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GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma
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نویسنده
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smedby k.e. ,foo j.n. ,skibola c.f. ,darabi h. ,conde l. ,hjalgrim h. ,kumar v. ,chang e.t. ,rothman n. ,cerhan j.r. ,brooks-wilson a.r. ,rehnberg e. ,irwan i.d. ,ryder l.p. ,brown p.n. ,bracci p.m. ,agana l. ,riby j. ,cozen w. ,davis s. ,hartge p. ,morton l.m. ,severson r.k. ,wang s.s. ,slager s.l. ,fredericksen z.s. ,novak a.j. ,kay n.e. ,habermann t.m. ,armstrong b. ,kricker a. ,milliken s. ,purdue m.p. ,vajdic c.m. ,boyle p. ,lan q. ,zahm s.h. ,zhang y. ,zheng t. ,leach s. ,spinelli j.j. ,smith m.t. ,chanock s.j. ,padyukov l. ,alfredsson l. ,klareskog l. ,glimelius b. ,melbye m. ,liu e.t. ,adami h.-o. ,humphreys k. ,liu j.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 4
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چکیده
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Non-hodgkin lymphoma (nhl) represents a diverse group of hematological malignancies,of which follicular lymphoma (fl) is a prevalent subtype. a previous genome-wide association study has established a marker,rs10484561 in the human leukocyte antigen (hla) class ii region on 6p21.32 associated with increased fl risk. here,in a three-stage genome-wide association study,starting with a genome-wide scan of 379 fl cases and 791 controls followed by validation in 1,049 cases and 5,790 controls,we identified a second independent fl-associated locus on 6p21.32,rs2647012 (orcombined = 0.64,pcombined = 2×10-21) located 962 bp away from rs10484561 (r2<0.1 in controls). after mutual adjustment,the associations at the two snps remained genome-wide significant (rs2647012:oradjusted = 0.70,padjusted = 4×10-12; rs10484561:oradjusted = 1.64,padjusted = 5×10-15). haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on fl risk. moreover,in a follow-up analysis of the top 6 fl-associated snps in 4,449 cases of other nhl subtypes,rs10484561 was associated with risk of diffuse large b-cell lymphoma (orcombined = 1.36,pcombined = 1.4×10-7). our results reveal the presence of allelic heterogeneity within the hla class ii region influencing fl susceptibility and indicate a possible shared genetic etiology with diffuse large b-cell lymphoma. these findings suggest that the hla class ii region plays a complex yet important role in nhl.
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آدرس
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department of medicine,clinical epidemiology unit,karolinska institutet,stockholm, Sweden, human genetics,genome institute of singapore,a star,singapore, Singapore, division of environmental health sciences,school of public health,university of california berkeley,berkeley,ca, United States, department of medical epidemiology and biostatistics,karolinska institutet,stockholm, Sweden, division of environmental health sciences,school of public health,university of california berkeley,berkeley,ca, United States, department of epidemiology research,statens serum institut,copenhagen, Denmark, human genetics,genome institute of singapore,a star,singapore, Singapore, cancer prevention institute of california,fremont,ca,united states,division of epidemiology,department of health research and policy,stanford university school of medicine,stanford,ca, United States, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md, United States, college of medicine,mayo clinic,rochester,mn, United States, british columbia cancer research center,british columbia cancer agency,vancouver,canada,department of biomedical physiology and kinesiology,simon fraser university,burnaby, Canada, department of medical epidemiology and biostatistics,karolinska institutet,stockholm, Sweden, human genetics,genome institute of singapore,a star,singapore, Singapore, department of clinical immunology,university hospital of copenhagen,copenhagen, Denmark, department of haematology,copenhagen university hospital,copenhagen, Denmark, department of epidemiology and biostatistics,university of california san francisco,san francisco,ca, United States, division of environmental health sciences,school of public health,university of california berkeley,berkeley,ca, United States, division of environmental health sciences,school of public health,university of california berkeley,berkeley,ca, United States, department of preventive medicine,keck school of medicine,university of southern california,los angeles,ca, United States, fred hutchinson cancer research center,seattle,wa,united states,university of washington,seattle,wa, United States, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md, United States, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md, United States, department of family medicine and public health sciences,wayne state university,detroit,mi,united states,karmanos cancer institute,detroit,mi, United States, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md,united states,division of etiology,beckman research institute and the city of hope,duarte,ca, United States, college of medicine,mayo clinic,rochester,mn, United States, college of medicine,mayo clinic,rochester,mn, United States, college of medicine,mayo clinic,rochester,mn, United States, college of medicine,mayo clinic,rochester,mn, United States, college of medicine,mayo clinic,rochester,mn, United States, sydney school of public health,the university of sydney,sydney, Australia, sydney school of public health,the university of sydney,sydney, Australia, department of haematology,st. vincent's hospital,sydney, Australia, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md, United States, university of new south wales cancer research center,prince of wales clinical school,sydney, Australia, international prevention research institute,lyon, France, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md, United States, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md, United States, school of public health,yale university,new haven,ct, United States, school of public health,yale university,new haven,ct, United States, canada's michael smith genome sciences centre,british columbia cancer agency,vancouver, Canada, british columbia cancer research center,british columbia cancer agency,vancouver,canada,school of population and public health,university of british columbia,vancouver, Canada, division of environmental health sciences,school of public health,university of california berkeley,berkeley,ca, United States, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md, United States, rheumatology unit,department of medicine,karolinska institutet and karolinska university hospital solna,stockholm, Sweden, institute of environmental medicine,karolinska institutet,stockholm, Sweden, rheumatology unit,department of medicine,karolinska institutet and karolinska university hospital solna,stockholm, Sweden, department of pathology and oncology,karolinska institutet,stockholm,sweden,department of radiology,oncology,and radiation sciences,uppsala university,uppsala, Sweden, department of epidemiology research,statens serum institut,copenhagen, Denmark, human genetics,genome institute of singapore,a star,singapore, Singapore, department of medical epidemiology and biostatistics,karolinska institutet,stockholm,sweden,department of epidemiology,harvard school of public health,boston,ma, United States, department of medical epidemiology and biostatistics,karolinska institutet,stockholm, Sweden, human genetics,genome institute of singapore,a star,singapore, Singapore
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