Predicted leukocyte telomere length and risk of germ cell tumours
Menée à l'aide d'une méthode de randomisation mendélienne et de données de bases américaines portant sur 1 413 patients pédiatriques atteints d'une tumeur des cellules germinales, 1 220 parents biologiques et 1 022 témoins non apparentés, puis répliquée à l'aide de données de la "UK Biobank" portant sur 1 589 témoins et 396 adultes atteints d'un cancer du testicule, cette étude analyse l'association entre la longueur des télomères des leucocytes et le risque de tumeur des cellules germinales chez l'enfant et l'adulte
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.