Supplemental Table 1 Telomere pathway genes evaluated in the current study Gene (alias) Name Gene ID Chromosome Functions * ** Binding to the telomerase catalytic subunit hTERT, and inhibiting telomerase activity. Functions as a potent telomerase inhibitor and a PINX1 interacting protein 1 54984 8p23 putative tumor suppressor. Encoding a nuclear protein involved in the telomere maintenance system. Functions by regulating telomere length and protecting Protection of telomeres 1 chromosome ends from illegitimate recombination, catastrophic POT1 homolog 25913 7q31.33 chromosome instability, and abnormal chromosome segregation. Interacting with Rad6, an enzyme required for post-replication repair RAD18 RAD18 homolog 56852 3p25-p24 of damaged DNA, through a conserved ring-finger motif. As an RNA component of telomerase, it serves as a template for the TERC telomerase RNA component 7012 3q26 telomere repeat, and plays a role in maintaining telomere ends. telomeric repeat binding ^ Interacting with TERF2 at the telomere and causing elongation of TERF2IP (RAP1) factor 2, interacting protein 54386 16q23.1 telomeric DNA Encoding a protein component with reverse transcriptase activity, telomerase reverse and playing a role in cellular senescence by regulation of telomerase TERT transcriptase 7015 5p15.33 activity. tankyrase, TRF1-interacting ankyrin-related ADP-ribose With PARP activity, it can modify TERF1, and contribute to the TNKS polymerase 8658 8p23.1 regulation of telomere length. Encoding a telomere specific protein -- a component of the telomere telomeric repeat binding nucleoprotein complex, functions as an inhibitor of telomerase, TRF1 (TERF1) factor (NIMA-interacting) 1 7013 8q13.3 acting in cis to limit the elongation of individual chromosome ends. Encoding a component of the telomere nucleoprotein complex and telomeric repeat binding being a second negative regulator of telomere length, it plays a key TRF2 (TERF2) factor 2 7014 16q22.1 role in the protective activity of telomeres. * As defined in Entrez gene ** Akiyama Y. et al. Oncol Rep 2004, 11:871-4 ^ Li B. and de Lange T. Mol Biol Cell 2003, 14:5060-8; Li B. Oestreich S. and de Lange T. Cell 2000, 101:471-83 Supplemental Table 2 Overall effect of single SNP in telomere pathway genes on breast cancer risk (dominant model), Long Island Breast Cancer Study Project, 1996-1997 SNP500Cancer rs # SNPs Genotype Cases Controls OR (95%CI) * p-value ID PINX1-03 rs12375394 G/A GG 610 (61.9) 683 (64.6) 1.00 (ref) GA 340 (34.5) 327 (30.9) 1.2 (0.9-1.4) 0.14 AA 36 (3.6) 47 (4.5) 0.8 (0.5-1.3) 0.46 GA/AA 376 (38.1) 374 (35.4) 1.11 (0.93-1.33) 0.25 PINX1-04 rs13269447 A/G AA 673 (68.5) 729 (69.4) 1.00 (ref) AG 276 (28.1) 293 (27.9) 1.0 (0.8-1.2) 0.85 GG 33 (3.4) 28 (2.7) 1.3 (0.8-2.2) 0.27 AG/GG 309 (31.5) 321 (30.6) 1.04 (0.87-1.26) 0.64 PINX1-06 rs2271357 C/T CC 336 (33.5) 364 (33.7) 1.00 (ref) CT 493 (49.2) 530 (49.1) 1.0 (0.8-1.2) 0.96 TT 173 (17.3) 185 (17.2) 1.0 (0.8-1.4) 0.72 CT/TT 666 (66.5) 715 (66.3) 1.02 (0.85-1.22) 0.87 PINX1-08 rs6601523 T/C TT 386 (39.3) 397 (37.6) 1.00 (ref) TC 455 (46.3) 491 (46.5) 0.9 (0.8-1.1) 0.54 CC 141 (14.4) 168 (15.9) 0.8 (0.7-1.1) 0.22 TC/CC 596 (60.7) 659 (62.4) 0.92 (0.77-1.10) 0.34 PINX1-13 rs1078543 A/T AA 697 (70.2) 764 (71.7) 1.00 (ref) AT 271 (27.3) 270 (25.3) 1.1 (0.9-1.3) 0.35 TT 25 (2.5) 32 (3.0) 0.9 (0.5-1.5) 0.66 AT/TT 296 (29.8) 302 (28.3) 1.08 (0.89-1.30) 0.45 PINX1-17 rs718742 A/C AA 396 (40.9) 436 (42.0) 1.00 (ref) AC 483 (49.9) 510 (49.1) 1.0 (0.9-1.3) 0.65 CC 89 (9.2) 92 (8.9) 1.1 (0.8-1.5) 0.59 AC/CC 572 (59.1) 602 (58.0) 1.05 (0.88-1.26) 0.58 PINX1-18 rs891554 G/C GG 551 (54.7) 569 (53.1) 1.00 (ref) GC 387 (38.5) 427 (39.8) 1.0 (0.8-1.1) 0.59 CC 68 (6.8) 76 (7.1) 1.0 (0.7-1.4) 0.79 GC/CC 455 (45.2) 503 (46.9) 0.95 (0.80-1.13) 0.57 PINX1-19 rs2271355 A/G AA 337 (34.6) 340 (32.7) 1.00 (ref) AG 465 (47.7) 518 (49.9) 0.9 (0.7-1.1) 0.33 GG 172 (17.7) 181 (17.4) 0.9 (0.7-1.2) 0.68 AG/GG 637 (65.4) 699 (67.3) 0.92 (0.76-1.10) 0.36 PINX1-25 rs6991499 A/G AA 327 (33.2) 355 (33.7) 1.00 (ref) AG 480 (48.8) 507 (48.2) 1.0 (0.8-1.2) 0.83 GG 177 (18.0) 191 (18.1) 1.0 (0.8-1.3) 0.83 AG/GG 657 (66.8) 698 (66.3) 1.02 (0.85-1.23) 0.80 PINX1-26 rs6991526 A/G AA 312 (32.7) 337 (33.4) 1.00 (ref) AG 469 (49.1) 498 (49.3) 1.0 (0.8-1.2) 0.92 GG 174 (18.2) 175 (17.3) 1.1 (0.8-1.4) 0.49 AG/GG 643 (67.3) 673 (66.6) 1.03 (0.86-1.25) 0.73 PINX1-27 rs7004998 C/A CC 396 (39.8) 420 (39.4) 1.00 (ref) CA 463 (46.5) 503 (47.1) 1.0 (0.8-1.2) 0.84 AA 136 (13.7) 144 (13.5) 1.0 (0.8-1.4) 0.85 CA/AA 599 (60.2) 647 (60.6) 0.99 (0.83-1.18) 0.92 PINX1-28 rs11250078 T/C TT 396 (40.2) 417 (39.6) 1.00 (ref) TC 468 (47.5) 483 (45.8) 1.0 (0.8-1.2) 0.95 CC 121 (12.3) 154 (14.6) 0.8 (0.6-1.1) 0.14 TC/CC 589 (59.8) 637 (60.4) 0.96 (0.80-1.15) 0.65 PINX1-33 rs2277130 C/G CC 391 (40.6) 401 (38.8) 1.00 (ref) CG 447 (46.4) 477 (46.1) 1.0 (0.8-1.1) 0.60 GG 125 (13.0) 156 (15.1) 0.8 (0.6-1.1) 0.15 CG/GG 572 (59.4) 633 (61.2) 0.92 (0.77-1.10) 0.34 PINX1-53 rs6601524 C/A CC 579 (58.0) 612 (57.2) 1.00 (ref) CA 355 (35.6) 395 (37.0) 1.0 (0.8-1.2) 0.73 AA 64 (6.4) 62 (5.8) 1.1 (0.8-1.6) 0.54 CA/AA 419 (42.0) 457 (42.8) 0.99 (0.83-1.18) 0.90 PINX1-54 rs2116095 C/T CC 391 (40.6) 391 (38.2) 1.00 (ref) CT 442 (45.9) 464 (45.3) 0.9 (0.8-1.1) 0.54 TT 130 (13.5) 169 (16.5) 0.8 (0.6-0.9) 0.04 CT/TT 572 (59.4) 633 (61.8) 0.89 (0.75-1.07) 0.22 PINX1-55 rs6601525 C/T CC 301 (30.2) 323 (30.3) 1.00 (ref) CT 461 (46.2) 516 (48.3) 1.0 (0.8-1.2) 0.73 TT 235 (23.6) 228 (21.4) 1.1 (0.9-1.4) 0.40 CT/TT 696 (69.8) 744 (69.7) 1.01 (0.84-1.22) 0.92 PINX1-63 rs718741 A/G AA 407 (40.3) 425 (39.5) 1.00 (ref) AG 473 (46.9) 484 (44.9) 1.0 (0.8-1.2) 0.93 GG 129 (12.8) 168 (15.6) 0.8 (0.6-1.0) 0.08 AG/GG 602 (59.7) 652 (60.5) 0.95 (0.80-1.14) 0.58 PINX1-67 rs891555 A/G AA 545 (54.7) 561 (52.8) 1.00 (ref) AG 382 (38.4) 424 (39.9) 0.9 (0.8-1.1) 0.52 GG 69 (6.9) 78 (7.3) 0.9 (0.7-1.3) 0.75 AG/GG 451 (45.3) 502 (47.2) 0.94 (0.79-1.12) 0.51 PINX1-74 rs11250082 G/A GG 641 (64.9) 665 (62.5) 1.00 (ref) GA 304 (30.8) 345 (32.4) 0.9 (0.8-1.1) 0.39 AA 43 (4.3) 54 (5.1) 0.8 (0.5-1.3) 0.39 GA/AA 347 (35.1) 399 (37.5) 0.91 (0.76-1.09) 0.30 POT1-02 rs727506 T/C TT 338 (34.4) 395 (37.5) 1.00 (ref) TC 504 (51.3) 529 (50.3) 1.1 (0.9-1.3) 0.27 CC 141 (14.3) 128 (12.2) 1.3 (0.9-1.7) 0.06 TC/CC 645 (65.6) 657 (62.5) 1.15 (0.96-1.38) 0.13 POT1-03 rs33964002 G/A GG 482 (48.5) 460 (43.3) 1.00 (ref) GA 412 (41.5) 495 (46.5) 0.8 (0.6-0.9) 0.01 AA 99 (10.0) 108 (10.2) 0.9 (0.6-1.2) 0.34 GA/AA 511 (51.5) 603 (56.7) 0.79 (0.67-0.95) 0.01 POT1-04 rs12537161 C/T CC 382 (39.2) 428 (40.7) 1.00 (ref) CT 455 (46.6) 492 (46.9) 1.0 (0.9-1.2) 0.75 TT 139 (14.2) 130 (12.4) 1.2 (0.9-1.6) 0.17 CT/TT 594 (60.8) 622 (59.3) 1.07 (0.89-1.28) 0.47 POT1-07 rs7784168 A/G AA 482 (48.4) 467 (43.8) 1.00 (ref) AG 417 (41.8) 494 (46.3) 0.8 (0.7-0.9) 0.02 GG 98 (9.8) 105 (9.9) 0.9 (0.7-1.2) 0.47 AG/GG 515 (51.6) 599 (56.2) 0.82 (0.69-0.97) 0.02 POT1-08 rs7794637 G/A GG 470 (48.0) 460 (43.9) 1.00 (ref) GA 419 (42.7) 490 (46.8) 0.8 (0.7-0.9) 0.03 AA 91 (9.3) 97 (9.3) 0.9 (0.7-1.3) 0.58 GA/AA 510 (52.0) 587 (56.1) 0.83 (0.70-0.99) 0.04 POT1-09 rs10263573 T/A TT 360 (37.8) 406 (39.6) 1.00 (ref) TA 449 (47.2) 488 (47.6) 1.0 (0.9-1.3) 0.73 AA 143 (15.0) 131 (12.8) 1.2 (0.9-1.6) 0.12 TA/AA 592 (62.2) 619 (60.4) 1.08 (0.90-1.30) 0.41 POT1-11 rs10250202 T/G TT 376 (37.5) 428 (39.9) 1.00 (ref) TG 473 (47.2) 511 (47.6) 1.1 (0.9-1.3) 0.59 GG 153 (15.3) 134 (12.5) 1.3 (1.0-1.7) 0.04 TG/GG 626 (62.5) 645 (60.1) 1.11 (0.93-1.32) 0.26 POT1-18 rs1034794 A/T AA 476 (47.9) 469 (44.2) 1.00 (ref) AT 427 (43.0) 490 (46.1) 0.8 (0.7-1.0) 0.06 TT 91 (9.1) 103 (9.7) 0.9 (0.6-1.2) 0.34 AT/TT 518 (52.1) 593 (55.8) 0.85 (0.71-1.01) 0.06 POT1-44 rs727505 C/T CC 512 (51.6) 537 (50.7) 1.00 (ref) CT 407 (41.0) 440 (41.5) 1.0 (0.8-1.2) 0.72 TT 74 (7.4) 83 (7.8) 0.9 (0.7-1.3) 0.69 CT/TT 481 (48.4) 523 (49.3) 0.96 (0.81-1.15) 0.66 RAD18-01 rs373572 A/G AA 504 (51.3) 570 (53.5) 1.00 (ref) AG 414 (42.1) 419 (39.3) 1.1 (0.9-1.3) 0.21 GG 65 (6.6) 77 (7.2) 1.0 (0.7-1.4) 0.98 AG/GG 479 (48.7) 496 (49.5) 1.10 (0.93-1.31) 0.27 TERC-01 rs2293607 A/G AA 600 (60.9) 645 (61.7) 1.00 (ref) AG 331 (33.6) 360 (34.4) 1.0 (0.8-1.2) 0.92 GG 55 (5.5) 41 (3.9) 1.4 (0.9-2.2) 0.10 AG/GG 386 (39.2) 401 (38.3) 1.03 (0.86-1.24) 0.71 TERF1-01 rs2306492 G/A GG 441 (45.2) 462 (44.0) 1.00 (ref) GA 439 (45.0) 486 (46.3) 1.0 (0.8-1.1) 0.61 AA 95 (9.8) 102 (9.7) 1.0 (0.7-1.4) 0.96 GA/AA 534 (54.8) 588 (56.0) 0.96 (0.80-1.14) 0.64 TERF1-04 rs2306494 A/G AA 453 (45.6) 476 (44.8) 1.00 (ref) AG 437 (44.0) 478 (45.0) 1.0 (0.8-1.2) 0.67 GG 103 (10.4) 109 (10.2) 1.0 (0.7-1.3) 0.99 AG/GG 540 (54.4) 587 (55.2) 0.97 (0.81-1.15) 0.72 TERF1-06 rs3863242 C/T CC 319 (32.5) 315 (30.1) 1.00 (ref) CT 459 (46.8) 553 (52.8) 0.8 (0.7-1.0) 0.06 TT 203 (20.7) 180 (17.2) 1.1 (0.9-1.4) 0.42 CT/TT 662 (67.5) 733 (69.9) 0.90 (0.74-1.08) 0.26 TERF1-27 rs10106086 G/A GG 401 (41.4) 441 (42.9) 1.00 (ref) GA 459 (47.4) 478 (46.5) 1.1 (0.9-1.3) 0.60 AA 109 (11.2) 108 (10.5) 1.1 (0.8-1.5) 0.52 GA/AA 568 (58.6) 586 (57.1) 1.06 (0.89-1.27) 0.52 TERF2-01 rs153045 A/G AA 437 (45.0) 463 (44.3) 1.00 (ref) AG 412 (42.4) 455 (43.5) 1.0 (0.8-1.2) 0.73 GG 123 (12.6) 127 (12.2) 1.0 (0.8-1.4) 0.88 AG/GG 535 (55.0) 582 (55.7) 0.98 (0.82-1.17) 0.82 TERF2-03 rs35439397 G/A GG 663 (67.3) 723 (68.9) 1.00 (ref) GA 289 (29.3) 282 (26.9) 1.1 (0.9-1.3) 0.37 AA 33 (3.4) 44 (4.2) 0.8 (0.5-1.3) 0.37 GA/AA 322 (32.7) 326 (31.1) 1.06 (0.88-1.27) 0.57 TERF2-14 rs251796 T/C TT 477 (49.0) 513 (48.4) 1.00 (ref) TC 398 (40.9) 439 (41.5) 1.0 (0.8-1.2) 0.94 CC 99 (10.1) 107 (10.1) 1.0 (0.7-1.3)