Table 1.
TERT locus polymorphisms for which the meta-analysis demonstrated a statistically significant association with cancer risk*
| Polymorphism data | Study features | Meta-analysis findings | ||||||||||
| Polymorphism ID | Gene | Allele | Race or ethnicity† | No. of studies | Case subjects, No. | Control subjects, No. | Cancer type‡ | OR (95% CI) | P for Z test§ | I 2, % | P for Q test§ | Level of evidence║ |
| rs13167280 | TERT | T | White | 2 | 1581 | 1889 | Bladder | 1.23 (1.07 to 1.42) | .004 | 0 | .45 | BAA/moderate |
| rs1801075 | Intergenic | C | Miscellany | 4 | 3552 | 4340 | Lung (miscellany) | 0.88 (0.80 to 0.96) | .006 | 0 | .49 | AAC/weak |
| rs2242652 | TERT | T | White | 4 | 33600 | 32419 | Prostate | 0.82 (0.76 to 0.89) | 9.0E-07¶ | 61 | .05 | ACA/weak |
| rs2735845 | Intergenic | G | Miscellany | 3 | 7213 | 7523 | Lung (miscellany) | 1.11 (1.05 to 1.17) | 2.3E-04¶ | 0 | .39 | AAC/weak |
| rs2736098 | TERT | A | Miscellany | 3 | 4617 | 10134 | Bladder | 1.19 (1.12 to 1.25) | 8.6E-10¶ | 0 | .87 | AAA/strong |
| rs2736098 | TERT | A | Miscellany | 4 | 6949 | 12492 | Lung (miscellany) | 1.21 (1.15 to 1.27) | 2.2E-13¶ | 0 | .99 | AAA/strong |
| rs2736100 | TERT | C | Miscellany | 2 | 970 | 1072 | Bladder | 1.19 (1.05 to 1.34) | .007 | 0 | .64 | BAA/moderate |
| rs2736100 | TERT | C | Miscellany | 6 | 6871 | 12449 | CNS | 1.34 (1.23 to 1.46) | 4.4E-11¶ | 60 | .029 | ACA/weak |
| rs2736100 | TERT | C | White | 5 | 5918 | 11413 | CNS | 1.35 (1.22 to 1.50) | 1.2E-08¶ | 65 | .021 | ACA/weak |
| rs2736100 | TERT | C | Miscellany | 23 | 50917 | 72598 | Lung (miscellany) | 1.19 (1.14 to 1.23) | <1.0E-16¶ | 77 | 2.9E-11 | ACA/weak |
| rs2736100 | TERT | C | White | 11 | 30650 | 41248 | Lung (miscellany) | 1.11 (1.08 to 1.15) | 1.1E-12¶ | 35 | .12 | AAC/weak |
| rs2736100 | TERT | C | Asian | 12 | 20267 | 31350 | Lung (miscellany) | 1.26 (1.20 to 1.32) | <1.0E-16¶ | 68 | 3.5E-04 | ACB/weak |
| rs2736100 | TERT | C | Miscellany | 14 | 22045 | 68197 | Lung (adenocarcinoma) | 1.30 (1.25 to 1.36) | <1.0E-16¶ | 62 | .001 | ACB/weak |
| rs2736100 | TERT | C | Miscellany | 13 | 11645 | 57483 | Lung (squamous) | 1.06 (1.01 to 1.12) | .017 | 54 | .011 | ACC/weak |
| rs2736100 | TERT | C | Miscellany | 29 | 35509 | 61787 | Lung (NSCLC) | 1.19 (1.14 to 1.25) | 3.3E-14¶ | 80 | 1.1E-16 | ACA/weak |
| rs2736100 | TERT | C | White | 6 | 9540 | 37840 | Lung (adenocarcinoma) | 1.22 (1.17 to 1.27) | <1.0E-16¶ | 0 | .42 | AAA/strong |
| rs2736100 | TERT | C | Asian | 8 | 12505 | 30357 | Lung (adenocarcinoma) | 1.35 (1.29 to 1.42) | <1.0E-16¶ | 47 | .06 | ABA/moderate |
| rs2736100 | TERT | C | White | 6 | 6626 | 37840 | Lung (squamous) | 1.05 (1.00 to 1.10) | .043 | 30 | .21 | ABA/moderate |
| rs2736100 | TERT | C | White | 13 | 16572 | 37840 | Lung (NSCLC) | 1.15 (1.09 to 1.22) | 1.2E-06¶ | 73 | 9.2E-06 | ACA/weak |
| rs2736100 | TERT | C | Asian | 16 | 18937 | 23947 | Lung (NSCLC) | 1.24 (1.16 to 1.31) | 2.4E-12¶ | 74 | 5.2E-07 | ACA/weak |
| rs2736100 | TERT | C | White | 2 | 3851 | 3934 | Pancreas | 1.12 (1.04 to 1.20) | .001 | 0 | .77 | AAC/weak |
| rs2736100 | TERT | C | White | 3 | 1959 | 8679 | Testis | 0.75 (0.70 to 0.81) | 4.4E-16¶ | 0 | .62 | AAA/strong |
| rs2853668 | Intergenic | T | White | 2 | 11067 | 12517 | Colon | 0.90 (0.82 to 0.99) | .034 | 72 | .05 | ACC/weak |
| rs2853668 | Intergenic | T | Miscellany | 2 | 5531 | 6284 | Lung (miscellany) | 1.09 (1.02 to 1.15) | .009 | 0 | .66 | AAC/weak |
| rs2853668 | Intergenic | T | White | 2 | 3851 | 3934 | Pancreas | 0.92 (0.85 to 0.99) | .046 | 0 | .68 | AAC/weak |
| rs2853676 | TERT | A | Miscellany | 4 | 6010 | 8313 | CNS | 1.26 (1.21 to 1.32) | <1.0E-16¶ | 0 | .58 | AAA/strong |
| rs2853676 | TERT | A | Miscellany | 3 | 11205 | 11957 | Lung (miscellany) | 1.06 (1.01 to 1.10) | .008 | 0 | .79 | AAC/weak |
| rs31489 | CLPTM1L | A | Miscellany | 6 | 13929 | 16047 | Lung (miscellany) | 0.83 (0.78 to 0.88) | 4.2E-09¶ | 55 | .05 | ACA/weak |
| rs31489 | CLPTM1L | A | White | 4 | 10594 | 11070 | Lung (miscellany) | 0.84 (0.78 to 0.90) | 1.5E-06¶ | 58 | .07 | ACA/weak |
| rs31489 | CLPTM1L | A | Asian | 2 | 3335 | 4977 | Lung (miscellany) | 0.80 (0.70 to 0.91) | .001 | 44 | .18 | ABA/moderate |
| rs31489 | CLPTM1L | A | White | 2 | 3851 | 3934 | Pancreas | 1.18 (1.06 to 1.32) | .003 | 70 | .06 | ACA/weak |
| rs31489 | CLPTM1L | A | White | 2 | 1191 | 5805 | Testis | 1.28 (1.16 to 1.41) | 1.4E-06¶ | 18 | .27 | AAA/strong |
| rs380286 | CLPTM1L | A | Miscellany | 2 | 5529 | 6289 | Lung (miscellany) | 0.85 (0.80 to 0.91) | 5.8E-07¶ | 0 | .84 | AAA/strong |
| rs401681 | CLPTM1L | T | Miscellany | 4 | 8645 | 41188 | Bladder | 0.89 (0.86 to 0.92) | 9.2E-11¶ | 0 | .81 | AAC/weak |
| rs401681 | CLPTM1L | T | White | 3 | 4152 | 32824 | Pancreas | 1.14 (1.01 to 1.29) | .037 | 77 | .013 | ACC/weak |
| rs401681 | CLPTM1L | T | White | 3 | 11235 | 74276 | Prostate | 0.92 (0.89 to 0.95) | 3.8E-06¶ | 0 | .63 | AAC/weak |
| rs401681 | CLPTM1L | T | White | 3 | 3941 | 32808 | BCC (skin) | 0.82 (0.76 to 0.89) | 4.2E-06¶ | 49 | .14 | ABA/moderate |
| rs401681 | CLPTM1L | T | White | 5 | 8012 | 38925 | Melanoma (skin) | 1.12 (1.03 to 1.22) | .006 | 72 | .007 | ACC/weak |
| rs401681 | CLPTM1L | T | White | 3 | 1478 | 30525 | SCC (skin) | 0.92 (0.84 to 0.99) | .046 | 0 | .57 | AAC/weak |
| rs401681 | CLPTM1L | T | Miscellany | 12 | 25674 | 58027 | Lung (miscellany) | 0.87 (0.84 to 0.90) | <1.0E-16¶ | 33 | .13 | ABA/moderate |
| rs401681 | CLPTM1L | T | White | 8 | 18641 | 48866 | Lung (miscellany) | 0.87 (0.84 to 0.90) | 3.5E-14¶ | 34 | .15 | ABA/moderate |
| rs401681 | CLPTM1L | T | Asian | 4 | 7033 | 9161 | Lung (miscellany) | 0.86 (0.81 to 0.93) | 2.9E-05¶ | 46 | .13 | ABA/moderate |
| rs401681 | CLPTM1L | T | Miscellany | 6 | 5900 | 43343 | Lung (adenocarcinoma) | 0.87 (0.81 to 0.93) | 4.3E-05¶ | 52 | .06 | ACA/weak |
| rs401681 | CLPTM1L | T | Miscellany | 5 | 5319 | 40522 | Lung (squamous) | 0.85 (0.76 to 0.96) | .010 | 72 | .006 | ACA/weak |
| rs401681 | CLPTM1L | T | Miscellany | 12 | 11852 | 53575 | Lung (NSCLC) | 0.86 (0.82 to 0.91) | 1.9E-07¶ | 56 | .01 | ACA/weak |
| rs401681 | CLPTM1L | T | White | 3 | 2231 | 37259 | Lung (adenocarcinoma) | 0.90 (0.82 to 0.98) | .019 | 45 | .16 | ABC/weak |
| rs401681 | CLPTM1L | T | Asian | 3 | 3669 | 6084 | Lung (adenocarcinoma) | 0.84 (0.76 to 0.93) | 7.5E-04 | 57 | .10 | ACA/weak |
| rs401681 | CLPTM1L | T | Asian | 2 | 736 | 4184 | Lung (squamous) | 0.85 (0.75 to 0.96) | .010 | 0 | .95 | BAA/moderate |
| rs401681 | CLPTM1L | T | White | 7 | 7447 | 43307 | Lung (NSCLC) | 0.87 (0.80 to 0.95) | .001 | 67 | .01 | ACA/weak |
| rs401681 | CLPTM1L | T | Asian | 5 | 4405 | 10268 | Lung (NSCLC) | 0.84 (0.79 to 0.90) | 1.5E-07¶ | 14 | .32 | AAA/strong |
| rs402710 | CLPTM1L | T | Miscellany | 2 | 974 | 1055 | Bladder | 0.85 (0.75 to 0.98) | .022 | 0 | .36 | BAA/moderate |
| rs402710 | CLPTM1L | T | Miscellany | 12 | 31364 | 35462 | Lung (miscellany) | 0.88 (0.83 to 0.92) | 8.1E-07¶ | 65 | .002 | ACC/weak |
| rs402710 | CLPTM1L | T | White | 8 | 24471 | 26161 | Lung (miscellany) | 0.89 (0.84 to 0.94) | 5.2E-05¶ | 69 | .004 | ACC/weak |
| rs402710 | CLPTM1L | T | Asian | 4 | 6893 | 9301 | Lung (miscellany) | 0.87 (0.82 to 0.91) | 8.2E-08¶ | 9 | .35 | AAA/strong |
| rs402710 | CLPTM1L | T | Miscellany | 3 | 4929 | 15011 | Lung (adenocarcinoma) | 0.84 (0.80 to 0.89) | 5.9E-10¶ | 0 | .42 | AAA/strong |
| rs402710 | CLPTM1L | T | Miscellany | 3 | 2461 | 15011 | Lung (squamous) | 0.83 (0.77 to 0.89) | 4.1E-07¶ | 0 | .94 | AAA/strong |
| rs402710 | CLPTM1L | T | Miscellany | 8 | 8945 | 31783 | Lung (NSCLC) | 0.84 (0.81 to 0.88) | 2.2E-16¶ | 0 | .78 | AAA/strong |
| rs4246742 | TERT | T | Miscellany | 2 | 5528 | 6274 | Lung (miscellany) | 1.08 (1.01 to 1.15) | .018 | 0 | .83 | AAC/weak |
| rs451360 | CLPTM1L | A | Miscellany | 3 | 6983 | 8058 | Lung (miscellany) | 0.80 (0.70 to 0.92) | .001 | 70 | .035 | ACB/weak |
| rs451360 | CLPTM1L | A | White | 2 | 4652 | 4981 | Lung (miscellany) | 0.85 (0.76 to 0.95) | .004 | 48 | .16 | ABA/moderate |
| rs452384 | CLPTM1L | C | Miscellany | 2 | 5302 | 6823 | Lung (miscellany) | 0.82 (0.74 to 0.90) | 7.4E-05¶ | 52 | .15 | ACA/weak |
| rs452932 | CLPTM1L | C | Miscellany | 2 | 5302 | 6823 | Lung (miscellany) | 0.82 (0.74 to 0.90) | 7.4E-05¶ | 52 | .15 | ACA/weak |
| rs4635969 | Intergenic | A | Miscellany | 4 | 12893 | 13126 | Lung (miscellany) | 0.86 (0.82 to 0.90) | 8.1E-10¶ | 8 | .35 | AAA/strong |
| rs4635969 | Intergenic | A | Miscellany | 2 | 3674 | 8230 | Lung (adenocarcinoma) | 0.81 (0.75 to 0.88) | 1.2E-06¶ | 0 | .87 | AAA/strong |
| rs4635969 | Intergenic | A | Miscellany | 2 | 1594 | 8230 | Lung (squamous) | 0.87 (0.78 to 0.97) | .010 | 0 | .45 | AAA/strong |
| rs4635969 | Intergenic | A | Miscellany | 4 | 5268 | 8230 | Lung (NSCLC) | 0.83 (0.78 to 0.89) | 6.0E-08¶ | 0 | .69 | AAA/strong |
| rs4635969 | Intergenic | A | White | 2 | 3851 | 3934 | Pancreas | 1.22 (1.14 to 1.32) | 1.1E-07¶ | 0 | .86 | AAA/strong |
| rs4635969 | Intergenic | A | White | 3 | 1729 | 9079 | Testis | 1.61 (1.47 to 1.75) | <1.0E-16¶ | 0 | .77 | AAA/strong |
| rs465498 | CLPTM1L | G | Miscellany | 4 | 11579 | 13190 | Lung (miscellany) | 0.79 (0.74 to 0.84) | 2.6E-12¶ | 49 | .12 | ABA/moderate |
| rs465498 | CLPTM1L | G | Asian | 3 | 8608 | 9444 | Lung (miscellany) | 0.76 (0.72 to 0.81) | <1.0E-16¶ | 0 | .76 | AAA/strong |
| rs467095 | CLPTM1L | C | Miscellany | 3 | 7739 | 9271 | Lung (miscellany) | 0.83 (0.78 to 0.87) | 3.9E-11¶ | 0 | .37 | AAA/strong |
| rs4975615 | Intergenic | G | Miscellany | 3 | 6983 | 8058 | Lung (miscellany) | 0.81 (0.76 to 0.87) | 2.7E-10¶ | 26 | .26 | ABA/moderate |
| rs4975616 | Intergenic | G | Miscellany | 7 | 12743 | 14130 | Lung (miscellany) | 0.83 (0.79 to 0.88) | 1.1E-11¶ | 41 | .12 | ABA/moderate |
| rs4975616 | Intergenic | G | White | 2 | 3851 | 3934 | Pancreas | 0.85 (0.78 to 0.94) | .001 | 57 | .13 | ACA/weak |
| rs4975616 | Intergenic | G | White | 2 | 1328 | 5861 | Testis | 1.20 (1.03 to 1.40) | .016 | 55 | .13 | ACA/weak |
| MNS16a | TERT | S | White | 2 | 1764 | 1664 | CNS | 1.19 (1.07 to 1.33) | .001 | 8 | .30 | AAA/strong |
*
Telomerase reverse transcriptase (TERT) locus includes TERT and cleft lip and palate transmembrane 1-like (CLPTM1L) genes. BCC = basal cell carcinoma; CI = confidence interval; CNS =central nervous system; ID = identification; OR = odds ratio; NSCLC = non–small cell lung cancer; SCC =squamous cell carcinoma; SCLC = small cell lung cancer.
†
Miscellany indicates a mix of different races.
‡
Lung (miscellany) indicates a mix of different histological subtypes.
§
All P values calculated by Z test or Q test were two-sided.
║
A, B, and C represent the Venice criteria grades for amount of evidence, replication of association and protection from bias, which ultimately define the level of cumulative evidence (strong, moderate, weak).
¶
Statistically significant P values after Bonferroni adjustment for multiple testing.