Table 2.
Analyses of the entire CHEK2 coding sequence (separately or as part of panel NGS) or analyses of specific variant(s) in prostate cancer (PrC) patients.
| Reference | Population | P: Patients C: Controls |
Analysis ** | Odds Ratio (95% Confidence Interval); p—Remark (Statistically Insignificant in Italics) |
|---|---|---|---|---|
| Brandao 2020 [202] |
PT PRACTICAL |
P: 462 early-onset/familial PrC C: 710 PMC P: 55,162 PrC/C: 36,147 |
c.349A>G (p.R117G) |
7.7 (0.9–66.6); 0.06—PT PrC p.R117G 1.9 (1.1–3.2); 0.04—PRACTICAL PrC p.R117G |
| Momozawa 2018 [144] |
JP | P: 7636 C: 12,366 |
Panel NGS (8 genes) | 2.43 (0.91–6.86); 0.06 |
| Conti 2017 [203] |
AAPC, GH | AAPC–P:4,853 PrC; C: 4678 GH–P: 474; C: 458 |
GWAS array (rs78554043 = rs17886163; CHEK2 c.1343T>G; p.I448S) | 1.60 (1.27–2.00); 5.02 × 10−5—for AAPC PrC 2.45 (1.33–4.52); 0.004—for Ghana PrC |
| Naslund-Koch 2016 [156] | DK | 86,975 individuals (longitudinal study); 1340 developed PrC | c.1100delC | 1.60 (1.00–2.56); 0.05 |
| Southey 2016 [157] |
OCAC | P: 22,301 PrC C: 22,320 PMC |
iCOGS array incl. 6 rare CHEK2 variants |
1.46 (0.71–3.02); 0.3—for p.R117G 1.02 (0.73–1.44); 0.9—for p.R180C 1.47 (0.41–5.35); 0.6—for p.E239K 1.07 (0.28–4.07); 0.9—for p.D438Y 2.21 (1.06–4.63); 0.03—for p.D438Y 3.03 (1.53–6.03); 0.001—for I448S in Africans |
| Pritchard 2016 [118] |
US, UK | P: 692 metastat. PrC C: ExAC/TCGA |
Panel NGS | 3.1 (1.5–5.6); 0.002—vs. ExAC (excl. p.I157T) 4.7 (2.2–8.5); <0.001—vs. TCGA (excl. p.I157T) |
| Wang 2015 [204] |
meta | P: 6409 PrC C: 11,634 |
c.1100delC c.444+1G>A p.I157T |
3.29 (1.85–5.85); <0.001—c.1100delC 1.59 (0.79–3.20); 0.20—c.1100delC, familial 1.58 (0.93–2.71); 0.09—c.444+1G>A 1.80 (1.51–2.14); <0.001—p.I157T |
| Hale 2014 [205] |
meta | P: 5,124 PrC C: 9,258 |
c.1100delC | 1.98 (1.23–3.18); 0.004—unselected 3.39 (1.78–6.47); 0.0001—familial |
| Cybulski 2006 [206] |
PL | P: 1864 PrC (incl. 249 famil.) C: 5496 |
c.1100delC; c.444+1G>A; 5395del; p.I157T |
2.3 (1.1–3.9); <0.001—truncations, sporadic 4.7 (2.5–9.0); <0.001—truncations, familial 1.6 (1.3–2.0); <0.001—p.I157T, sporadic 2.7 (1.8–4.1); <0.001—p.I157T, familial |
| Weischer 2007 [162] |
DK | P: 116 PrC (prospective) C: 3999 PMC men (prospect.) |
c.1100delC | 2.3 (0.6–9.5) PrC prospective study |
| Johnson 2005 [177] |
UK | P: 469 bilat. BC | c.1100delC | 2.41 (1.67–3.36)—risk of PrC for relatives of patients with bilateral BC |
| Cybulski 2004 [20] |
PL | P: 690 PrC C: 4000 PMC |
c.1100delC; c.444+1G>A; p.I157T |
2.2; 0.04—truncations 1.7; 0.002—p.I157T |
| Seppala 2003 [207] |
FI | P1: 537 unselected PrC; P2: 120 hereditary PrC C: 510 non-PrC men |
CHEK2 (SSCP: heredit. PrC) c.1100delC/p.I157T |
3.14 (0.65–15.16); 0.15—c.1100delC, sporadic 8.24 (1.49–45.54); 0.02—c.1100delC, hereditary 1.48 (0.89–2.46); 0.13—p.I157T, sporadic 2.12 (1.06–4.27); 0.04—p.I157T, hereditary |
| Dong 2003 [200] |
US | P1: 400 sporadic PrC; P2: 298 familial PrCC: 510 non-PrC men |
CHEK2 (DHPLC) | 2.71 (1.04–7.04); 0.049 *—sporadic PrC 2.66 (0.98–7.28); 0.078 *– familial PrC 6.84 (0.86–54.1); 0.05 *—sporadic (w/o p.I157T) 5.74 (0.64–51.5); 0.17 *—familial (w/o p.I157T) |
* Calculated using WINPEPI [208]; ** CHEK2 = an analysis of the entire coding sequence (dominantly without CNV); otherwise specified if certain CHEK2 variants were genotyped. AAPC—African Ancestry Prostate Cancer; DK—Denmark; ES—Spain; ExAC—Exome Aggregation Consortium; FI—Finland; GH—Ghana; meta—meta-analysis; JP—Japan; OCAC—Ovarian Cancer Association Consortium; PL—Poland; PT—Portugal; PMC—population-matched control; PRACTICAL - The Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome; TCGA - The Cancer Genome Atlas; US—the USA. The analyses that failed to demonstrate an association are shown in italics.