Genetically Inferred Telomere Length and Testicular Germ Cell Tumor Risk

Derek W Brown, Qing Lan, Nathaniel Rothman, John Pluta, Kristian Almstrup, Marlene D Dalgaard, Mark H Greene, Tom Grotmol, Chey Loveday, Stephen M Schwartz, Clare Turnbull, Fredrik Wiklund, Peter A Kanetsky, Katherine L Nathanson, Katherine A McGlynn, Mitchell J Machiela, Testicular Cancer Consortium


BACKGROUND: Studies evaluating the association between peripheral blood leukocyte telomere length (LTL) and testicular germ cell tumor (TGCT) risk have produced conflicting results.

METHODS: Using available genotype data from the Testicular Cancer Consortium (TECAC), polygenic risk score and Mendelian randomization analyses of genetic variants previously associated with LTL were used to assess potential etiologic associations between telomere length and TGCT risk.

RESULTS: Genetically inferred telomere length was not associated with TGCT risk among 2,049 cases and 6,921 controls with individual-level genotype data (OR, 1.02; 95% confidence interval, 0.97-1.07). Mendelian randomization analyses using summary statistic data further indicated no evidence for an association between telomere length and TGCT risk among all available TECAC participants (3,558 cases and 13,971 controls).

CONCLUSIONS: Our analyses in the largest molecular genetic testicular cancer study to date provide no evidence for an association between genetically inferred peripheral blood LTL and TGCT risk.

IMPACT: The lack of evidence for an overall association indicates that peripheral blood LTL is likely not a strong biomarker for TGCT risk.


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