Predicted leukocyte telomere length and risk of germ cell tumours.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
06
05
2021
accepted:
17
03
2022
revised:
04
03
2022
pubmed:
4
4
2022
medline:
22
7
2022
entrez:
3
4
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35368045
doi: 10.1038/s41416-022-01798-3
pii: 10.1038/s41416-022-01798-3
pmc: PMC9296514
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
301-312Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA151284
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180899
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180886
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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