Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

被引：51

作者：

Machiela, Mitchell J. ^{[1
]}

Lan, Qing ^{[1
]}

Slager, Susan L. ^{[2
]}

Vermeulen, Roel C. H. ^{[5
,6
]}

Teras, Lauren R. ^{[8
]}

Camp, Nicola J. ^{[9
]}

Cerhan, James R. ^{[2
]}

Spinelli, John J. ^{[10
,12
]}

Wang, Sophia S. ^{[13
]}

Nieters, Alexandra ^{[14
]}

Vijai, Joseph ^{[15
]}

Yeager, Meredith ^{[18
]}

Wang, Zhaoming ^{[18
]}

Ghesquieres, Herve ^{[19
,21
]}

Mckay, James ^{[22
]}

Conde, Lucia ^{[23
,24
,26
]}

de Bakker, Paul I. W. ^{[6
,7
]}

Cox, David G. ^{[20
]}

Burdett, Laurie ^{[18
]}

Monnereau, Alain ^{[27
,28
,29
]}

Flowers, Christopher R. ^{[30
]}

De Roos, Anneclaire J. ^{[31
,32
]}

Brooks-Wilson, Angela R. ^{[11
,33
]}

Giles, Graham G. ^{[34
,35
]}

Melbye, Mads ^{[37
,38
]}

Gu, Jian ^{[39
]}

Jackson, Rebecca D. ^{[40
]}

Kane, Eleanor ^{[41
]}

Purdue, Mark P. ^{[42
]}

Vajdic, Claire M. ^{[43
]}

Albanes, Demetrius ^{[1
]}

Kelly, Rachel S. ^{[44
,47
]}

Zucca, Mariagrazia ^{[49
]}

Bertrand, Kimberly A. ^{[44
,51
,52
]}

Zeleniuch-Jacquotte, Anne ^{[53
,54
,55
]}

Lawrence, Charles ^{[56
]}

Hutchinson, Amy ^{[18
]}

Zhi, Degui ^{[25
]}

Habermann, Thomas M. ^{[3
]}

Link, Brian K. ^{[57
]}

Novak, Anne J. ^{[3
]}

Dogan, Ahmet ^{[16
,17
]}

Asmann, Yan W. ^{[4
]}

Liebow, Mark ^{[3
]}

Thompson, Carrie A. ^{[3
]}

Ansell, Stephen M. ^{[3
]}

Witzig, Thomas E. ^{[3
]}

Tilly, Herve ^{[58
]}

Haioun, Corinne ^{[59
,60
]}

Molina, Thierry J. ^{[61
]}

机构：

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

[2] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[3] Mayo Clin, Dept Med, Rochester, MN USA

[4] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA

[5] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands

[6] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[7] Univ Med Ctr Utrecht, Dept Med Genet & Epidemiol, Utrecht, Netherlands

[8] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[9] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA

[10] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada

[11] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada

[12] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada

[13] City Hope Beckman Res Inst, Div Canc Etiol, Duarte, CA USA

[14] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Baden Wurttembe, Germany

[15] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[16] Mem Sloan Kettering Canc Ctr, Dept Lab Med, 1275 York Ave, New York, NY 10021 USA

[17] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[18] NCI, Div Canc Epidemiol & Genet, Canc Genom Res Lab, Gaithersburg, MD USA

[19] Ctr Leon Berard, Canc Res Ctr Lyon, Dept Hematol, F-69373 Lyon, France

[20] Ctr Leon Berard, Canc Res Ctr Lyon, INSERM U1052, F-69373 Lyon, France

[21] CNRS, UMR5239, Lab Biol Mol Cellule, Pierre Benite, France

[22] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France

[23] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA

[24] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA

[25] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA

[26] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA

[27] Sorbonne Paris Cite, INSERM, Ctr Res Epidemiol & Stat, Epidemiol Childhood & Adolescent Canc Grp, Paris, France

[28] Univ Paris 05, Paris, France

[29] Inst Bergonie, Registre Hemopathies Malignes Gironde, Bordeaux, France

[30] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA

[31] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA

[32] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[33] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada

[34] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

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

[36] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia

[37] Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

[38] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA

[39] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[40] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA

[41] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England

[42] Ontario Hlth Study, Toronto, ON, Canada

[43] Univ New S Wales, Ctr Big Data Res Hlth, Sydney, NSW, Australia

[44] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[45] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[46] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[47] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England

[48] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England

[49] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy

[50] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy

来源：

HUMAN MOLECULAR GENETICS | 2016年 / 25卷 / 08期

基金：

美国国家卫生研究院; 英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; EPIDEMIOLOGIC RESEARCH; SUSCEPTIBILITY LOCI; CLASSIFICATION; DYSFUNCTION; NEOPLASMS; METAANALYSIS; CONSORTIUM; DISEASE; COMMON;

D O I：

10.1093/hmg/ddw027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

引用

页码：1663 / 1676

页数：14

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