BACKGROUND: The association of melanoma with HLA class II loci is under extensive debate. Different investigators have found discrepant results due to, at least in part, sample size, patient series heterogeneity, choice of control population and differences in the techniques employed for the detection of HLA antigens and alleles. OBJECTIVES: This study was designed to analyse the possible association of melanoma with HLA class II loci with regard to different clinic pathological factors and to investigate other risk factors for melanoma susceptibility, such as HLA homozygosity. PATIENTS AND METHODS: HLA-DRB1, -DQA1 and -DQB1 genotyping was performed for 117 eastern Spanish patients presenting with primary melanoma. RESULTS: Although there were no significant alterations in the phenotypic frequencies of HLA-DQA1, -DQB1 or -DRB1 alleles in any subgroup of patients when compared with controls, patients exhibited a statistically significant increase in HLA-DQA1 homozygosity rate. This DQA1 homozygosity-specific association was particularly dependent on some features in melanoma patients such as light hair colour, skin type I or II, early age at diagnosis, absence of atypical naevi, or abscence of atypical naevus syndrome phenotype (aetiological fractions about 10-20%). Analysis of homozygosity for single DQA1 alleles showed an increased homozygosity rate for DQA1*0505 and DQA1*0301 in comparison with controls. These DQA1 alleles are in strong linkage disequilibrium with DQB1*0301 in white populations, and DQB1*0301 homozygous individuals were significantly increased in red in or fair-haired patients (relative risk 5.65). CONCLUSIONS: Our results indicate that the contribution of HLA class II alleles to primary melanoma incidence is not significant in the Spanish population. However, homozygosity for the HLA-DQA1 locus (and, perhaps, for the HLA-DQB1*0301 allele) might be considered a potential risk factor for developing melanoma depending on the person's genetic background and, perhaps, on certain environmental conditions.
BACKGROUND: The association of melanoma with HLA class II loci is under extensive debate. Different investigators have found discrepant results due to, at least in part, sample size, patient series heterogeneity, choice of control population and differences in the techniques employed for the detection of HLA antigens and alleles. OBJECTIVES: This study was designed to analyse the possible association of melanoma with HLA class II loci with regard to different clinic pathological factors and to investigate other risk factors for melanoma susceptibility, such as HLA homozygosity. PATIENTS AND METHODS: HLA-DRB1, -DQA1 and -DQB1 genotyping was performed for 117 eastern Spanish patients presenting with primary melanoma. RESULTS: Although there were no significant alterations in the phenotypic frequencies of HLA-DQA1, -DQB1 or -DRB1 alleles in any subgroup of patients when compared with controls, patients exhibited a statistically significant increase in HLA-DQA1 homozygosity rate. This DQA1 homozygosity-specific association was particularly dependent on some features in melanomapatients such as light hair colour, skin type I or II, early age at diagnosis, absence of atypical naevi, or abscence of atypical naevus syndrome phenotype (aetiological fractions about 10-20%). Analysis of homozygosity for single DQA1 alleles showed an increased homozygosity rate for DQA1*0505 and DQA1*0301 in comparison with controls. These DQA1 alleles are in strong linkage disequilibrium with DQB1*0301 in white populations, and DQB1*0301 homozygous individuals were significantly increased in red in or fair-haired patients (relative risk 5.65). CONCLUSIONS: Our results indicate that the contribution of HLA class II alleles to primary melanoma incidence is not significant in the Spanish population. However, homozygosity for the HLA-DQA1 locus (and, perhaps, for the HLA-DQB1*0301 allele) might be considered a potential risk factor for developing melanoma depending on the person's genetic background and, perhaps, on certain environmental conditions.
Authors: Miriam Potrony; Celia Badenas; Paula Aguilera; Joan Anton Puig-Butille; Cristina Carrera; Josep Malvehy; Susana Puig Journal: Ann Transl Med Date: 2015-09
Authors: Alexander J Stratigos; Paola Ghiorzo; Kevin M Brown; Susana Puig; Eduardo Nagore; Maria Teresa Landi; D Timothy Bishop; Stuart MacGregor; Mitchell J Machiela; Myriam Brossard; Donato Calista; Jiyeon Choi; Maria Concetta Fargnoli; Tongwu Zhang; Monica Rodolfo; Adam J Trower; Chiara Menin; Jacobo Martinez; Andreas Hadjisavvas; Lei Song; Irene Stefanaki; Richard Scolyer; Rose Yang; Alisa M Goldstein; Miriam Potrony; Katerina P Kypreou; Lorenza Pastorino; Paola Queirolo; Cristina Pellegrini; Laura Cattaneo; Matthew Zawistowski; Pol Gimenez-Xavier; Arantxa Rodriguez; Lisa Elefanti; Siranoush Manoukian; Licia Rivoltini; Blair H Smith; Maria A Loizidou; Laura Del Regno; Daniela Massi; Mario Mandala; Kiarash Khosrotehrani; Lars A Akslen; Christopher I Amos; Per A Andresen; Marie-Françoise Avril; Esther Azizi; H Peter Soyer; Veronique Bataille; Bruna Dalmasso; Lisa M Bowdler; Kathryn P Burdon; Wei V Chen; Veryan Codd; Jamie E Craig; Tadeusz Dębniak; Mario Falchi; Shenying Fang; Eitan Friedman; Sarah Simi; Pilar Galan; Zaida Garcia-Casado; Elizabeth M Gillanders; Scott Gordon; Adele Green; Nelleke A Gruis; Johan Hansson; Mark Harland; Jessica Harris; Per Helsing; Anjali Henders; Marko Hočevar; Veronica Höiom; David Hunter; Christian Ingvar; Rajiv Kumar; Julie Lang; G Mark Lathrop; Jeffrey E Lee; Xin Li; Jan Lubiński; Rona M Mackie; Maryrose Malt; Josep Malvehy; Kerrie McAloney; Hamida Mohamdi; Anders Molven; Eric K Moses; Rachel E Neale; Srdjan Novaković; Dale R Nyholt; Håkan Olsson; Nicholas Orr; Lars G Fritsche; Joan Anton Puig-Butille; Abrar A Qureshi; Graham L Radford-Smith; Juliette Randerson-Moor; Celia Requena; Casey Rowe; Nilesh J Samani; Marianna Sanna; Dirk Schadendorf; Hans-Joachim Schulze; Lisa A Simms; Mark Smithers; Fengju Song; Anthony J Swerdlow; Nienke van der Stoep; Nicole A Kukutsch; Alessia Visconti; Leanne Wallace; Sarah V Ward; Lawrie Wheeler; Richard A Sturm; Amy Hutchinson; Kristine Jones; Michael Malasky; Aurelie Vogt; Weiyin Zhou; Karen A Pooley; David E Elder; Jiali Han; Belynda Hicks; Nicholas K Hayward; Peter A Kanetsky; Chad Brummett; Grant W Montgomery; Catherine M Olsen; Caroline Hayward; Alison M Dunning; Nicholas G Martin; Evangelos Evangelou; Graham J Mann; Georgina Long; Paul D P Pharoah; Douglas F Easton; Jennifer H Barrett; Anne E Cust; Goncalo Abecasis; David L Duffy; David C Whiteman; Helen Gogas; Arcangela De Nicolo; Margaret A Tucker; Julia A Newton-Bishop; Ketty Peris; Stephen J Chanock; Florence Demenais; Jianxin Shi; Mark M Iles; Matthew H Law Journal: Nat Genet Date: 2020-04-27 Impact factor: 38.330