Predicted leukocyte telomere length and risk of germ cell tumours

Shannon S Cigan; John J. Meredith; Ava C Kelley; Tianzhong Yang; Erica K. Langer; Anthony J. Hooten; John A Lane; Benjamin R Cole; Mark Krailo; A. Lindsay Frazier; Nathan D Pankratz; Jen Poynter

doi:10.1038/s41416-022-01798-3

Predicted leukocyte telomere length and risk of germ cell tumours

Shannon S Cigan, John J. Meredith, Ava C Kelley, Tianzhong Yang, Erica K. Langer, Anthony J. Hooten, John A Lane, Benjamin R Cole, Mark Krailo, A. Lindsay Frazier, Nathan D Pankratz, Jen Poynter

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Genetically predicted leukocyte telomere length (LTL) has been evaluated in several studies of childhood and adult cancer. We test whether genetically predicted longer LTL is associated with germ cell tumours (GCT) in children and adults. Methods: Paediatric GCT samples were obtained from a Children’s Oncology Group study and state biobank programs in California and Michigan (N = 1413 cases, 1220 biological parents and 1022 unrelated controls). Replication analysis included 396 adult testicular GCTs (TGCT) and 1589 matched controls from the UK Biobank. Mendelian randomisation was used to look at the association between genetically predicted LTL and GCTs and TERT variants were evaluated within GCT subgroups. Results: We identified significant associations between TERT variants reported in previous adult TGCT GWAS in paediatric GCT: TERT/rs2736100-C (OR = 0.82; P = 0.0003), TERT/rs2853677-G (OR = 0.80; P = 0.001), and TERT/rs7705526-A (OR = 0.81; P = 0.003). We also extended these findings to females and tumours outside the testes. In contrast, we did not observe strong evidence for an association between genetically predicted LTL by other variants and GCT risk in children or adults. Conclusion: While TERT is a known susceptibility locus for GCT, our results suggest that LTL predicted by other variants is not strongly associated with risk in either children or adults.

Original language	English (US)
Pages (from-to)	301-312
Number of pages	12
Journal	British Journal of Cancer
Volume	127
Issue number	2
DOIs	https://doi.org/10.1038/s41416-022-01798-3
State	Published - Jul 20 2022

Bibliographical note

Funding Information:
The authors would like to acknowledge the University of Minnesota Genomics Center for performing the genotyping assays and the University of Minnesota Supercomputing Institute for providing hardware and support for the statistical analyses.

Funding Information:
This work was supported by the National Institutes of Health (grant R01 CA151284 to Jenny N. Poynter, National Clinical Trials Network Operations Center grant U10CA180886, and National Clinical Trials Network Statistics and Data Management Center grant U10CA180899), and Epidemiology Award from Alex’s Lemonade Stand Foundation (Wynnewood, Pennsylvania), and the Children’s Cancer Research Fund (Minneapolis, Minnesota).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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title = "Predicted leukocyte telomere length and risk of germ cell tumours",

abstract = "Background: Genetically predicted leukocyte telomere length (LTL) has been evaluated in several studies of childhood and adult cancer. We test whether genetically predicted longer LTL is associated with germ cell tumours (GCT) in children and adults. Methods: Paediatric GCT samples were obtained from a Children{\textquoteright}s Oncology Group study and state biobank programs in California and Michigan (N = 1413 cases, 1220 biological parents and 1022 unrelated controls). Replication analysis included 396 adult testicular GCTs (TGCT) and 1589 matched controls from the UK Biobank. Mendelian randomisation was used to look at the association between genetically predicted LTL and GCTs and TERT variants were evaluated within GCT subgroups. Results: We identified significant associations between TERT variants reported in previous adult TGCT GWAS in paediatric GCT: TERT/rs2736100-C (OR = 0.82; P = 0.0003), TERT/rs2853677-G (OR = 0.80; P = 0.001), and TERT/rs7705526-A (OR = 0.81; P = 0.003). We also extended these findings to females and tumours outside the testes. In contrast, we did not observe strong evidence for an association between genetically predicted LTL by other variants and GCT risk in children or adults. Conclusion: While TERT is a known susceptibility locus for GCT, our results suggest that LTL predicted by other variants is not strongly associated with risk in either children or adults.",

author = "Cigan, {Shannon S} and Meredith, {John J.} and Kelley, {Ava C} and Tianzhong Yang and Langer, {Erica K.} and Hooten, {Anthony J.} and Lane, {John A} and Cole, {Benjamin R} and Mark Krailo and Frazier, {A. Lindsay} and Pankratz, {Nathan D} and Jen Poynter",

note = "Funding Information: The authors would like to acknowledge the University of Minnesota Genomics Center for performing the genotyping assays and the University of Minnesota Supercomputing Institute for providing hardware and support for the statistical analyses. Funding Information: This work was supported by the National Institutes of Health (grant R01 CA151284 to Jenny N. Poynter, National Clinical Trials Network Operations Center grant U10CA180886, and National Clinical Trials Network Statistics and Data Management Center grant U10CA180899), and Epidemiology Award from Alex{\textquoteright}s Lemonade Stand Foundation (Wynnewood, Pennsylvania), and the Children{\textquoteright}s Cancer Research Fund (Minneapolis, Minnesota). Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

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doi = "10.1038/s41416-022-01798-3",

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T1 - Predicted leukocyte telomere length and risk of germ cell tumours

AU - Cigan, Shannon S

AU - Meredith, John J.

AU - Kelley, Ava C

AU - Yang, Tianzhong

AU - Langer, Erica K.

AU - Hooten, Anthony J.

AU - Lane, John A

AU - Cole, Benjamin R

AU - Krailo, Mark

AU - Frazier, A. Lindsay

AU - Pankratz, Nathan D

AU - Poynter, Jen

N1 - Funding Information: The authors would like to acknowledge the University of Minnesota Genomics Center for performing the genotyping assays and the University of Minnesota Supercomputing Institute for providing hardware and support for the statistical analyses. Funding Information: This work was supported by the National Institutes of Health (grant R01 CA151284 to Jenny N. Poynter, National Clinical Trials Network Operations Center grant U10CA180886, and National Clinical Trials Network Statistics and Data Management Center grant U10CA180899), and Epidemiology Award from Alex’s Lemonade Stand Foundation (Wynnewood, Pennsylvania), and the Children’s Cancer Research Fund (Minneapolis, Minnesota). Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2022/7/20

Y1 - 2022/7/20

N2 - Background: Genetically predicted leukocyte telomere length (LTL) has been evaluated in several studies of childhood and adult cancer. We test whether genetically predicted longer LTL is associated with germ cell tumours (GCT) in children and adults. Methods: Paediatric GCT samples were obtained from a Children’s Oncology Group study and state biobank programs in California and Michigan (N = 1413 cases, 1220 biological parents and 1022 unrelated controls). Replication analysis included 396 adult testicular GCTs (TGCT) and 1589 matched controls from the UK Biobank. Mendelian randomisation was used to look at the association between genetically predicted LTL and GCTs and TERT variants were evaluated within GCT subgroups. Results: We identified significant associations between TERT variants reported in previous adult TGCT GWAS in paediatric GCT: TERT/rs2736100-C (OR = 0.82; P = 0.0003), TERT/rs2853677-G (OR = 0.80; P = 0.001), and TERT/rs7705526-A (OR = 0.81; P = 0.003). We also extended these findings to females and tumours outside the testes. In contrast, we did not observe strong evidence for an association between genetically predicted LTL by other variants and GCT risk in children or adults. Conclusion: While TERT is a known susceptibility locus for GCT, our results suggest that LTL predicted by other variants is not strongly associated with risk in either children or adults.

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Predicted leukocyte telomere length and risk of germ cell tumours

Abstract

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