, Wilfried, Herberth, Gunda, Zenclussen, Ana, Streit, Fabian, Lahti, Jari, Hüls, Anke, Hoang, Thanh T, London, Stephanie J, and Wiemels, Joseph L

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Genetics, Biological Sciences, Human Genome, Contraception/Reproduction, Pediatric, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Good Health and Well Being, Child, Female, Humans, Infant, Newborn, Pregnancy, Birth Order, DNA Methylation, Epigenesis, Genetic, Epigenomics, Biological sciences, Biomedical and clinical sciences
Abstract

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P

Published
2024

4. Sex-Specific Associations of MDM2 and MDM4 Variants with Risk of Multiple Primary Melanomas and Melanoma Survival in Non-Hispanic Whites

Author

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, and Orlow, Irene

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

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.

Published
2023

6. Common maternal infections during pregnancy and childhood leukaemia in the offspring: findings from six international birth cohorts.

Author

He, Jian-Rong, Hirst, Jane E, Tikellis, Gabriella, Phillips, Gary S, Ramakrishnan, Rema, Paltiel, Ora, Ponsonby, Anne-Louise, Klebanoff, Mark, Olsen, Jørn, Murphy, Michael FG, Håberg, Siri E, Lemeshow, Stanley, F Olsen, Sjurdur, Qiu, Xiu, Magnus, Per, Golding, Jean, Ward, Mary H, Wiemels, Joseph L, Rahimi, Kazem, Linet, Martha S, and Dwyer, Terence

Subjects
Cancer, Pediatric Cancer, Infectious Diseases, Childhood Leukemia, Prevention, Hematology, Rare Diseases, Pediatric, Pediatric Research Initiative, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Acute Disease, Birth Cohort, Child, Female, Humans, Influenza, Human, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Pregnancy, Prospective Studies, Risk Factors, International Childhood Cancer Cohort Consortium, Maternal infection, childhood leukaemia, cohort study, prenatal, Statistics, Public Health and Health Services, Epidemiology
Abstract

BackgroundPrevious epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data.MethodsData were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models.ResultsAmong 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10-2.58)] and subtypes ALL [1.49 (0.87-2.56)] and AML [2.70 ([0.93-7.86)], but not with any cancer [1.13 (0.85-1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06-2.34)], ALL [1.43 (0.94-2.19)], AML [2.37 (1.10-5.12)] and any cancer [1.33 (1.09-1.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes.ConclusionsUrinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.

Published
2022

7. Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

Author

Solomon, Olivia, Huen, Karen, Yousefi, Paul, Küpers, Leanne K, González, Juan R, Suderman, Matthew, Reese, Sarah E, Page, Christian M, Gruzieva, Olena, Rzehak, Peter, Gao, Lu, Bakulski, Kelly M, Novoloaca, Alexei, Allard, Catherine, Pappa, Irene, Llambrich, Maria, Vives, Marta, Jima, Dereje D, Kvist, Tuomas, Baccarelli, Andrea, White, Cory, Rezwan, Faisal I, Sharp, Gemma C, Tindula, Gwen, Bergström, Anna, Grote, Veit, Dou, John F, Isaevska, Elena, Magnus, Maria C, Corpeleijn, Eva, Perron, Patrice, Jaddoe, Vincent WV, Nohr, Ellen A, Maitre, Lea, Foraster, Maria, Hoyo, Cathrine, Håberg, Siri E, Lahti, Jari, DeMeo, Dawn L, Zhang, Hongmei, Karmaus, Wilfried, Kull, Inger, Koletzko, Berthold, Feinberg, Jason I, Gagliardi, Luigi, Bouchard, Luigi, Ramlau-Hansen, Cecilia Høst, Tiemeier, Henning, Santorelli, Gillian, Maguire, Rachel L, Czamara, Darina, Litonjua, Augusto A, Langhendries, Jean-Paul, Plusquin, Michelle, Lepeule, Johanna, Binder, Elisabeth B, Verduci, Elvira, Dwyer, Terence, Carracedo, Ángel, Ferre, Natalia, Eskenazi, Brenda, Kogevinas, Manolis, Nawrot, Tim S, Munthe-Kaas, Monica C, Herceg, Zdenko, Relton, Caroline, Melén, Erik, Gruszfeld, Dariusz, Breton, Carrie, Fallin, MD, Ghantous, Akram, Nystad, Wenche, Heude, Barbara, Snieder, Harold, Hivert, Marie-France, Felix, Janine F, Sørensen, Thorkild IA, Bustamante, Mariona, Murphy, Susan K, Raikkönen, Katri, Oken, Emily, Holloway, John W, Arshad, Syed Hasan, London, Stephanie J, and Holland, Nina

Subjects
Humans, DNA Methylation, Epigenesis, Genetic, Pregnancy, Sex Characteristics, Adolescent, Child, Infant, Newborn, Female, Male, Epigenomics, Epigenome, Children, Cord blood, DNA methylation, EWAS, Sex, Digestive Diseases, Human Genome, Genetics, Prevention, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Toxicology
Abstract

BackgroundAmong children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.MethodsWe performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5-10 years from 8 cohorts (n = 4268).ResultsIn newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p

Published
2022

8. Disease-Associated Risk Variants in ANRIL Are Associated with Tumor-Infiltrating Lymphocyte Presence in Primary Melanomas in the Population-Based GEM Study

Author

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, and Group, on behalf of the GEM Study

Subjects
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
Abstract

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.

Published
2021

9. Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Author

Phelps, Nowell H, Singleton, Rosie K, Zhou, Bin, Heap, Rachel A, Mishra, Anu, Bennett, James E, Paciorek, Christopher J, Lhoste, Victor PF, Carrillo-Larco, Rodrigo M, Stevens, Gretchen A, Rodriguez-Martinez, Andrea, Bixby, Honor, Bentham, James, Di Cesare, Mariachiara, Danaei, Goodarz, Rayner, Archie W, Barradas-Pires, Ana, Cowan, Melanie J, Savin, Stefan, Riley, Leanne M, Aguilar-Salinas, Carlos A, Baker, Jennifer L, Barkat, Amina, Bhutta, Zulfiqar A, Branca, Francesco, Caixeta, Roberta B, Cuschieri, Sarah, Farzadfar, Farshad, Ganapathy, Shubash, Ikeda, Nayu, Iotova, Violeta, Kengne, Andre P, Khang, Young-Ho, Laxmaiah, Avula, Lin, Hsien-Ho, Ma, Jun, Mbanya, Jean Claude N, Miranda, J Jaime, Pradeepa, Rajendra, Rodríguez-Artalejo, Fernando, Sorić, Maroje, Turley, Maria, Wang, Limin, Webster-Kerr, Karen, Aarestrup, Julie, Abarca-Gómez, Leandra, Abbasi-Kangevari, Mohsen, Abdeen, Ziad A, Abdrakhmanova, Shynar, Abdul Ghaffar, Suhaila, Abdul Rahim, Hanan F, Abdurrahmonova, Zulfiya, Abu-Rmeileh, Niveen M, Abubakar Garba, Jamila, Acosta-Cazares, Benjamin, Adam, Ishag, Adamczyk, Marzena, Adams, Robert J, Adu-Afarwuah, Seth, Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agbor, Valirie N, Agdeppa, Imelda A, Aghazadeh-Attari, Javad, Ågren, Åsa, Aguenaou, Hassan, Agyemang, Charles, Ahmad, Mohamad Hasnan, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmadi, Nastaran, Ahmed, Imran, Ahmed, Soheir H, Ahrens, Wolfgang, Aitmurzaeva, Gulmira, Ajlouni, Kamel, Al-Hazzaa, Hazzaa M, Al-Hinai, Halima, Al-Lahou, Badreya, Al-Lawati, Jawad A, Al-Raddadi, Rajaa, Al Asfoor, Deena, Al Hourani, Huda M, Al Qaoud, Nawal M, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Aldwairji, Maryam A, Alexius, Sylvia, Ali, Mohamed M, Alieva, Anna V, Alkandari, Abdullah, Alkerwi, Ala'a, Alkhatib, Buthaina M, Allin, Kristine, Alomary, Shaker A, Alomirah, Husam F, Alshangiti, Arwa M, Alvarez-Pedrerol, Mar, Aly, Eman, Amarapurkar, Deepak N, Amiano Etxezarreta, Pilar, Amoah, John, Amougou, Norbert, Amouyel, Philippe, Andersen, Lars Bo, Anderssen, Sigmund A, Androutsos, Odysseas, Ängquist, Lars, Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Anufrieva, Elena, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E, Arlappa, Nimmathota, Aryal, Krishna K, Assefa, Nega, Aspelund, Thor, Assah, Felix K, Assembekov, Batyrbek, Assunção, Maria Cecília F, Aung, May Soe, Aurélio de Valois, Correia Júnior Marco, Auvinen, Juha, Avdičová, Mária, Avi, Shina, Azad, Kishwar, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Babu, Bontha V, Bacopoulou, Flora, Bæksgaard Jørgensen, Maja, Baharudin, Azli, Bahijri, Suhad, Bajramovic, Izet, Bakacs, Marta, Balakrishna, Nagalla, Balanova, Yulia, Bamoshmoosh, Mohamed, Banach, Maciej, Banegas, José R, Baran, Joanna, Baran, Rafał, Barbagallo, Carlo M, Barbosa Filho, Valter, Barceló, Alberto, Baretić, Maja, Barnoya, Joaquin, Barrera, Lena, Barreto, Marta, Barros, Aluisio JD, Barros, Mauro Virgílio Gomes, Bartosiewicz, Anna, Basit, Abdul, Bastos, Joao Luiz, Bata, Iqbal, Batieha, Anwar M, Batista, Aline P, Batista, Rosangela L, Battakova, Zhamilya, Baur, Louise A, Bayauli, Pascal M, Beaglehole, Robert, Bel-Serrat, Silvia, Belavendra, Antonisamy, Ben Romdhane, Habiba, Benedek, Theodora, Benedics, Judith, Benet, Mikhail, Benitez Rolandi, Gilda Estela, Benzeval, Michaela, Bere, Elling, Berger, Nicolas, Bergh, Ingunn Holden, Berhane, Yemane, Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Berrios Carrasola, Ximena, Bettiol, Heloísa, Beutel, Manfred E, Beybey, Augustin F, Bezerra, Jorge, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bi, Hongsheng, Bi, Yufang, Bia, Daniel, Biasch, Katia, Bika Lele, Elysée Claude, Bikbov, Mukharram M, Bista, Bihungum, Bjelica, Dusko J, Bjerregaard, Anne A, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Björkelund, Cecilia, Bloch, Katia V, Blokstra, Anneke, Blychfeld Magnazu, Moran, Bo, Simona, Bobak, Martin, Boddy, Lynne M, Boehm, Bernhard O, Boer, Jolanda MA, Boggia, Jose G, Bogova, Elena, Boissonnet, Carlos P, Bojesen, Stig E, Bonaccio, Marialaura, Bongard, Vanina, Bonilla-Vargas, Alice, Bopp, Matthias, Borghs, Herman, Botomba, Steve, Bourne, Rupert RA, Bovet, Pascal, Boymatova, Khadichamo, Braeckevelt, Lien, Braeckman, Lutgart, Bragt, Marjolijn CE, Braithwaite, Tasanee, Brajkovich, Imperia, Breckenkamp, Juergen, Breda, João, Brenner, Hermann, Brewster, Lizzy M, Brian, Garry R, Briceño, Yajaira, Brinduse, Lacramioara, Bringolf-Isler, Bettina, Brito, Miguel, Brophy, Sinead, Brug, Johannes, Bruno, Graziella, Bugge, Anna, Buoncristiano, Marta, Burazeri, Genc, Burns, Con, Cabrera de León, Antonio, Cacciottolo, Joseph, Cai, Hui, Cama, Tilema, Cameron, Christine, Camolas, José, Can, Günay, Cândido, Ana Paula c, Cañete, Felicia, Capanzana, Mario V, Čapková, Naděžda, Capuano, Eduardo, Capuano, Rocco, Capuano, Vincenzo, Cardol, Marloes, Cardoso, Viviane C, Carlsson, Axel C, Carmuega, Esteban, Carvalho, Joana, Casajús, José A, Casanueva, Felipe F, Casas, Maribel, Celikcan, Ertugrul, Censi, Laura, Cervantes-Loaiza, Marvin, Cesar, Juraci A, Chamnan, Parinya, Chamukuttan, Snehalatha, Chan, Angelique, Chan, Queenie, Charchar, Fadi J, Charles, Marie-Aline, Chaturvedi, Himanshu K, Chaturvedi, Nish, Che Abdul Rahim, Norsyamlina, Chee, Miao Li, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Long-Sheng, Chen, Shuohua, Chen, Zhengming, Cheng, Ching-Yu, Cheng, Yiling J, Cheraghian, Bahman, Chetrit, Angela, Chikova-Iscener, Ekaterina, Chinapaw, Mai JM, Chinnock, Anne, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolores, Cho, Belong, Christensen, Kaare, Christofaro, Diego G, Chudek, Jerzy, Cifkova, Renata, Cilia, Michelle, Cinteza, Eliza, Cirillo, Massimo, Claessens, Frank, Clare, Philip, Clarke, Janine, Clays, Els, Cohen, Emmanuel, Cojocaru, Cosmin R, Colorado-Yohar, Sandra, Compañ-Gabucio, Laura-María, Concin, Hans, Confortin, Susana C, Cooper, Cyrus, Coppinger, Tara C, Corpeleijn, Eva, Cortés, Lilia Yadira, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L, Crampin, Amelia C, Cross, Amanda J, Crujeiras, Ana B, Cruz, Juan J, Csányi, Tamás, Csilla, Semánová, Cucu, Alexandra M, Cui, Liufu, Cureau, Felipe V, Czenczek-Lewandowska, Ewelina, D'Arrigo, Graziella, d'Orsi, Eleonora, da Silva, Alanna G, Dacica, Liliana, Dahm, Christina C, Dallongeville, Jean, Damasceno, Albertino, Damsgaard, Camilla T, Dankner, Rachel, Dantoft, Thomas M, Dasgupta, Parasmani, Dastgiri, Saeed, Dauchet, Luc, Davletov, Kairat, de Assis Guedes de Vasconcelos, Francisco, de Assis, Maria Alice Altenburg, De Backer, Guy, De Bacquer, Dirk, De Bacquer, Jaco, de Bont, Jeroen, De Curtis, Amalia, de Fragas Hinnig, Patrícia, de Gaetano, Giovanni, De Henauw, Stefaan, De Miguel-Etayo, Pilar, De Neve, Jan-Walter, Duarte de Oliveira, Paula, De Ridder, David, De Ridder, Karin, de Rooij, Susanne R, de Sá, Ana Carolina MGN, De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D, DeGennaro, Vincent Jr, Delisle, Hélène, Delpeuch, Francis, Demarest, Stefaan, Dennison, Elaine, Dereń, Katarzyna, Deschamps, Valérie, Devrishov, Ruslan D, Dhimal, Meghnath, Di Castelnuovo, Augusto, Dias-da-Costa, Juvenal Soares, Díaz-Sánchez, María Elena, Diaz, Alejandro, Díaz Fernández, Pedro, Díez Ripollés, María Pilar, Dika, Zivka, Djalalinia, Shirin, Djordjic, Visnja, Do, Ha TP, Dobson, Annette J, Dominguez, Liria, Donati, Maria Benedetta, Donfrancesco, Chiara, Dong, Guanghui, Dong, Yanhui, Donoso, Silvana P, Döring, Angela, Dorobantu, Maria, Dorosty, Ahmad Reza, Dörr, Marcus, Doua, Kouamelan, Dragano, Nico, Drygas, Wojciech, Du, Shufa, Duan, Jia Li, Duante, Charmaine A, Duboz, Priscilla, Duleva, Vesselka L, Dulskiene, Virginija, Dumith, Samuel C, Dushpanova, Anar, Dwyer, Terence, Dyussupova, Azhar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Ebrahimi, Narges, Echeverría, Guadalupe, Eddie, Ricky, Eftekhar, Ebrahim, Efthymiou, Vasiliki, Egbagbe, Eruke E, Eggertsen, Robert, Eghtesad, Sareh, Eiben, Gabriele, Ekelund, Ulf, El-Khateeb, Mohammad, El Ammari, Laila, El Ati, Jalila, Eldemire-Shearer, Denise, Elliott, Paul, Enang, Ofem, Endevelt, Ronit, Engle-Stone, Reina, Erasmus, Rajiv T, Erem, Cihangir, Ergor, Gul, Eriksen, Louise, Eriksson, Johan G, Escobedo-de la Peña, Jorge, Eslami, Saeid, Esmaeili, Ali, Evans, Alun, Evans, Roger G, Faeh, David, Fagherazzi, Guy, Fakhradiyev, Ildar, Fakhretdinova, Albina A, Fall, Caroline H, Faramarzi, Elnaz, Farjam, Mojtaba, Farrugia Sant'Angelo, Victoria, Farzi, Yosef, Fattahi, Mohammad Reza, Fawwad, Asher, Fawzi, Wafaie W, Felix-Redondo, Francisco J, Ferguson, Trevor S, Fernandes, Romulo A, Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrao, Thomas, Ferrari, Gerson, Ferrari, Marika, Ferrario, Marco M, Ferreccio, Catterina, Ferreira, Haroldo S, Ferrer, Eldridge, Ferrieres, Jean, Figueiró, Thamara Hubler, Fijalkowska, Anna, Fink, Günther, Fisberg, Mauro, Fischer, Krista, Foo, Leng Huat, Forsner, Maria, 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Alireza, Safarpour, Ali Reza, Safi, Sare, Safiri, Saeid, Saghi, Mohammad Hossien, Saidi, Olfa, Saieva, Calogero, Sakata, Satoko, Saki, Nader, Šalaj, Sanja, Salanave, Benoit, Salazar Martinez, Eduardo, Salhanova, Akkumis, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sánchez Rodríguez, Inés, Sandjaja, Sans, Susana, Santa-Marina, Loreto, Santacruz, Ethel, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Santos, Tamara R, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savvas, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Schaffrath Rosario, Angelika, Schargrodsky, Herman, Schienkiewitz, Anja, Schindler, Karin, Schipf, Sabine, Schmidt, Börge, Schmidt, Carsten O, Schmidt, Ida Maria, Schneider, Andrea, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schultz, Gry, Schulze, Matthias B, Schutte, Aletta E, Sebert, Sylvain, Sedaghattalab, Moslem, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Guillermo, Serra-Majem, Luis, Servais, Jennifer, Ševčíková, Ľudmila, Sewpaul, Ronel, Shalnova, Svetlana, Shamah-Levy, Teresa, Shamshirgaran, Seyed Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Sharman, Almaz, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shimony, Tal, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Sidossis, Labros S, Silitrari, Natalia, Silva, Antonio M, Silva, Caroline Ramos de Moura, Silva, Diego Augusto Santos, Silva, Kelly Samara, Sim, Xueling, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skoblina, Elena V, Skoblina, Natalia A, Slazhnyova, Tatyana, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemysław, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinus, Sofat, Reecha, Solfrizzi, Vincenzo, Solovieva, Yuliya V, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Soofi, Sajid, Sørensen, Thorkild IA, Sørgjerd, Elin P, Sossa Jérome, Charles, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sousa-Poza, Alfonso, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spencer, Phoebe R, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stang, Andreas, Starc, Gregor, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Steinsbekk, Silje, Stergiou, George S, Stessman, Jochanan, Stevanović, Ranko, Stieber, Jutta, Stöckl, Doris, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suarez-Ortegón, Milton F, Suebsamran, Phalakorn, Sugiyama, Mindy, Suka, Machi, Sulo, Gerhard, Sun, Chien-An, Sun, Liang, Sund, Malin, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Sweis, Nabil William G, Swinburn, Boyd A, Sy, Rody G, Sylva, René Charles, Szponar, Lucjan, Tabone, Lorraine, Tai, E Shyong, Takuro, Furusawa, Tambalis, Konstantinos D, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Taxová Braunerová, Radka, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Te Velde, Saskia, Tebar, William R, Tell, Grethe S, Tello, Tania, Tessema, Masresha, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thomas, Nihal, Thorand, Barbara, Thrift, Amanda G, Tichá, Ľubica, Timmermans, Erik J, Tjandrarini, Dwi Hapsari, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Tomaszewski, Maciej, Topbas, Murat, Topór-Mądry, Roman, Torheim, Liv Elin, Tornaritis, Michael J, Torrent, Maties, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Tremblay, Mark S, Triantafyllou, Areti, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsintavis, Panagiotis, Tsugane, Shoichiro, Tuitele, John, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Twig, Gilad, Tynelius, Per, Tzala, Evangelia, Tzotzas, Themistoklis, Tzourio, Christophe, Udoji, Nwannedimma, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, van den Born, Bert-Jan, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Lippevelde, Wendy, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Vargas, Luz Nayibe, Varona-Pérez, Patricia, Vasan, Senthil K, Vasques, Daniel G, Vatasescu, Radu, Vega, Tomas, Veidebaum, Toomas, Velasquez-Melendez, Gustavo, Velika, Biruta, Verloigne, Maïté, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Vik, Frøydis N, Vilar, Monica, Villalpando, Salvador, Vioque, Jesus, Viriyautsahakul, Napaphan, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Vourli, Georgia, Voutilainen, Ari, Vrijheid, Martine, Vrijkotte, Tanja GM, Vuletić, Silvije, Wade, Alisha N, Waldhör, Thomas, Walton, Janette, Wambiya, Elvis OA, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley Júnior, Rildo de Souza, Wang, Chongjian, Wang, Huijun, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nicholas, Wartha, Olivia, Weber, Adelheid, Wedderkopp, Niels, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Westbury, Leo D, Whincup, Peter H, Wichstrøm, Lars, Wickramasinghe, Kremlin, Widhalm, Kurt, Widyahening, Indah S, Więcek, Andrzej, Wild, Philipp S, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wirth, James P, Wojtyniak, Bogdan, Woldeyohannes, Meseret, Wolf, Kathrin, Wong-McClure, Roy A, Wong, Andrew, Wong, Emily B, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Hon-Yen, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Wyszyńska, Justyna, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Li, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yasuharu, Tabara, Yépez García, Martha, Yiallouros, Panayiotis K, Yngve, Agneta, Yoosefi, Moein, Yoshihara, Akihiro, Yotov, Yoto, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Yu, Yu-Ling, Yu, Yunjiang, Yusof, Safiah Md, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassilis, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antonis, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Zaw, Ko Ko, Zayed, Ayman A, Zdrojewski, Tomasz, Żegleń, Magdalena, Zejglicova, Kristyna, Zeljkovic Vrkic, Tajana, Zeng, Yi, Zentai, Andrea, Zhang, Bing, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhecheva, Yanitsa V, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zimmet, Paul, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Zoghlami, Nada, Zuñiga Cisneros, Julio, Zuziak, Monika, and Ezzati, Majid

Published
2024
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13. Comparison of community pathologists with expert dermatopathologists evaluating Breslow thickness and histopathologic subtype in a large international population-based study of melanoma

Author

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, and Madronich, Sasha

Subjects
Data Management and Data Science, Information and Computing Sciences, Biomedical and Clinical Sciences, GEM Study Team
Published
2021

16. Differences in Melanoma Between Canada and New South Wales, Australia: A Population-Based Genes, Environment, and Melanoma (GEM) Study

Author

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, and Berwick, Marianne

Subjects
Climate Change Impacts and Adaptation, Biomedical and Clinical Sciences, Environmental Sciences, Health Sciences, Cancer
Abstract

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.

Published
2021

17. Association of Melanoma-Risk Variants with Primary Melanoma Tumor Prognostic Characteristics and Melanoma-Specific Survival in the GEM Study

Author

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, and Thomas, Nancy E

Subjects
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
Abstract

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.

Published
2021

18. Association of Known Melanoma Risk Factors with Primary Melanoma of the Scalp and Neck

Author

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, and Ward, Sarah V

Subjects
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
Abstract

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.

Published
2020

19. Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age.

Author

Merid, Simon Kebede, Novoloaca, Alexei, Sharp, Gemma C, Küpers, Leanne K, Kho, Alvin T, Roy, Ritu, Gao, Lu, Annesi-Maesano, Isabella, Jain, Pooja, Plusquin, Michelle, Kogevinas, Manolis, Allard, Catherine, Vehmeijer, Florianne O, Kazmi, Nabila, Salas, Lucas A, Rezwan, Faisal I, Zhang, Hongmei, Sebert, Sylvain, Czamara, Darina, Rifas-Shiman, Sheryl L, Melton, Phillip E, Lawlor, Debbie A, Pershagen, Göran, Breton, Carrie V, Huen, Karen, Baiz, Nour, Gagliardi, Luigi, Nawrot, Tim S, Corpeleijn, Eva, Perron, Patrice, Duijts, Liesbeth, Nohr, Ellen Aagaard, Bustamante, Mariona, Ewart, Susan L, Karmaus, Wilfried, Zhao, Shanshan, Page, Christian M, Herceg, Zdenko, Jarvelin, Marjo-Riitta, Lahti, Jari, Baccarelli, Andrea A, Anderson, Denise, Kachroo, Priyadarshini, Relton, Caroline L, Bergström, Anna, Eskenazi, Brenda, Soomro, Munawar Hussain, Vineis, Paolo, Snieder, Harold, Bouchard, Luigi, Jaddoe, Vincent W, Sørensen, Thorkild IA, Vrijheid, Martine, Arshad, S Hasan, Holloway, John W, Håberg, Siri E, Magnus, Per, Dwyer, Terence, Binder, Elisabeth B, DeMeo, Dawn L, Vonk, Judith M, Newnham, John, Tantisira, Kelan G, Kull, Inger, Wiemels, Joseph L, Heude, Barbara, Sunyer, Jordi, Nystad, Wenche, Munthe-Kaas, Monica C, Räikkönen, Katri, Oken, Emily, Huang, Rae-Chi, Weiss, Scott T, Antó, Josep Maria, Bousquet, Jean, Kumar, Ashish, Söderhäll, Cilla, Almqvist, Catarina, Cardenas, Andres, Gruzieva, Olena, Xu, Cheng-Jian, Reese, Sarah E, Kere, Juha, Brodin, Petter, Solomon, Olivia, Wielscher, Matthias, Holland, Nina, Ghantous, Akram, Hivert, Marie-France, Felix, Janine F, Koppelman, Gerard H, London, Stephanie J, and Melén, Erik

Subjects
Humans, Premature Birth, DNA, DNA Methylation, Fetal Development, Adolescent, Child, Child, Preschool, Infant, Newborn, Infant, Premature, Female, Male, Genetic Loci, Epigenome, Development, Epigenetics, Gestational age, Preterm birth, Transcriptomics, Preschool, Infant, Newborn, Premature, Genetics, Clinical Sciences
Abstract

BackgroundPreterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children.MethodsWe performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung.ResultsWe identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P

Published
2020

20. Maternal Infection in Pregnancy and Childhood Leukemia: A Systematic Review and Meta-analysis

Author

He, Jian-Rong, Ramakrishnan, Rema, Hirst, Jane E, Bonaventure, Audrey, Francis, Stephen S, Paltiel, Ora, Håberg, Siri E, Lemeshow, Stanley, Olsen, Sjurdur, Tikellis, Gabriella, Magnus, Per, Murphy, Michael FG, Wiemels, Joseph L, Linet, Martha S, and Dwyer, Terence

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Cancer, Women's Health, Hematology, Maternal Health, Pediatric, Pregnancy, Childhood Leukemia, Pediatric Cancer, Rare Diseases, Child, Female, Global Health, Humans, Incidence, Leukemia, Pregnancy Complications, Infectious, Prenatal Exposure Delayed Effects, Risk Factors, Prenatal, childhood cancer, in utero, Human Movement and Sports Sciences, Paediatrics and Reproductive Medicine, Pediatrics, Paediatrics
Abstract

ObjectiveTo summarize the published evidence regarding the association between maternal infection during pregnancy and childhood leukemia.Study designIn this systematic review and meta-analysis (PROSPERO number, CRD42018087289), we searched PubMed and Embase to identify relevant studies. We included human studies that reported associations of at least one measure of maternal infection during pregnancy with acute lymphoblastic leukemia (ALL) or all childhood leukemias in the offspring. One reviewer extracted the data first using a standardized form, and the second reviewer independently checked the data for accuracy. Two reviewers used the Newcastle-Ottawa Scale to assess the quality of included studies. We conducted random effects meta-analyses to pool the ORs of specific type of infection on ALL and childhood leukemia.ResultsThis review included 20 studies (ALL, n = 15; childhood leukemia, n = 14) reported in 32 articles. Most (>65%) included studies reported a positive association between infection variables and ALL or childhood leukemia. Among specific types of infection, we found that influenza during pregnancy was associated with higher risk of ALL (pooled OR, 3.64; 95% CI, 1.34-9.90) and childhood leukemia (pooled OR, 1.77; 95% CI, 1.01-3.11). Varicella (pooled OR, 10.19; 95% CI, 1.98-52.39) and rubella (pooled OR, 2.79; 95% CI, 1.16-6.71) infections were also associated with higher childhood leukemia risk.ConclusionsOur findings suggest that maternal infection during pregnancy may be associated with a higher risk of childhood leukemia.

Published
2020

22. MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort

Author

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, and Player, Jon

Subjects
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
Abstract

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.

Published
2019

23. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Author

Küpers, Leanne K, Monnereau, Claire, Sharp, Gemma C, Yousefi, Paul, Salas, Lucas A, Ghantous, Akram, Page, Christian M, Reese, Sarah E, Wilcox, Allen J, Czamara, Darina, Starling, Anne P, Novoloaca, Alexei, Lent, Samantha, Roy, Ritu, Hoyo, Cathrine, Breton, Carrie V, Allard, Catherine, Just, Allan C, Bakulski, Kelly M, Holloway, John W, Everson, Todd M, Xu, Cheng-Jian, Huang, Rae-Chi, van der Plaat, Diana A, Wielscher, Matthias, Merid, Simon Kebede, Ullemar, Vilhelmina, Rezwan, Faisal I, Lahti, Jari, van Dongen, Jenny, Langie, Sabine AS, Richardson, Tom G, Magnus, Maria C, Nohr, Ellen A, Xu, Zongli, Duijts, Liesbeth, Zhao, Shanshan, Zhang, Weiming, Plusquin, Michelle, DeMeo, Dawn L, Solomon, Olivia, Heimovaara, Joosje H, Jima, Dereje D, Gao, Lu, Bustamante, Mariona, Perron, Patrice, Wright, Robert O, Hertz-Picciotto, Irva, Zhang, Hongmei, Karagas, Margaret R, Gehring, Ulrike, Marsit, Carmen J, Beilin, Lawrence J, Vonk, Judith M, Jarvelin, Marjo-Riitta, Bergström, Anna, Örtqvist, Anne K, Ewart, Susan, Villa, Pia M, Moore, Sophie E, Willemsen, Gonneke, Standaert, Arnout RL, Håberg, Siri E, Sørensen, Thorkild IA, Taylor, Jack A, Räikkönen, Katri, Yang, Ivana V, Kechris, Katerina, Nawrot, Tim S, Silver, Matt J, Gong, Yun Yun, Richiardi, Lorenzo, Kogevinas, Manolis, Litonjua, Augusto A, Eskenazi, Brenda, Huen, Karen, Mbarek, Hamdi, Maguire, Rachel L, Dwyer, Terence, Vrijheid, Martine, Bouchard, Luigi, Baccarelli, Andrea A, Croen, Lisa A, Karmaus, Wilfried, Anderson, Denise, de Vries, Maaike, Sebert, Sylvain, Kere, Juha, Karlsson, Robert, Arshad, Syed Hasan, Hämäläinen, Esa, Routledge, Michael N, Boomsma, Dorret I, Feinberg, Andrew P, Newschaffer, Craig J, Govarts, Eva, Moisse, Matthieu, Fallin, M Daniele, Melén, Erik, and Prentice, Andrew M

Subjects
Fetus, Humans, Prenatal Exposure Delayed Effects, Birth Weight, Folic Acid, DNA, Body Mass Index, Smoking, DNA Methylation, Epigenesis, Genetic, CpG Islands, Fetal Development, Pregnancy, Genome, Human, Adolescent, Adult, Child, Infant, Newborn, Female, Male, Genome-Wide Association Study, Epigenesis, Genetic, Genome, Human, Infant, Newborn
Abstract

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni

Published
2019

25. Body-mass index trajectories from childhood to mid-adulthood and their sociodemographic predictors: Evidence from the International Childhood Cardiovascular Cohort (i3C) Consortium

Author

Cleland, Verity, Tian, Jing, Buscot, Marie-Jeanne, Magnussen, Costan G., Bazzano, Lydia, Burns, Trudy L., Daniels, Stephen, Dwyer, Terence, Hutri-Kahonen, Nina, Ikonen, Johanna, Jacobs, David, Juonala, Markus, Prineas, Ronald, Raitakari, Olli, Sinaiko, Alan, Steinberger, Julia, Urbina, Elaine M., Woo, Jessica G., and Venn, Alison

Published
2022
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27. Predictors in Youth of Adult Cardiovascular Events.

Author

Nuotio, Joel, Laitinen, Tomi T., Magnussen, Costan G., Sinaiko, Alan R., Bazzano, Lydia A., Daniels, Stephen R., Jacobs Jr, David R., Kartiosuo, Noora, Koskinen, Juha, Burgner, David P., Kähönen, Mika, Raitakari, Olli T., Steinberger, Julia, Urbina, Elaine M., Venn, Alison J., Viikari, Jorma S. A., Woo, Jessica G., Dwyer, Terence, and Juonala, Markus

Published
2024
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28. Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts

Author

Paluch, Amanda E, Bajpai, Shivangi, Bassett, David R, Carnethon, Mercedes R, Ekelund, Ulf, Evenson, Kelly R, Galuska, Deborah A, Jefferis, Barbara J, Kraus, William E, Lee, I-Min, Matthews, Charles E, Omura, John D, Patel, Alpa V, Pieper, Carl F, Rees-Punia, Erika, Dallmeier, Dhayana, Klenk, Jochen, Whincup, Peter H, Dooley, Erin E, Pettee Gabriel, Kelley, Palta, Priya, Pompeii, Lisa A, Chernofsky, Ariel, Larson, Martin G, Vasan, Ramachandran S, Spartano, Nicole, Ballin, Marcel, Nordström, Peter, Nordström, Anna, Anderssen, Sigmund A, Hansen, Bjørge H, Cochrane, Jennifer A, Dwyer, Terence, Wang, Jing, Ferrucci, Luigi, Liu, Fangyu, Schrack, Jennifer, Urbanek, Jacek, Saint-Maurice, Pedro F, Yamamoto, Naofumi, Yoshitake, Yutaka, Newton, Robert L, Jr, Yang, Shengping, Shiroma, Eric J, and Fulton, Janet E

Published
2022
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29. Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium

Author

Nuotio, Joel, Laitinen, Tomi T., Sinaiko, Alan R., Woo, Jessica G., Urbina, Elaine M., Jacobs, Jr, David R., Steinberger, Julia, Prineas, Ronald J., Sabin, Matthew A., Burgner, David P., Minn, Heikki, Burns, Trudy L., Bazzano, Lydia A., Venn, Alison J., Viikari, Jorma S. A., Hutri-Kähönen, Nina, Daniels, Stephen R., Raitakari, Olli T., Magnussen, Costan G., Juonala, Markus, and Dwyer, Terence

Published
2022
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31. Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes

Author

Thomas, Nancy E, Edmiston, Sharon N, Orlow, Irene, Kanetsky, Peter A, Luo, Li, Gibbs, David C, Parrish, Eloise A, Hao, Honglin, Busam, Klaus J, Armstrong, Bruce K, 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, Conway, Kathleen, Begg, Colin, Roy, Pampa, Reiner, Anne, Leong, Siok, Guerrero, Sergio Corrales, Sadeghi, Keimya, Boyce, Tawny W, Venn, Alison, Tucker, Paul, Marrett, Loraine D, From, Lynn, Huang, Shu-Chen, Groben, Pamela A, Parrish, Eloise, Frank, Jill S, Rebbeck, Timothy R, Taylor, Julia Lee, and Madronich, Sasha

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Cancer, Genetic Testing, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Female, GTP Phosphohydrolases, Genetic Association Studies, Genotype, Group VI Phospholipases A2, Humans, Interferon Regulatory Factors, Male, Melanoma, Membrane Proteins, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins B-raf, Risk, Skin Neoplasms, GEM Study Group, Clinical Sciences, Dermatology & Venereal Diseases, Clinical sciences
Abstract

BRAF and NRAS mutations arise early in melanoma development, but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma Study, 1,223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms identified as low-penetrant melanoma-risk variants. We used multinomial logistic regression to simultaneously examine each single-nucleotide polymorphism's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features. IRF4 rs12203592*T was associated with BRAF V600E (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.43-0.79) and V600K (OR = 0.65, 95% CI = 0.41-1.03), but not BRAF other or NRAS+ melanoma. A global test of etiologic heterogeneity (Pglobal = 0.001) passed false discovery (Pglobal = 0.0026). PLA2G6 rs132985*T was associated with BRAF V600E (OR = 1.32, 95% CI = 1.05-1.67) and BRAF other (OR = 1.82, 95% CI = 1.11-2.98), but not BRAF V600K or NRAS+ melanoma. The test for etiologic heterogeneity (Pglobal) was 0.005. The IRF4 rs12203592 associations were slightly attenuated after adjustment for melanoma-risk phenotypes. The PLA2G6 rs132985 associations were independent of phenotypes. IRF4 and PLA2G6 inherited genotypes may influence melanoma BRAF/NRAS subtype development.

Published
2018

32. The interaction between vitamin D receptor polymorphisms and sun exposure around time of diagnosis influences melanoma survival

Author

Orlow, Irene, Shi, Yang, Kanetsky, Peter A, Thomas, Nancy E, Luo, Li, Corrales‐Guerrero, Sergio, Cust, Anne E, Sacchetto, Lidia, Zanetti, Roberto, Rosso, Stefano, Armstrong, Bruce K, Dwyer, Terence, Venn, Alison, Gallagher, Richard P, Gruber, Stephen B, Marrett, Loraine D, Anton‐Culver, Hoda, Busam, Klaus, Begg, Colin B, Berwick, Marianne, and Group, the GEM Study

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Climate-Related Exposures and Conditions, Prevention, Nutrition, Genetics, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Melanoma, Polymorphism, Single Nucleotide, Receptors, Calcitriol, Risk Factors, Sunlight, Survival Analysis, exposure, haplotype, interaction, melanoma, polymorphism, SNP, survival, UVB, vitamin D receptor, GEM Study Group, Biological Sciences, Medical and Health Sciences, Dermatology & Venereal Diseases, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Evidence on the relationship between the vitamin D pathway and outcomes in melanoma is growing, although it is not always clear. We investigated the impact of measured levels of sun exposure at diagnosis on associations of vitamin D receptor gene (VDR) polymorphisms and melanoma death in 3336 incident primary melanoma cases. Interactions between six SNPs and a common 3'-end haplotype were significant (p

Published
2018

33. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author

Felix, Janine F, Joubert, Bonnie R, Baccarelli, Andrea A, Sharp, Gemma C, Almqvist, Catarina, Annesi-Maesano, Isabella, Arshad, Hasan, Baïz, Nour, Bakermans-Kranenburg, Marian J, Bakulski, Kelly M, Binder, Elisabeth B, Bouchard, Luigi, Breton, Carrie V, Brunekreef, Bert, Brunst, Kelly J, Burchard, Esteban G, Bustamante, Mariona, Chatzi, Leda, Munthe-Kaas, Monica Cheng, Corpeleijn, Eva, Czamara, Darina, Dabelea, Dana, Smith, George Davey, De Boever, Patrick, Duijts, Liesbeth, Dwyer, Terence, Eng, Celeste, Eskenazi, Brenda, Everson, Todd M, Falahi, Fahimeh, Fallin, M Daniele, Farchi, Sara, Fernandez, Mariana F, Gao, Lu, Gaunt, Tom R, Ghantous, Akram, Gillman, Matthew W, Gonseth, Semira, Grote, Veit, Gruzieva, Olena, Håberg, Siri E, Herceg, Zdenko, Hivert, Marie-France, Holland, Nina, Holloway, John W, Hoyo, Cathrine, Hu, Donglei, Huang, Rae-Chi, Huen, Karen, Järvelin, Marjo-Riitta, Jima, Dereje D, Just, Allan C, Karagas, Margaret R, Karlsson, Robert, Karmaus, Wilfried, Kechris, Katerina J, Kere, Juha, Kogevinas, Manolis, Koletzko, Berthold, Koppelman, Gerard H, Küpers, Leanne K, Ladd-Acosta, Christine, Lahti, Jari, Lambrechts, Nathalie, Langie, Sabine AS, Lie, Rolv T, Liu, Andrew H, Magnus, Maria C, Magnus, Per, Maguire, Rachel L, Marsit, Carmen J, McArdle, Wendy, Melén, Erik, Melton, Phillip, Murphy, Susan K, Nawrot, Tim S, Nisticò, Lorenza, Nohr, Ellen A, Nordlund, Björn, Nystad, Wenche, Oh, Sam S, Oken, Emily, Page, Christian M, Perron, Patrice, Pershagen, Göran, Pizzi, Costanza, Plusquin, Michelle, Raikkonen, Katri, Reese, Sarah E, Reischl, Eva, Richiardi, Lorenzo, Ring, Susan, Roy, Ritu P, Rzehak, Peter, Schoeters, Greet, Schwartz, David A, Sebert, Sylvain, Snieder, Harold, Sørensen, Thorkild IA, and Starling, Anne P

Subjects
Epidemiology, Public Health, Health Sciences, Statistics, Mathematical Sciences, Child Health, Cohort Studies, DNA Methylation, Environmental Pollution, Epigenesis, Genetic, Female, Folic Acid, Humans, Infant, Newborn, Maternal Exposure, Maternal Health, Pregnancy, Prenatal Exposure Delayed Effects, Public Health and Health Services, Public health
Published
2018

34. The multiple sclerosis risk allele within the AHI1 gene is associated with relapses in children and adults

Author

Graves, Jennifer S, Barcellos, Lisa F, Simpson, Steve, Belman, Anita, Lin, Rui, Taylor, Bruce V, Ponsonby, Anne-Louise, Dwyer, Terence, Krupp, Lauren, Waubant, Emmanuelle, and van der Mei, Ingrid AF

Subjects
Biomedical and Clinical Sciences, Neurosciences, Pediatric, Genetics, Clinical Research, Neurodegenerative, Brain Disorders, Multiple Sclerosis, Autoimmune Disease, Prevention, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Adolescent, Adult, Alleles, California, Child, Female, Genetic Predisposition to Disease, Genotype, Humans, Longitudinal Studies, Male, Middle Aged, New York, Polymorphism, Single Nucleotide, Recurrence, Tasmania, Multiple sclerosis
Abstract

BackgroundWhile common variant non-HLA (human leukocyte antigen) alleles have been associated with MS risk, their role in disease course is less clear. We sought to determine whether established multiple sclerosis (MS) genetic susceptibility factors are associated with relapse rate in children and an independent cohort of adults with MS.MethodsGenotyping was performed for 182 children with MS or clinically isolated syndrome with high risk for MS from two Pediatric MS Centers. They were prospectively followed for relapses. Fifty-two non-HLA MS susceptibility single nucleotide polymorphisms (SNPs) were evaluated for association with relapse rate. Cox regression models were adjusted for sex, genetic ancestry, disease-modifying therapy (DMT), 25-OH vitamin D level and HLA-DRB1*15:01/03 status. Investigation of pediatric subject SNP results was performed using a second cohort of 141 adult MS subjects of Northern European ancestry from the Southern Tasmanian Multiple Sclerosis Longitudinal Study.ResultsFor pediatric subjects, 408 relapses were captured over 622 patient-years of follow-up. Four non-HLA risk SNPs (rs11154801, rs650258, rs12212193, rs2303759) were associated with relapses (p < 0.01) in the pediatric subjects. After adjustment for genetic ancestry, sex, age, vitamin D level, DMT use and HLA-DRB1*15 status, having two copies of the MS risk allele within AHI1 (rs11154801) was associated with increased relapses among children (HR = 1.75,95%CI = 1.18-2.48, p = 0.006) and this result was also observed among adults (HR = 1.81,95%CI = 1.05-3.03, p = 0.026).ConclusionsOur results suggest that the MS genetic risk variant within the gene AHI1 may contribute to disease course in addition to disease susceptibility.

Published
2018

36. Non–High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events

Author

Wu, Feitong, primary, Jacobs, David R., additional, Daniels, Stephen R., additional, Kähönen, Mika, additional, Woo, Jessica G., additional, Sinaiko, Alan R., additional, Viikari, Jorma S. A., additional, Bazzano, Lydia A., additional, Steinberger, Julia, additional, Urbina, Elaine M., additional, Venn, Alison J., additional, Raitakari, Olli T., additional, Dwyer, Terence, additional, Juonala, Markus, additional, and Magnussen, Costan G., additional

Published
2024
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39. Associations of MC1R Genotype and Patient Phenotypes with BRAF and NRAS Mutations in Melanoma

Author

Thomas, Nancy E, Edmiston, Sharon N, Kanetsky, Peter A, Busam, Klaus J, Kricker, Anne, Armstrong, Bruce K, Cust, Anne E, Anton-Culver, Hoda, Gruber, Stephen B, Luo, Li, Orlow, Irene, Reiner, Anne S, Gallagher, Richard P, Zanetti, Roberto, Rosso, Stefano, Sacchetto, Lidia, Dwyer, Terence, Parrish, Eloise A, Hao, Honglin, Gibbs, David C, Frank, Jill S, Ollila, David W, Begg, Colin B, Berwick, Marianne, Conway, Kathleen, Roy, Pampa, Patel, Himali, Paine, Susan, Venn, Alison, Tucker, Paul, Marrett, Loraine D, From, Lynn, Huang, Shu-Chen, Groben, Pamela A, Parrish, Eloise, Bramson, Jennifer I, Rebbeck, Timothy R, Taylor, Julia Lee, and Madronich, Sasha

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Adult, Aged, Australia, Female, GTP Phosphohydrolases, Genotype, Humans, Male, Melanoma, Membrane Proteins, Middle Aged, Mutation, Phenotype, Proto-Oncogene Proteins B-raf, Receptor, Melanocortin, Type 1, Skin Neoplasms, United States, GEM Study Group, Clinical Sciences, Dermatology & Venereal Diseases, Clinical sciences
Abstract

Associations of MC1R with BRAF mutations in melanoma have been inconsistent between studies. We sought to determine for 1,227 participants in the international population-based Genes, Environment, and Melanoma (GEM) study whether MC1R and phenotypes were associated with melanoma BRAF/NRAS subtypes. We used logistic regression adjusted by age, sex, and study design features and examined effect modifications. BRAF+ were associated with younger age, blond/light brown hair, increased nevi, and less freckling, and NRAS+ with older age relative to the wild type (BRAF-/NRAS-) melanomas (all P < 0.05). Comparing specific BRAF subtypes to the wild type, BRAF V600E was associated with younger age, blond/light brown hair, and increased nevi and V600K with increased nevi and less freckling (all P < 0.05). MC1R was positively associated with BRAF V600E cases but only among individuals with darker phototypes or darker hair (Pinteraction < 0.05) but inversely associated with BRAF V600K (Ptrend = 0.006) with no significant effect modification by phenotypes. These results support distinct etiologies for BRAF V600E, BRAF V600K, NRAS+, and wild-type melanomas. MC1R's associations with BRAF V600E cases limited to individuals with darker phenotypes indicate that MC1R genotypes specifically provide information about BRAF V600E melanoma risk in those not considered high risk based on phenotype. Our results also suggest that melanin pathways deserve further study in BRAF V600E melanomagenesis.

Published
2017

40. Association of Incident Amelanotic Melanoma With Phenotypic Characteristics, MC1R Status, and Prior Amelanotic Melanoma

Author

Vernali, Steven, Waxweiler, Weston T, Dillon, Patrick M, Kanetsky, Peter A, Orlow, Irene, Luo, Li, Busam, Klaus J, Kricker, Anne, Armstrong, Bruce K, Anton-Culver, Hoda, Gruber, Stephen B, Gallagher, Richard P, Zanetti, Roberto, Rosso, Stefano, Sacchetto, Lidia, Dwyer, Terence, Cust, Anne E, Ollila, David W, Begg, Colin B, Berwick, Marianne, and Thomas, Nancy E

Subjects
Genetics, Clinical Research, Climate-Related Exposures and Conditions, Cancer, Adult, Aged, Cohort Studies, Female, Humans, Logistic Models, Male, Melanoma, Amelanotic, Middle Aged, Phenotype, Pigmentation, Receptor, Melanocortin, Type 1, Skin Neoplasms, GEM Study Group, Clinical Sciences, Oncology and Carcinogenesis
Abstract

ImportanceWe previously reported that survival is poorer from histopathologically amelanotic than pigmented melanoma because of more advanced stage at diagnosis. Identifying patients at risk of amelanotic melanoma might enable earlier diagnosis and improved survival; however, the phenotypic characteristics and underlying genetics associated with amelanotic melanoma are unknown.ObjectiveTo determine whether phenotypic characteristics, carriage of MC1R variants, and history of amelanotic melanoma are associated with histopathologically amelanotic melanoma.Design, setting, and participantsThe Genes, Environment, and Melanoma (GEM) study is an international cohort study that enrolled patients with incident primary cutaneous melanomas from population-based and hospital-based cancer registries (1998 to 2003). The GEM participants included here were 2387 patients with data for phenotypes, MC1R genotype, and primary melanomas scored for histopathologic pigmentation. Of these 2387 patients with incident melanomas scored for pigmentation, 527 had prior primary melanomas also scored for pigmentation.Main outcomes and measuresAssociations of phenotypic characteristics (freckles, nevi, phenotypic index) and MC1R status with incident amelanotic melanomas were evaluated using logistic regression models adjusted for age, sex, study center, and primary status (single or multiple primary melanoma); odds ratios (ORs) and 95% CIs are reported. Association of histopathologic pigmentation between incident and prior melanomas was analyzed using an exact logistic regression model.ResultsThis study included 2387 patients (1065 women, 1322 men; mean [SD] age at diagnosis, 58.3 [16.1] years) and 2917 primary melanomas. In a multivariable model including phenotypic characteristics, absence of back nevi, presence of many freckles, and a sun-sensitive phenotypic index were independently associated with amelanotic melanoma. Carriage of MC1R variants was associated with amelanotic melanoma but lost statistical significance in a model with phenotype. Further, patients with incident primary amelanotic melanomas were more likely to have had a prior primary amelanotic melanoma (OR, 4.62; 95% CI, 1.25-14.13) than those with incident primary pigmented melanomas.Conclusions and relevanceAbsence of back nevi, presence of many freckles, a sun-sensitive phenotypic index, and prior amelanotic melanoma increase odds for development of amelanotic melanoma. An increased index of suspicion for melanoma in presenting nonpigmented lesions and more careful examination for signs of amelanotic melanoma during periodic skin examination in patients at increased odds of amelanotic melanoma might lead to earlier diagnosis and improved survival.

Published
2017

44. Association of Ideal Cardiovascular Health in Youth with Cancer Risk in Adulthood: A Cardiovascular Risk in Young Finns Study.

Author

Niemelä, Jussi, Nuotio, Joel, Laitinen, Tomi T., Kähönen, Mika, Hutri, Nina, Lehtimäki, Terho, Jokinen, Eero, Tossavainen, Päivi, Laitinen, Tomi P., Heinonen, Olli J., Dwyer, Terence, Pahkala, Katja, Rovio, Suvi P., Viikari, Jorma, Raitakari, Olli, and Juonala, Markus

Abstract

Background: Lifestyle factors may affect cancer risk. This study aimed to identify whether the American Heart Association ideal cardiovascular health (ICH) score and its individual variables in youth are associated with subsequent cancer incidence. Methods: This study comprised participants of the Cardiovascular Risk in Young Finns Study free of cancer at the analysis baseline in 1986 (n = 1,873). The baseline age was 12 to 24 years, and the follow-up occurred between 1986 and 2018. Results: Among 1,873 participants (mean age 17.3 ± 4.1 years; 53.4% females at baseline), 72 incident cancer cases occurred during the follow-up (mean follow-up time 31.4 ± 3.4 years). Baseline ICH score was not associated with future cancer risk (HR, 0.96; 95% confidence interval, 0.78-1.12 per 1-point increment). Of individual ICH score variables, ideal physical activity (PA) was inversely associated with cancer incidence [age- and sex-adjusted HR, 0.45 (0.23-0.88) per 1-category change (nonideal/ideal)] and remained significant in the multivariable-adjusted model, including body mass index, smoking, diet, and socioeconomic status. A continuous PA index at ages 9 to 24 years and moderate-to-vigorous PA in youth were also related to decreased cancer incidence (P < 0.05). Body mass index, smoking, diet, total cholesterol, glucose, and blood pressure were not related to cancer risk. Of the dietary components, meat consumption was associated with cancer incidence (P = 0.023). Conclusions: These findings indicate that higher PA levels in youth are associated with a reduced subsequent cancer incidence, whereas the American Heart Association's ICH score in youth does not. Impact: This finding supports efforts to promote a healthy lifestyle and encourages PA during childhood, yielding a subsequent healthier life. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Skin Prick Test Predictive Values for the Outcome of Cashew Challenges in Children

Author

Dwyer, Terence, Lowe, Adrian, Wake, Melissa, Robertson, Colin, Sawyer, Susan, Patton, George, Douglass, Jo, Vuillermin, Peter, McWilliam, Vicki, Peters, Rachel L., Allen, Katrina J., Dharmage, Shyamali C., Ponsonby, Anne-Louise, Tang, Mimi L.K., Smart, Joanne, Perrett, Kirsten, Tey, Dean, Robinson, Marnie, Taranto, Mark, Koplin, Jennifer J., and Gurrin, Lyle C.

Published
2020
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50. Variants in autophagy‐related genes and clinical characteristics in melanoma: a population‐based study

Author

White, Kirsten AM, Luo, Li, Thompson, Todd A, Torres, Salina, Hu, Chien‐An Andy, Thomas, Nancy E, Lilyquist, Jenna, Anton‐Culver, Hoda, Gruber, Stephen B, From, Lynn, Busam, Klaus J, Orlow, Irene, Kanetsky, Peter A, Marrett, Loraine D, Gallagher, Richard P, Sacchetto, Lidia, Rosso, Stefano, Dwyer, Terence, Cust, Anne E, Begg, Colin B, Berwick, Marianne, Mujumdar, Urvi, Roy, Pampa, Armstrong, Bruce, Kricker, Anne, Litchfield, Melisa, Tucker, Paul, Venn, Alison, Stephens, Nicola, Switzer, Teresa, Marrett, Loraine, Theis, Elizabeth, Chowdhury, Noori, Vanasse, Louise, Zanetti, Roberto, Sacerdote, Carlotta, Leighton, Nancy, Jeter, Joanne, Klotz, Judith, Wilcox, Homer, Weiss, Helen, Mattingly, Dianne, Player, Jon, Rebbeck, Timothy, Walker, Amy, Panossian, Saarene, Taylor, Julia Lee, and Madronich, Sasha

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Clinical Research, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, 2.1 Biological and endogenous factors, Adult, Aged, Alleles, Autophagy, Autophagy-Related Proteins, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Male, Melanoma, Middle Aged, Models, Biological, Neoplasm Staging, Odds Ratio, Polymorphism, Single Nucleotide, Population Surveillance, ATG16L1, autophagy, melanoma, polymorphism, SNP, GEM Study Group, ATG16L1, SNP, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression.

Published
2016

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