Table 2.
Individual effect of leukocyte telomere length (LTL)-related variants on germ cell tumour risk (GCT).
| Paediatric GCT | UKB TGCT | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TDT (N = 610) | Case–control analysisa (N = 803) | Meta-analysis (N = 1413) | Case–Control (N = 396) | |||||||||
| SNP | Chr | Gene | Lb allele | Sc allele | ORd (95% CI) | P value | ORd (95% CI) | P value | ORd (95% CI) | P value | ORd (95% CI) | P value |
| Codd et al. [27] – 7 genetic variants predict LTL | ||||||||||||
| rs11125529 | 2 | ACYP2 | A | C | 1.02 (0.81, 1.30) | 0.855 | 1.02 (0.83, 1.26) | 0.853 | 1.02 (0.87, 1.19) | 0.793 | 0.92 (0.72, 1.17) | 0.480 |
| rs10936599 | 3 | TERC | C | T | 1.12 (0.93, 1.34) | 0.234 | 1.17 (1.01, 1.36) | 0.041 | 1.15 (1.02, 1.29) | 0.018 | 1.10 (0.92, 1.32) | 0.315 |
| rs7675998 | 4 | NAF1 | G | A | 1.24 (1.02, 1.52) | 0.033 | 0.94 (0.79, 1.12) | 0.485 | 1.06 (0.93, 1.20) | 0.399 | 1.17 (0.96, 1.42) | 0.118 |
| rs2736100e | 5 | TERT | C | A | 0.88 (0.75, 1.03) | 0.112 | 0.77 (0.67, 0.89) | 0.0004 | 0.82 (0.74, 0.91) | 0.0003 | 0.83 (0.71, 0.97) | 0.020 |
| rs9420907 | 10 | OBFC1 | C | A | 0.89 (0.72, 1.11) | 0.313 | 1.05 (0.85, 1.29) | 0.645 | 0.97 (0.83, 1.13) | 0.665 | 0.80 (0.63, 1.02) | 0.073 |
| rs8105767f | 19 | ZNF208 | G | A | 1.05 (0.89, 1.25) | 0.544 | 1.02 (0.88, 1.18) | 0.804 | 1.03 (0.92, 1.15) | 0.580 | 1.03 (0.87, 1.22) | 0.715 |
| rs755017 | 20 | RTEL1 | G | A | 1.12 (0.89, 1.42) | 0.337 | 1.06 (0.89, 1.26) | 0.508 | 1.08 (0.94, 1.25) | 0.270 | 0.93 (0.74, 1.18) | 0.560 |
| Li et al. [32] – 20 genetic variants predict LTL | ||||||||||||
| rs3219104 | 1 | PARP1 | C | A | 0.94 (0.77, 1.15) | 0.575 | 0.82 (0.70, 0.96) | 0.015 | 0.87 (0.76, 0.98) | 0.024 | 0.94 (0.76, 1.16) | 0.570 |
| rs55749605 | 3 | SENP7 | C | A | 1.10 (0.92, 1.30) | 0.294 | 1.03 (0.88, 1.20) | 0.716 | 1.06 (0.94, 1.19) | 0.331 | 0.90 (0.76, 1.05) | 0.183 |
| rs10936600 | 3 | TERC | A | T | 1.11 (0.92, 1.32) | 0.272 | 1.18 (1.01, 1.37) | 0.036 | 1.15 (1.02, 1.29) | 0.021 | 0.90 (0.75, 1.09) | 0.282 |
| rs13137667 | 4 | MOB1B | C | T | 1.18 (0.77, 1.82) | 0.442 | 0.75 (0.52, 1.09) | 0.131 | 0.91 (0.69, 1.21) | 0.515 | 0.90 (0.53, 1.52) | 0.683 |
| rs4691895 | 4 | NAF1 | C | G | 1.23 (1.01, 1.50) | 0.037 | 0.89 (0.75, 1.05) | 0.155 | 1.02 (0.90, 1.15) | 0.806 | 1.12 (0.92, 1.35) | 0.263 |
| rs7705526e | 5 | TERT | A | C | 0.81 (0.64, 1.03) | 0.086 | 0.86 (0.72, 1.02) | 0.077 | 0.84 (0.73, 0.97) | 0.015 | 0.82 (0.69, 0.97) | 0.024 |
| rs2853677e | 5 | TERT | G | A | 0.85 (0.70, 1.03) | 0.105 | 0.77 (0.66, 0.90) | 0.001 | 0.80 (0.71, 0.91) | <0.001 | 0.80 (0.68, 0.94) | 0.007 |
| rs34991172 | 6 | CARMIL1 | T | G | 0.66 (0.44, 0.99) | 0.041 | 0.95 (0.63, 1.44) | 0.826 | 0.79 (0.59, 1.06) | 0.111 | 1.16 (0.83, 1.61) | 0.384 |
| rs2736176 | 6 | PRRC2A | C | G | 0.89 (0.74, 1.06) | 0.179 | 0.92 (0.79, 1.07) | 0.256 | 0.90 (0.81, 1.01) | 0.082 | 1.08 (0.91, 1.28) | 0.386 |
| rs59294613 | 7 | POT1 | C | A | 1.00 (0.84, 1.21) | 0.963 | 1.20 (1.02, 1.42) | 0.028 | 1.11 (0.98, 1.25) | 0.096 | 0.93 (0.78, 1.11) | 0.411 |
| rs9419958 | 10 | STN1 (OBFC1) | T | C | 0.90 (0.72, 1.12) | 0.340 | 1.06 (0.86, 1.31) | 0.571 | 0.98 (0.84, 1.14) | 0.809 | 1.24 (0.97, 1.57) | 0.082 |
| rs228595 | 11 | ATM | G | A | 0.91 (0.77, 1.06) | 0.232 | 0.96 (0.83, 1.10) | 0.522 | 0.93 (0.84, 1.04) | 0.206 | 0.89 (0.76, 1.04) | 0.149 |
| rs2302588 | 14 | DCAF4 | C | G | 1.09 (0.83, 1.43) | 0.534 | 1.20 (0.94, 1.52) | 0.138 | 1.15 (0.96, 1.38) | 0.127 | 0.89 (0.69, 1.15) | 0.382 |
| rs3785074 | 16 | TERF2 | G | A | 0.92 (0.77, 1.11) | 0.400 | 0.93 (0.79, 1.10) | 0.402 | 0.93 (0.82, 1.05) | 0.235 | 0.76 (0.64, 0.92) | 0.004 |
| rs62053580 | 16 | RFWD3 | A | G | 0.97 (0.76, 1.26) | 0.846 | 1.14 (0.92, 1.41) | 0.243 | 1.07 (0.91, 1.26) | 0.442 | 0.93 (0.75, 1.16) | 0.530 |
| rs7194734 | 16 | MPHOSPH6 | C | T | 0.79 (0.65, 0.96) | 0.018 | 0.95 (0.79, 1.13) | 0.548 | 0.87 (0.76, 1.00) | 0.043 | 0.97 (0.81, 1.16) | 0.706 |
| rs8105767f | 19 | ZNF208 | G | A | 1.05 (0.89, 1.25) | 0.544 | 1.02 (0.88, 1.18) | 0.804 | 1.03 (0.93, 1.15) | 0.560 | 1.03 (0.87, 1.22) | 0.715 |
| rs75691080 | 20 | RTEL1/STMN3 | C | T | 1.04 (0.76, 1.41) | 0.814 | 1.07 (0.80, 1.44) | 0.639 | 1.06 (0.85, 1.30) | 0.616 | 1.31 (1.00, 1.70) | 0.046 |
| rs34978822 | 20 | RTEL1 | C | G | 2.00 (0.90, 4.45) | 0.083 | 0.92 (0.46, 1.84) | 0.825 | 1.28 (0.76, 2.16) | 0.348 | 1.30 (0.78, 2.16) | 0.315 |
| rs73624724 | 20 | RTEL1/ZBTB46 | C | T | 1.10 (0.87, 1.39) | 0.431 | 1.05 (0.88, 1.25) | 0.611 | 1.07 (0.92, 1.23) | 0.379 | 0.97 (0.77, 1.21) | 0.775 |
TDT transmission disequilibrium test.
aModel adjusted for ancestry-specific PCs (2 PCs for European Ancestry, 3 PCs for Hispanic and Asian Ancestry and 4 PCs for African Ancestry), sex (male and female) and study site (COG, Michigan or California).
bL allele--allele associated with longer leukocyte telomere length.
cS allele--allele associated with shorter telomere length.
dOR and 95% confidence intervals--the odds ratio for the association between lengthening allele and GCT risk.
eTERT SNP evaluated separately due to reported association with testicular GCT.
fSNP appears in both Codd et al. [27] and Li et al. [32] genetic instruments.