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

Mitchell J. Machiela, Qing Lan, Susan L. Slager, Roel C.H. Vermeulen, Lauren R. Teras, Nicola J. Camp, James R. Cerhan, John J. Spinelli, Sophia S. Wang, Alexandra Nieters, Joseph Vijai, Meredith Yeager, Zhaoming Wang, Hervé Ghesquières, James McKay, Lucia Conde, Paul I. W. de Bakker, David G. Cox, Laurie Burdett, Alain Monnereau & 100 others Christopher R. Flowers, Anneclaire J. De Roos, Angela R. Brooks-Wilson, Graham G. Giles, Mads Melbye, Jian Gu, Rebecca D. Jackson, Eleanor Kane, Mark P. Purdue, Claire M. Vajdic, Demetrius Albanes, Rachel S. Kelly, Mariagrazia Zucca, Kimberly A. Bertrand, Anne Zeleniuch-Jacquotte, Charles Lawrence, Amy Hutchinson, Degui Zhi, Thomas M. Habermann, Brian K. Link, Anne J. Novak, Ahmet Dogan, Yan W. Asmann, Mark Liebow, Carrie A. Thompson, Stephen M. Ansell, Thomas E. Witzig, Hervé Tilly, Corinne Haioun, Thierry J. Molina, Henrik Hjalgrim, Bengt Glimelius, Hans Olov Adami, Göran Roos, Paige M. Bracci, Jacques Riby, Martyn T. Smith, Elizabeth A. Holly, Wendy Cozen, Patricia Hartge, Lindsay M. Morton, Richard K. Severson, Lesley F. Tinker, Kari E. North, Nikolaus Becker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, Anthony Staines, Tracy Lightfoot, Simon Crouch, Alex Smith, Eve Roman, W. Ryan Diver, Kenneth Offit, Andrew Zelenetz, Robert J. Klein, Danylo J. Villano, Tongzhang Zheng, Yawei Zhang, Theodore R. Holford, Jenny Turner, Melissa C. Southey, Jacqueline Clavel, Jarmo Virtamo, Stephanie Weinstein, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Heiner Boeing, Anne Tjønneland, Emanuele Angelucci, Simonetta Di Lollo, Marco Rais, Immaculata De Vivo, Edward Giovannucci, Peter Kraft, Jinyan Huang, Baoshan Ma, Yuanqing Ye, Brian C.H. Chiu, Liming Liang, Ju Hyun Park, Charles C. Chung, Dennis D. Weisenburger, Joseph F. Fraumeni, Gilles Salles, Martha Glenn, Lisa Cannon-Albright, Karen Curtin, Xifeng Wu, Karin E. Smedby, Silvia de Sanjose, Christine F. Skibola, Sonja I. Berndt, Brenda M. Birmann, Stephen J. Chanock, Nathaniel Rothman

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 × 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 × 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 lengthmay increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

LanguageEnglish
Pages1663-1676
Number of pages14
JournalHuman molecular genetics
Volume25
Issue number8
DOIs
Publication statusPublished - 15 Apr 2016

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Telomere
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
B-Cell Chronic Lymphocytic Leukemia
B-Lymphocytes
Odds Ratio
Follicular Lymphoma
Environmental Exposure
Causality
Single Nucleotide Polymorphism
Lymphoma
Leukocytes
Alleles
Genotype

Cite this

Machiela, M. J., Lan, Q., Slager, S. L., Vermeulen, R. C. H., Teras, L. R., Camp, N. J., ... Rothman, N. (2016). Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes. Human molecular genetics, 25(8), 1663-1676. https://doi.org/10.1093/hmg/ddw027
Machiela, Mitchell J. ; Lan, Qing ; Slager, Susan L. ; Vermeulen, Roel C.H. ; Teras, Lauren R. ; Camp, Nicola J. ; Cerhan, James R. ; Spinelli, John J. ; Wang, Sophia S. ; Nieters, Alexandra ; Vijai, Joseph ; Yeager, Meredith ; Wang, Zhaoming ; Ghesquières, Hervé ; McKay, James ; Conde, Lucia ; de Bakker, Paul I. W. ; Cox, David G. ; Burdett, Laurie ; Monnereau, Alain ; Flowers, Christopher R. ; De Roos, Anneclaire J. ; Brooks-Wilson, Angela R. ; Giles, Graham G. ; Melbye, Mads ; Gu, Jian ; Jackson, Rebecca D. ; Kane, Eleanor ; Purdue, Mark P. ; Vajdic, Claire M. ; Albanes, Demetrius ; Kelly, Rachel S. ; Zucca, Mariagrazia ; Bertrand, Kimberly A. ; Zeleniuch-Jacquotte, Anne ; Lawrence, Charles ; Hutchinson, Amy ; Zhi, Degui ; Habermann, Thomas M. ; Link, Brian K. ; Novak, Anne J. ; Dogan, Ahmet ; Asmann, Yan W. ; Liebow, Mark ; Thompson, Carrie A. ; Ansell, Stephen M. ; Witzig, Thomas E. ; Tilly, Hervé ; Haioun, Corinne ; Molina, Thierry J. ; Hjalgrim, Henrik ; Glimelius, Bengt ; Adami, Hans Olov ; Roos, Göran ; Bracci, Paige M. ; Riby, Jacques ; Smith, Martyn T. ; Holly, Elizabeth A. ; Cozen, Wendy ; Hartge, Patricia ; Morton, Lindsay M. ; Severson, Richard K. ; Tinker, Lesley F. ; North, Kari E. ; Becker, Nikolaus ; Benavente, Yolanda ; Boffetta, Paolo ; Brennan, Paul ; Foretova, Lenka ; Maynadie, Marc ; Staines, Anthony ; Lightfoot, Tracy ; Crouch, Simon ; Smith, Alex ; Roman, Eve ; Ryan Diver, W. ; Offit, Kenneth ; Zelenetz, Andrew ; Klein, Robert J. ; Villano, Danylo J. ; Zheng, Tongzhang ; Zhang, Yawei ; Holford, Theodore R. ; Turner, Jenny ; Southey, Melissa C. ; Clavel, Jacqueline ; Virtamo, Jarmo ; Weinstein, Stephanie ; Riboli, Elio ; Vineis, Paolo ; Kaaks, Rudolph ; Boeing, Heiner ; Tjønneland, Anne ; Angelucci, Emanuele ; Di Lollo, Simonetta ; Rais, Marco ; De Vivo, Immaculata ; Giovannucci, Edward ; Kraft, Peter ; Huang, Jinyan ; Ma, Baoshan ; Ye, Yuanqing ; Chiu, Brian C.H. ; Liang, Liming ; Park, Ju Hyun ; Chung, Charles C. ; Weisenburger, Dennis D. ; Fraumeni, Joseph F. ; Salles, Gilles ; Glenn, Martha ; Cannon-Albright, Lisa ; Curtin, Karen ; Wu, Xifeng ; Smedby, Karin E. ; de Sanjose, Silvia ; Skibola, Christine F. ; Berndt, Sonja I. ; Birmann, Brenda M. ; Chanock, Stephen J. ; Rothman, Nathaniel. / Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes. In: Human molecular genetics. 2016 ; Vol. 25, No. 8. pp. 1663-1676.
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title = "Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes",
abstract = "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 × 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 × 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 lengthmay increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.",
author = "Machiela, {Mitchell J.} and Qing Lan and Slager, {Susan L.} and Vermeulen, {Roel C.H.} and Teras, {Lauren R.} and Camp, {Nicola J.} and Cerhan, {James R.} and Spinelli, {John J.} and Wang, {Sophia S.} and Alexandra Nieters and Joseph Vijai and Meredith Yeager and Zhaoming Wang and Herv{\'e} Ghesqui{\`e}res and James McKay and Lucia Conde and {de Bakker}, {Paul I. W.} and Cox, {David G.} and Laurie Burdett and Alain Monnereau and Flowers, {Christopher R.} and {De Roos}, {Anneclaire J.} and Brooks-Wilson, {Angela R.} and Giles, {Graham G.} and Mads Melbye and Jian Gu and Jackson, {Rebecca D.} and Eleanor Kane and Purdue, {Mark P.} and Vajdic, {Claire M.} and Demetrius Albanes and Kelly, {Rachel S.} and Mariagrazia Zucca and Bertrand, {Kimberly A.} and Anne Zeleniuch-Jacquotte and Charles Lawrence and Amy Hutchinson and Degui Zhi and Habermann, {Thomas M.} and Link, {Brian K.} and Novak, {Anne J.} and Ahmet Dogan and Asmann, {Yan W.} and Mark Liebow and Thompson, {Carrie A.} and Ansell, {Stephen M.} and Witzig, {Thomas E.} and Herv{\'e} Tilly and Corinne Haioun and Molina, {Thierry J.} and Henrik Hjalgrim and Bengt Glimelius and Adami, {Hans Olov} and G{\"o}ran Roos and Bracci, {Paige M.} and Jacques Riby and Smith, {Martyn T.} and Holly, {Elizabeth A.} and Wendy Cozen and Patricia Hartge and Morton, {Lindsay M.} and Severson, {Richard K.} and Tinker, {Lesley F.} and North, {Kari E.} and Nikolaus Becker and Yolanda Benavente and Paolo Boffetta and Paul Brennan and Lenka Foretova and Marc Maynadie and Anthony Staines and Tracy Lightfoot and Simon Crouch and Alex Smith and Eve Roman and {Ryan Diver}, W. and Kenneth Offit and Andrew Zelenetz and Klein, {Robert J.} and Villano, {Danylo J.} and Tongzhang Zheng and Yawei Zhang and Holford, {Theodore R.} and Jenny Turner and Southey, {Melissa C.} and Jacqueline Clavel and Jarmo Virtamo and Stephanie Weinstein and Elio Riboli and Paolo Vineis and Rudolph Kaaks and Heiner Boeing and Anne Tj{\o}nneland and Emanuele Angelucci and {Di Lollo}, Simonetta and Marco Rais and {De Vivo}, Immaculata and Edward Giovannucci and Peter Kraft and Jinyan Huang and Baoshan Ma and Yuanqing Ye and Chiu, {Brian C.H.} and Liming Liang and Park, {Ju Hyun} and Chung, {Charles C.} and Weisenburger, {Dennis D.} and Fraumeni, {Joseph F.} and Gilles Salles and Martha Glenn and Lisa Cannon-Albright and Karen Curtin and Xifeng Wu and Smedby, {Karin E.} and {de Sanjose}, Silvia and Skibola, {Christine F.} and Berndt, {Sonja I.} and Birmann, {Brenda M.} and Chanock, {Stephen J.} and Nathaniel Rothman",
year = "2016",
month = "4",
day = "15",
doi = "10.1093/hmg/ddw027",
language = "English",
volume = "25",
pages = "1663--1676",
journal = "Human molecular genetics",
issn = "0964-6906",
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}

Machiela, MJ, Lan, Q, Slager, SL, Vermeulen, RCH, Teras, LR, Camp, NJ, Cerhan, JR, Spinelli, JJ, Wang, SS, Nieters, A, Vijai, J, Yeager, M, Wang, Z, Ghesquières, H, McKay, J, Conde, L, de Bakker, PIW, Cox, DG, Burdett, L, Monnereau, A, Flowers, CR, De Roos, AJ, Brooks-Wilson, AR, Giles, GG, Melbye, M, Gu, J, Jackson, RD, Kane, E, Purdue, MP, Vajdic, CM, Albanes, D, Kelly, RS, Zucca, M, Bertrand, KA, Zeleniuch-Jacquotte, A, Lawrence, C, Hutchinson, A, Zhi, D, Habermann, TM, Link, BK, Novak, AJ, Dogan, A, Asmann, YW, Liebow, M, Thompson, CA, Ansell, SM, Witzig, TE, Tilly, H, Haioun, C, Molina, TJ, Hjalgrim, H, Glimelius, B, Adami, HO, Roos, G, Bracci, PM, Riby, J, Smith, MT, Holly, EA, Cozen, W, Hartge, P, Morton, LM, Severson, RK, Tinker, LF, North, KE, Becker, N, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Staines, A, Lightfoot, T, Crouch, S, Smith, A, Roman, E, Ryan Diver, W, Offit, K, Zelenetz, A, Klein, RJ, Villano, DJ, Zheng, T, Zhang, Y, Holford, TR, Turner, J, Southey, MC, Clavel, J, Virtamo, J, Weinstein, S, Riboli, E, Vineis, P, Kaaks, R, Boeing, H, Tjønneland, A, Angelucci, E, Di Lollo, S, Rais, M, De Vivo, I, Giovannucci, E, Kraft, P, Huang, J, Ma, B, Ye, Y, Chiu, BCH, Liang, L, Park, JH, Chung, CC, Weisenburger, DD, Fraumeni, JF, Salles, G, Glenn, M, Cannon-Albright, L, Curtin, K, Wu, X, Smedby, KE, de Sanjose, S, Skibola, CF, Berndt, SI, Birmann, BM, Chanock, SJ & Rothman, N 2016, 'Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes', Human molecular genetics, vol. 25, no. 8, pp. 1663-1676. https://doi.org/10.1093/hmg/ddw027

Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes. / Machiela, Mitchell J.; Lan, Qing; Slager, Susan L.; Vermeulen, Roel C.H.; Teras, Lauren R.; Camp, Nicola J.; Cerhan, James R.; Spinelli, John J.; Wang, Sophia S.; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I. W.; Cox, David G.; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Giles, Graham G.; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Purdue, Mark P.; Vajdic, Claire M.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J.; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Roos, Göran; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Ryan Diver, W.; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C.H.; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Fraumeni, Joseph F.; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E.; de Sanjose, Silvia; Skibola, Christine F.; Berndt, Sonja I.; Birmann, Brenda M.; Chanock, Stephen J.; Rothman, Nathaniel.

In: Human molecular genetics, Vol. 25, No. 8, 15.04.2016, p. 1663-1676.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

AU - Machiela, Mitchell J.

AU - Lan, Qing

AU - Slager, Susan L.

AU - Vermeulen, Roel C.H.

AU - Teras, Lauren R.

AU - Camp, Nicola J.

AU - Cerhan, James R.

AU - Spinelli, John J.

AU - Wang, Sophia S.

AU - Nieters, Alexandra

AU - Vijai, Joseph

AU - Yeager, Meredith

AU - Wang, Zhaoming

AU - Ghesquières, Hervé

AU - McKay, James

AU - Conde, Lucia

AU - de Bakker, Paul I. W.

AU - Cox, David G.

AU - Burdett, Laurie

AU - Monnereau, Alain

AU - Flowers, Christopher R.

AU - De Roos, Anneclaire J.

AU - Brooks-Wilson, Angela R.

AU - Giles, Graham G.

AU - Melbye, Mads

AU - Gu, Jian

AU - Jackson, Rebecca D.

AU - Kane, Eleanor

AU - Purdue, Mark P.

AU - Vajdic, Claire M.

AU - Albanes, Demetrius

AU - Kelly, Rachel S.

AU - Zucca, Mariagrazia

AU - Bertrand, Kimberly A.

AU - Zeleniuch-Jacquotte, Anne

AU - Lawrence, Charles

AU - Hutchinson, Amy

AU - Zhi, Degui

AU - Habermann, Thomas M.

AU - Link, Brian K.

AU - Novak, Anne J.

AU - Dogan, Ahmet

AU - Asmann, Yan W.

AU - Liebow, Mark

AU - Thompson, Carrie A.

AU - Ansell, Stephen M.

AU - Witzig, Thomas E.

AU - Tilly, Hervé

AU - Haioun, Corinne

AU - Molina, Thierry J.

AU - Hjalgrim, Henrik

AU - Glimelius, Bengt

AU - Adami, Hans Olov

AU - Roos, Göran

AU - Bracci, Paige M.

AU - Riby, Jacques

AU - Smith, Martyn T.

AU - Holly, Elizabeth A.

AU - Cozen, Wendy

AU - Hartge, Patricia

AU - Morton, Lindsay M.

AU - Severson, Richard K.

AU - Tinker, Lesley F.

AU - North, Kari E.

AU - Becker, Nikolaus

AU - Benavente, Yolanda

AU - Boffetta, Paolo

AU - Brennan, Paul

AU - Foretova, Lenka

AU - Maynadie, Marc

AU - Staines, Anthony

AU - Lightfoot, Tracy

AU - Crouch, Simon

AU - Smith, Alex

AU - Roman, Eve

AU - Ryan Diver, W.

AU - Offit, Kenneth

AU - Zelenetz, Andrew

AU - Klein, Robert J.

AU - Villano, Danylo J.

AU - Zheng, Tongzhang

AU - Zhang, Yawei

AU - Holford, Theodore R.

AU - Turner, Jenny

AU - Southey, Melissa C.

AU - Clavel, Jacqueline

AU - Virtamo, Jarmo

AU - Weinstein, Stephanie

AU - Riboli, Elio

AU - Vineis, Paolo

AU - Kaaks, Rudolph

AU - Boeing, Heiner

AU - Tjønneland, Anne

AU - Angelucci, Emanuele

AU - Di Lollo, Simonetta

AU - Rais, Marco

AU - De Vivo, Immaculata

AU - Giovannucci, Edward

AU - Kraft, Peter

AU - Huang, Jinyan

AU - Ma, Baoshan

AU - Ye, Yuanqing

AU - Chiu, Brian C.H.

AU - Liang, Liming

AU - Park, Ju Hyun

AU - Chung, Charles C.

AU - Weisenburger, Dennis D.

AU - Fraumeni, Joseph F.

AU - Salles, Gilles

AU - Glenn, Martha

AU - Cannon-Albright, Lisa

AU - Curtin, Karen

AU - Wu, Xifeng

AU - Smedby, Karin E.

AU - de Sanjose, Silvia

AU - Skibola, Christine F.

AU - Berndt, Sonja I.

AU - Birmann, Brenda M.

AU - Chanock, Stephen J.

AU - Rothman, Nathaniel

PY - 2016/4/15

Y1 - 2016/4/15

N2 - 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 × 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 × 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 lengthmay increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

AB - 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 × 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 × 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 lengthmay increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

UR - http://www.scopus.com/inward/record.url?scp=84963721851&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/nhmrc/209057

UR - http://purl.org/au-research/grants/nhmrc/251553

UR - http://purl.org/au-research/grants/nhmrc/504711

UR - http://purl.org/au-research/grants/nhmrc/990920

U2 - 10.1093/hmg/ddw027

DO - 10.1093/hmg/ddw027

M3 - Article

VL - 25

SP - 1663

EP - 1676

JO - Human molecular genetics

T2 - Human molecular genetics

JF - Human molecular genetics

SN - 0964-6906

IS - 8

ER -