Table 2.
Association results for top 15 DNA repair genes and 24 candidate PCa genes
| Gene | Rank/81a | Chr | No. of var | Carrier frequencies |
Aggressive vs nonaggressive |
Metastatic vs nonaggressive |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Non-agg | Agg | M1 | OR (95% CI) | P b | P adj | OR (95% CI) | P b | P adj | ||||
| Top 15 genes | ||||||||||||
| BRCA2 c | 1 | 13 | 59 | 0.00829 | 0.02491 | 0.01927 | 3.19 (1.94 to 5.25) | 8.58 x 10-7 d | 6.95 x 10-5 | 2.88 (1.22 to 6.83) | .02 | .25 |
| PALB2 c | 2 | 16 | 16 | 0.00108 | 0.00650 | 0.01071 | 6.31 (1.83 to 21.68) | 4.79 x 10-4 d | .02 | 7.71 (1.62 to 36.72) | .009 | .19 |
| TP53BP1 | 3 | 15 | 2 | 0.00360 | 0.00072 | 0 | 0.18 (0.04 to 0.86) | .01 | .36 | — | .07 | .51 |
| ATM c | 4 | 11 | 47 | 0.00757 | 0.01552 | 0.02141 | 1.88 (1.10 to 3.22) | .02 | .38 | 2.71 (1.19 to 6.2) | .02 | .25 |
| GEN1 c | 5 | 2 | 8 | 0.00396 | 0.00072 | 0 | 0.22 (0.05 to 1.02) | .03 | .42 | — | .23 | .64 |
| ALKBH3 | 6 | 11 | 5 | 0.00865 | 0.00469 | 0 | 0.50 (0.25 to 1.01) | .049 | .53 | — | .01 | .21 |
| APLF | 7 | 2 | 5 | 0.00216 | 0.00036 | 0 | 0.17 (0.02 to 1.44) | .05 | .53 | — | .06 | .51 |
| RECQL | 8 | 12 | 10 | 0.00757 | 0.00433 | 0 | 0.52 (0.25 to 1.07) | .07 | .53 | — | .005 | .19 |
| FANCG | 9 | 9 | 3 | 0.00180 | 0.00036 | 0 | 0.17 (0.02 to 1.55) | .07 | .53 | NA | NA | NA |
| MLH1 c | 10 | 3 | 11 | 0.00865 | 0.01227 | 0.01285 | 1.62 (0.94 to 2.82) | .08 | .53 | 2.15 (0.8 to 5.75) | .15 | .63 |
| FANCM | 11 | 14 | 11 | 0.00829 | 0.01300 | 0.01071 | 1.61 (0.93 to 2.79) | .08 | .53 | 1.1 (0.39 to 3.13) | .85 | .94 |
| DCLRE1C | 12 | 10 | 4 | 0.00180 | 0.00036 | 0 | 0.20 (0.02 to 1.72) | .09 | .53 | NA | NA | NA |
| MDC1 | 13 | 6 | 2 | 0.00180 | 0.00036 | 0 | 0.20 (0.02 to 1.78) | .10 | .53 | — | .31 | .72 |
| EXO1 | 14 | 1 | 6 | 0.00577 | 0.00975 | 0.00857 | 1.70 (0.90 to 3.23) | .10 | .53 | 1.43 (0.46 to 4.47) | .56 | .87 |
| FANCD2 | 15 | 3 | 4 | 0.00216 | 0.00072 | 0 | 0.28 (0.06 to 1.42) | .10 | .53 | — | .12 | .61 |
| Remaining candidate PCa DNA repair genes | ||||||||||||
| BRIP1 c | 16 | 17 | 7 | 0.00252 | 0.00072 | 0.00214 | 0.32 (0.06 to 1.59) | .13 | .67 | 0.93 (0.1 to 8.66) | .95 | .97 |
| CHEK2 c | 17 | 22 | 16 | 0.01405 | 0.01913 | 0.02141 | 1.38 (0.89 to 2.14) | .14 | .68 | 1.63 (0.76 to 3.51) | .23 | .64 |
| MUTYH c | 28 | 1 | 10 | 0.01333 | 0.01661 | 0.01713 | 1.27 (0.81 to 1.99) | .30 | .81 | 1.51 (0.67 to 3.4) | .34 | .73 |
| MSH2 c | 31 | 2 | 9 | 0.00108 | 0.00217 | 0.00214 | 2.06 (0.46 to 9.28) | .33 | .81 | NA | NA | NA |
| BRCA1 c | 37 | 17 | 15 | 0.00252 | 0.00361 | 0.00428 | 1.55 (0.56 to 4.29) | .39 | .85 | 2.11 (0.37 to 12.21) | .42 | .80 |
| MSH6 c | 39 | 2 | 8 | 0.00396 | 0.00578 | 0.00428 | 1.36 (0.62 to 2.98) | .44 | .89 | 1.19 (0.24 to 5.86) | .84 | .94 |
| MRE11A c | 41 | 11 | 8 | 0.00216 | 0.00144 | 0 | 0.61 (0.17 to 2.25) | .45 | .89 | — | .19 | .64 |
| ATR c | 48 | 3 | 9 | 0.01766 | 0.01552 | 0.01285 | 0.87 (0.57 to 1.34) | .53 | .90 | 0.81 (0.33 to 1.99) | .64 | .90 |
| NBN c | 50 | 8 | 6 | 0.00180 | 0.00144 | 0.00642 | 0.69 (0.18 to 2.60) | .58 | .93 | 4.11 (0.83 to 20.3) | .10 | .59 |
| WRN c | 52 | 8 | 7 | 0.00396 | 0.00542 | 0.00214 | 1.22 (0.55 to 2.74) | .62 | .96 | 0.48 (0.06 to 3.95) | .45 | .80 |
| PMS2 c | 62 | 7 | 7 | 0.00144 | 0.00108 | 0.00214 | 0.82 (0.17 to 3.96) | .81 | .98 | NA | NA | NA |
| FANCL c | 67 | 2 | 7 | 0.00973 | 0.00903 | 0.01071 | 1.05 (0.60 to 1.85) | .87 | .98 | 1.21 (0.44 to 3.35) | .72 | .92 |
| XPC c | 70 | 3 | 3 | 0.00108 | 0.00108 | 0.00214 | 1.14 (0.22 to 5.85) | .88 | .98 | NA | NA | NA |
| FAM175A c | 79 | 4 | 8 | 0.00180 | 0.00181 | 0 | 0.97 (0.26 to 3.60) | .97 | .98 | NA | NA | NA |
| ERCC2 c | 80 | 19 | 13 | 0.00324 | 0.00361 | 0.00642 | 0.98 (0.39 to 2.46) | .97 | .98 | 2.48 (0.59 to 10.46) | .24 | .64 |
| RAD51C c | — | 17 | 4 | 0.00036 | 0.00144 | 0 | NA | NA | NA | NA | NA | NA |
| RAD51D c | — | 17 | 2 | 0.00036 | 0.00072 | 0.00214 | NA | NA | NA | NA | NA | NA |
| SLX4 c | — | 16 | 5 | 0.00108 | 0.00072 | 0 | NA | NA | NA | NA | NA | NA |
| XRCC2 c | — | 7 | 4 | 0.00036 | 0.00108 | 0 | NA | NA | NA | NA | NA | NA |
Ranking is based on the P values for aggressive vs nonaggressive PCa. Em dash (—) = effect could not be calculated because no alleles were present in metastatic cases; Agg = aggressive cases; CI = confidence interval; M1 = metastatic cases; NA = test not performed because the minor allele count was 5 or less between nonaggressive and metastatic cases; Non-agg = nonaggressive cases; OR = odds ratio; P adj = Benjamini-Hochberg adjusted P values, calculated using an alpha 0.05; PCa = prostate cancer; Chr = chromosome; Var = number of pathogenic, likely pathogenic, and deleterious variants identified.
P values are calculated using the likelihood-ratio test. All tests of statistical significance are 2-sided.
Subset of 24 literature-curated candidate PCa genes.
Statistically significant.