Table 2. MLH1 rs1800734, MSH2 rs2303426, MSH3 rs26279, EXO1 rs1047840 and EXO1 rs9350 single nucleotide polymorphism genotypes and EXO1 haplotypes in 90 patients with head and neck squamous cell carcinoma stratified by toxicity and response rate to concurrent chemoradiotherapy.
| Variable | Nephrotoxicity | Ototoxicity | Response rate | |||||
|---|---|---|---|---|---|---|---|---|
| G0 + G1 N (%) |
G2–G5 N (%) |
G0 + G1 N (%) |
G2–G4 N (%) |
CR + PR N (%) |
SD N (%) |
CR N (%) |
PR + SD N (%) |
|
| MLH1 rs1800734 | ||||||||
| GG + GA | 35 (52.2) | 32 (47.8) | 36 (52.2) | 33 (47.8) | 66 (93.0) | 5 (7.0) | 15 (21.1) | 56 (78.9) |
| AA | 1 (50.0) | 1 (50.0) | 0 (0.0) | 1 (100.0) | 2 (100.0) | 0 (0.0) | 0 (0.0) | 2 (100.0) |
| P-value | 0.99 | 0.99 | 0.99 | 0.99 | ||||
| OR (95% CI) | NE | NE | NE | NE | ||||
| GG | 20 (48.8) | 21 (51.2) | 20 (47.6) | 22 (52.4) | 42 (95.5) | 2 (4.5) | 9 (20.5) | 35 (79.5) |
| GA + AA | 16 (57.1) | 12 (42.9) | 16 (57.1) | 12 (42.9) | 26 (89.7) | 3 (10.3) | 6 (20.7) | 23 (79.3) |
| P-value | 0.29 | 0.46 | 0.10 | 0.47 | ||||
| OR (95% CI) | 1.76 (0.63–4.93) | 1.48 (0.53–4.13) | 0.13 (0.01–1.50) | 0.58 (0.13–2.55) | ||||
| MSH2 rs2303426 | ||||||||
| CC + CG | 29 (51.8) | 27 (48.2) | 27 (48.2) | 29 (51.8) | 54 (91.5) | 5 (8.5) | 10 (16.9) | 49 (83.1) |
| GG | 7 (53.8) | 6 (46.2) | 9 (64.3) | 5 (35.7) | 14 (100.0) | 0 (0.0) | 5 (35.7) | 9 (64.3) |
| P-value | 0.80 | 0.59 | 0.99 | 0.39 | ||||
| OR (95% CI) | 1.18 (0.33–4.24) | 1.43 (0.39–5.24) | NE | 2.01 (0.41–9.96) | ||||
| CC | 11 (61.1) | 7 (38.9) | 10 (55.6) | 8 (44.4) | 16 (94.1) | 1 (5.9) | 4 (23.5) | 13 (76.5) |
| CG + GG | 25 (49.0) | 26 (51.0) | 26 (50.0) | 26 (50.0) | 52 (92.9) | 4 (7.1) | 11 (19.6) | 45 (80.4) |
| P-value | 0.44 | 0.38 | 0.80 | 0.26 | ||||
| OR (95% CI) | 0.64 (0.21–1.98) | 0.59 (0.18–1.93) | 1.37 (0.12–15.71) | 0.42 (0.10–1.90) | ||||
| MSH3 rs26279 | ||||||||
| GG + GA | 31 (49.2) | 32 (50.8) | 31 (49.2) | 32 (50.8) | 65 (95.6) | 3 (4.4) | 14 (20.6) | 54 (79.4) |
| AA | 5 (83.3) | 1 (16.7) | 5 (71.4) | 2 (28.6) | 3 (60.0) | 2 (40.0) | 1 (20.0) | 4 (80.0) |
| P-value | 0.26 | 0.043 | 0.08 | 0.75 | ||||
| OR (95% CI) | 3.75 (0.38–37.03) | 10.29 (1.06–100.21) | 0.11 (0.01–1.31) | 1.49 (0.12–18.17) | ||||
| GG | 13 (35.1) | 24 (64.9) | 18 (46.2) | 21 (53.8) | 39 (95.1) | 2 (4.9) | 8 (19.5) | 33 (80.5) |
| GA + AA | 23 (71.9) | 9 (28.1) | 18 (58.1) | 13 (41.9) | 29 (90.6) | 3 (9.4) | 7 (21.9) | 25 (78.1) |
| P-value | 0.0071 | 0.13 | 0.61 | 0.56 | ||||
| OR (95% CI) | 4.27 (1.48–12.34) | 2.28 (0.79–6.58) | 0.60 (0.08–4.42) | 1.48 (0.39–5.59) | ||||
| EXO1 rs1047840 | ||||||||
| GG + GA | 34 (55.7) | 27 (44.3) | 33 (52.4) | 30 (47.6) | 60 (92.3) | 5 (7.7) | 14 (21.5) | 51 (78.5) |
| AA | 2 (25.0) | 6 (75.0) | 3 (42.9) | 4 (57.1) | 8 (100.0) | 0 (0.0) | 1 (12.5) | 7 (87.5) |
| P-value | 0.07 | 0.61 | 0.99 | 0.99 | ||||
| OR (95% CI) | 4.88 (0.86–27.55) | 0.64 (0.12–3.47) | NE | NE | ||||
| GG | 18 (56.3) | 14 (43.8) | 19 (61.3) | 12 (38.7) | 31 (93.9) | 2 (6.1) | 11 (33.3) | 22 (66.7) |
| GA + AA | 18 (48.6) | 19 (51.4) | 17 (43.6) | 22 (56.4) | 37 (92.5) | 3 (7.5) | 4 (10.0) | 36 (90.0) |
| P-value | 0.35 | 0.30 | 0.83 | 0.015 | ||||
| OR (95% CI) | 1.63 (0.59–4.51) | 0.58 (0.21–1.62) | 0.79 (0.10–6.56) | 9.55 (1.56–58.60) | ||||
| EXO1 rs9350 | ||||||||
| CC + CT | 36 (52.2) | 33 (47.8) | 36 (51.4) | 34 (48.6) | 68 (93.2) | 5 (6.8) | 15 (20.5) | 58 (79.5) |
| TT | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| P-value | 0.99 | 0.99 | 0.99 | 0.99 | ||||
| OR (95% CI) | NE | NE | NE | NE | ||||
| CC | 21 (42.0) | 29 (58.0) | 30 (57.7) | 22 (42.3) | 49 (94.2) | 3 (5.8) | 12 (23.1) | 40 (76.9) |
| CT | 15 (78.9) | 4 (21.1) | 6 (33.3) | 12 (66.7) | 19 (90.5) | 2 (9.5) | 3 (14.3) | 18 (85.7) |
| P-value | 0.022 | 0.06 | 0.60 | 0.27 | ||||
| OR (95% CI) | 4.69 (1.34–16.44) | 4.03 (1.17–13.93) | 0.59 (0.08–4.30) | 0.38 (0.07–2.15) | ||||
| EXO1 + EXO1 | ||||||||
| GT | 14 (87.5) | 2 (12.5) | 5 (31.3) | 11 (68.7) | 16 (88.9) | 2 (11.1) | 3 (16.7) | 15 (83.3) |
| Other haplotypes | 22 (41.5) | 31 (58.5) | 31 (57.4) | 23 (42.6) | 52 (94.5) | 3 (5.5) | 12 (21.8) | 43 (78.2) |
| P-value | 0.06 | 0.034 | 0.49 | 0.71 | ||||
| OR (95% CI) | 3.11 (1.85–44.75) | 4.00 (1.11–14.48) | 0.49 (0.07–3.72) | 0.71 (0.13–4.07) | ||||
| AC | 18 (48.6) | 19 (51.4) | 17 (43.6) | 22 (56.4) | 37 (92.5) | 3 (7.5) | 4 (10.0) | 36 (90.0) |
| Other haplotypes | 18 (56.3) | 14 (43.7) | 19 (61.3) | 12 (38.7) | 31 (93.9) | 2 (6.1) | 11 (33.3) | 22 (66.7) |
| P-value | 0.35 | 0.30 | 0.74 | 0.026 | ||||
| OR (95% CI) | 0.61 (0.22–1.70) | 0.58 (0.21–1.62) | 0.70 (0.08–5.90) | 9.55 (1.56–58.60) | ||||
G: grade of toxicity; N: number of patients; CR: complete response; PR: partial response; SD: stable disease; OR: odds ratio; CI: confidence interval; NE: not evaluated. ORs were adjusted by age, cumulative dose of cisplatin and body mass index in analyses of nephrotoxicity, by age, cumulative dose of cisplatin and tumor location in analyses of ototoxicity for age, cumulative dose of cisplatin, body mass index, tumor location and grade in analyses of response rate. The total number of patients differed from the total quoted in the study (N = 90) because it was not possible to obtain consistent information about response rate and toxicities in some cases; 1P bootstrap = 0.006, 2P bootstrap = 0.005, 3P bootstrap = 0.01, 4P bootstrap = 0.02, 5P bootstrap = 0.007, 6P bootstrap = 0.005.