Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study

被引：13

作者：

Kleinstern, Geffen ^{[1
]}

Camp, Nicola J. ^{[2
,3
]}

Berndt, Sonja I. ^{[4
]}

Birmann, Brenda M. ^{[5
,6
]}

Nieters, Alexandra ^{[7
]}

Bracci, Paige M. ^{[8
]}

McKay, James D. ^{[9
]}

Ghesquieres, Herv E. ^{[10
]}

Lan, Qing ^{[4
]}

Hjalgrim, Henrik ^{[11
]}

Benavente, Yolanda ^{[12
,13
]}

Monnereau, Alain ^{[14
]}

Wang, Sophia S. ^{[15
]}

Zhang, Yawei ^{[16
]}

Purdue, Mark P. ^{[4
]}

Zeleniuch-Jacquotte, Anne ^{[17
,18
]}

Giles, Graham G. ^{[19
,20
,21
]}

Vermeulen, Roel ^{[22
]}

Cocco, Pierluigi ^{[23
]}

Albanes, Demetrius ^{[4
]}

Teras, Lauren R. ^{[24
]}

Brooks-Wilson, Angela R. ^{[25
,26
]}

Vajdic, Claire M. ^{[27
]}

Kane, Eleanor ^{[28
]}

Caporaso, Neil E. ^{[4
]}

Smedby, Karin E. ^{[29
]}

Salles, Gilles ^{[10
]}

Vijai, Joseph ^{[30
]}

Chanock, Stephen J. ^{[4
]}

Skibola, Christine F. ^{[31
]}

Rothman, Nathaniel ^{[4
]}

Slager, Susan L. ^{[1
]}

Cerhan, James R. ^{[1
]}

机构：

[1] Mayo Clin, 200 First St SW, Rochester, MN 55905 USA

[2] Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT USA

[3] Univ Utah, Sch Med, Salt Lake City, UT USA

[4] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[5] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[6] Harvard Med Sch, Boston, MA 02115 USA

[7] Univ Freiburg, Med Ctr, Inst Immunodeficiency, Freiburg, Germany

[8] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA

[9] Int Agcy Res Canc, Lyon, France

[10] Univ Claude Bernard Lyon 1, Ctr Hosp Lyon Sud, Dept Hematol, Pierre Benite, France

[11] Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, Copenhagen, Denmark

[12] Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Madrid, Spain

[13] Catalan Inst Oncol ICO IDIBELL, Unit Mol & Genet Epidemiol Infect & Canc, Barcelona, Spain

[14] Ctr Res Epidemiol & Stat Sorbonne Paris Cite CRES, Epidemiol Childhood & Adolescent Canc Grp, Registre Hemopathies Malignes Gironde, Inst Bergonie,INSERM, Paris, France

[15] City Hope Beckman Res Inst, Duarte, CA USA

[16] Yale Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA

[17] NYU Sch Med, Dept Populat Hlth, New York, NY USA

[18] NYU Sch Med, Perlmutter Canc Ctr, New York, NY USA

[19] Canc Council Victoria, Canc Epidemiol Div, Melbourne, Vic, Australia

[20] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia

[21] Monash Univ, Precis Med, Melbourne, Vic, Australia

[22] Univ Med Ctr Utrecht, Utrecht, Netherlands

[23] Univ Cagliari, Occupat Hlth Sect, Dept Med Sci & Publ Hlth, Monserrato, Italy

[24] Amer Canc Soc, Atlanta, GA 30329 USA

[25] BC Canc, Vancouver, BC, Canada

[26] Simon Fraser Univ, Biomed Physiol & Kinesiol, Burnaby, BC, Canada

[27] Univ New South Wales, Ctr Big Data Res Hlth, Sydney, NSW, Australia

[28] Univ York, Dept Hlth Sci, Epidemiol & Canc Stat Grp, York, N Yorkshire, England

[29] Karolinska Inst, Div Clin Epidemiol, Dept Med, Stockholm, Sweden

[30] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY USA

[31] Emory Univ, Atlanta, GA 30322 USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2020年 / 29卷 / 05期

基金：

英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CHOLESTEROL;

D O I：

10.1158/1055-9965.EPI-19-0803

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis. Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated (P < 5 x 10(-8)) with high-density lipoprotein (HDL, n = 164), low-density lipoprotein (LDL, n = 137), total cholesterol (TC, n = 161), and triglycerides (TG, n = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance-weighted method, estimating odds ratios ( OR) per standard deviation and 95% confidence intervals (CI). Results: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00-1.30) and MZL (OR = 1.09; 95% CI, 1.01-1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83-0.99), all at nominal significance (P < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99-1.19; P = 0.087). No associations were noteworthy after adjusting for multiple testing. Conclusions: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes. Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.

引用

页码：1074 / 1078

页数：5

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