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@ARTICLE{Wang:136828,
author = {S. S. Wang and M. Carrington and S. I. Berndt and S. L.
Slager and P. M. Bracci and J. Voutsinas and J. R. Cerhan
and K. E. Smedby and H. Hjalgrim and J. Vijai and L. M.
Morton and R. Vermeulen and O. Paltiel and C. M. Vajdic and
M. S. Linet and A. Nieters and S. de Sanjose and W. Cozen
and E. E. Brown and J. Turner and J. J. Spinelli and T.
Zheng and B. M. Birmann and C. R. Flowers and N. Becker$^*$
and E. A. Holly and E. Kane and D. Weisenburger and M.
Maynadie and P. Cocco and D. Albanes and S. J. Weinstein and
L. R. Teras and W. R. Diver and S. J. Lax and R. C. Travis
and R. Kaaks$^*$ and E. Riboli and Y. Benavente and P.
Brennan and J. McKay and M.-H. Delfau-Larue and B. K. Link
and C. Magnani and M. G. Ennas and G. Latte and A. L.
Feldman and N. W. Doo and G. G. Giles and M. C. Southey and
R. L. Milne and K. Offit and J. Musinsky and A. A. Arslan
and M. P. Purdue and H.-O. Adami and M. Melbye and B.
Glimelius and L. Conde and N. J. Camp and M. Glenn and K.
Curtin and J. Clavel and A. Monnereau and D. G. Cox and H.
Ghesquières and G. Salles and P. Bofetta and L. Foretova
and A. Staines and S. Davis and R. K. Severson and Q. Lan
and A. Brooks-Wilson and M. T. Smith and E. Roman and A.
Kricker and Y. Zhang and P. Kraft and S. J. Chanock and N.
Rothman and P. Hartge and C. F. Skibola},
title = {{HLA} {C}lass {I} and {II} {D}iversity {C}ontributes to the
{E}tiologic {H}eterogeneity of {N}on-{H}odgkin {L}ymphoma
{S}ubtypes.},
journal = {Cancer research},
volume = {78},
number = {14},
issn = {1538-7445},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2018-01266},
pages = {4086 - 4096},
year = {2018},
abstract = {A growing number of loci within the human leukocyte antigen
(HLA) region have been implicated in non-Hodgkin lymphoma
(NHL) etiology. Here, we test a complementary hypothesis of
'heterozygote advantage' regarding the role of HLA and NHL,
whereby HLA diversity is beneficial and homozygous HLA loci
are associated with increased disease risk. HLA alleles at
class I and II loci were imputed from genome-wide
association studies (GWAS) using SNP2HLA for 3,617 diffuse
large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas
(FL), 2,878 chronic lymphocytic leukemia/small lymphocytic
lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and
8,753 controls of European descent. Both DLBCL and MZL risk
were elevated with homozygosity at class I HLA-B and -C loci
(OR DLBCL = 1.31, $95\%$ CI = 1.06-1.60; OR MZL = 1.45,
$95\%$ CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL
= 2.10, $95\%$ CI = 1.24-3.55; OR MZL = 2.10, $95\%$ CI =
0.99-4.45). Increased FL risk was observed with the overall
increase in number of homozygous HLA class II loci (P trend
< 0.0001, FDR = 0.0005). These results support a role for
HLA zygosity in NHL etiology and suggests that distinct
immune pathways may underly the etiology of the different
NHL subtypes.Significance: HLA gene diversity reduces risk
for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96.
©2018 AACR.},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29735552},
pmc = {pmc:PMC6065509},
doi = {10.1158/0008-5472.CAN-17-2900},
url = {https://inrepo02.dkfz.de/record/136828},
}