Effect of HVEM/CD160 Variations on the Clear Cell Renal Carcinoma Risk and Overall Survival
Abstract
:1. Introduction
2. Results
2.1. Correlation of HVEM and CD160 Gene SNPs with ccRCC Susceptibility
2.2. Multifactorial Regression Analysis
2.3. Haplotype Analysis
2.4. Sex-Dependent Association of HVEM and CD160 Polymorphisms and ccRCC Risk
2.5. Association of HVEM and CD160 Polymorphisms with Clinical Features of ccRCC
2.6. Analysis of Patients’ Survival in Context of Clinical Parameters as Well as HVEM and CD160 Gene Polymorphisms
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Controls
4.3. Selection of SNPs
4.4. DNA Isolation and SNP Genotyping
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SNP | Genotype | Case | Control | OR (95% CI) | p Value * | ||
---|---|---|---|---|---|---|---|
N | % | N | % | ||||
rs1886730T > C | TT | 49 | 20.59 | 140 | 26.87 | 1 | 0.17 |
CT | 130 | 54.62 | 257 | 49.33 | 1.44 (0.98–2.12) | ||
CC | 59 | 24.79 | 124 | 23.80 | 1.36 (0.87–2.12) | ||
CT + CC | 189 | 79.41 | 381 | 73.13 | 1.41 (0.98–2.04) | 0.06 | |
TT + CT | 179 | 75.21 | 397 | 76.20 | 0.94 (0.66–1.35) | 0.77 | |
rs2234167G > A | GG | 167 | 70.17 | 404 | 77.54 | 1 | 0.06 |
AG | 68 | 28.57 | 108 | 20.73 | 1.52 (1.07–2.17) | ||
AA | 3 | 1.26 | 9 | 1.73 | 0.89 (0.26–3.07) | ||
AG + AA | 71 | 29.83 | 117 | 22.46 | 1.47 (1.04–2.07) | 0.03 | |
GG + AG | 235 | 98.74 | 512 | 98.27 | 1.25 (0.36–4.29) | 0.63 | |
rs8725G > A | GG | 52 | 21.85 | 145 | 27.83 | 1 | 0.22 |
AG | 125 | 52.52 | 252 | 48.37 | 1.38 (0.94–2.02) | ||
AA | 61 | 25.63 | 124 | 23.80 | 1.37 (0.88–2.12) | ||
AG + AA | 186 | 78.15 | 376 | 72.17 | 1.37 (0.96–1.97) | 0.08 | |
GG + AG | 177 | 74.37 | 397 | 76.20 | 0.90 (0.64–1.29) | 0.59 | |
rs744877C > A | CC | 77 | 32.35 | 173 | 33.21 | 1 | 0.95 |
AC | 118 | 49.58 | 258 | 49.52 | 1.03 (0.73–1.45) | ||
AA | 43 | 18.07 | 90 | 17.27 | 1.08 (0.69–1.69) | ||
AC + AA | 161 | 67.65 | 348 | 66.79 | 1.04 (0.75–1.44) | 0.82 | |
CC + AC | 195 | 81.93 | 431 | 82.73 | 0.94 (0.63–1.40) | 0.79 | |
rs2231375C > T | CC | 78 | 33.05 | 206 | 39.62 | 1 | 0.03 |
CT | 130 | 55.08 | 233 | 44.81 | 1.47 (1.05–2.06) | ||
TT | 28 | 11.86 | 81 | 15.58 | 0.92 (0.56–1.52) | ||
CT + TT | 158 | 66.95 | 314 | 60.38 | 1.33 (0.96–1.83) | 0.08 | |
CC + CT | 208 | 88.14 | 439 | 84.42 | 1.36 (0.86–2.14) | 0.18 |
ccRCC (n = 238) | Control (n = 521) | ||||
---|---|---|---|---|---|
A+, B+ | 39 | 57 | |||
A+, B− | 28 | 51 | |||
A−, B+ | 91 | 177 | |||
A−, B− | 78 | 236 | |||
Test | OR | p value * | 95% CI | Comparison | Individual association |
(a) A+ | 1.53 | 0.02 | 1.08–2.18 | ||
(b) B+ | 1.58 | 0.04 | 1.16–2.15 | ||
(c) A+ B+ vs. A−B+ | 1.33 | 0.24 | 0.82–2.15 | A in B positive | A association |
(d) A+ B− vs. A −B − | 1.85 | 0.02 | 1.09–3.13 | A in B negative | |
(e) A+ B+ vs. A+ B− | 1.25 | 0.48 | 0.67–2.31 | B in A positive | B association |
(f) A− B + vs. A − B− | 1.56 | 0.02 | 1.09–2.23 | B in A negative | |
(g) A + B− vs. A− B+ | 1.07 | 0.81 | 0.63–1.81 | Differences between A and B | |
(h) A +B + vs. A− B− | 2.07 | 0.003 | 1.30–3.35 | Combined association |
Logistic Regression | Regression Coefficient | Standard Error | p-Value * | OR | CI 95% | |
---|---|---|---|---|---|---|
Unifactorial Model | ||||||
rs2234167 | AA + AG | 0.38 | 0.18 | 0.029 | 1.47 | 1.04–2.07 |
rs8725 | G G | −0.32 | 0.18 | 0.082 | 0.72 | 0.50–1.04 |
rs1886730 | T T | −0.35 | 0.19 | 0.064 | 0.71 | 0.49–1.02 |
rs2231375 | C T | 0.41 | 0.16 | 0.010 | 1.50 | 1.10–2.05 |
Multifactorial Model | ||||||
rs2234167 | AA +AG | 0.26 | 0.19 | 0.16 | 1.30 | 0.90–1.88 |
rs8725 | G G | −0.09 | 0.33 | 0.80 | 0.92 | 0.48–1.75 |
rs1886730 | T T | −0.18 | 0.34 | 0.60 | 0.84 | 0.43–1.62 |
rs2231375 | C T | 0.39 | 0.16 | 0.015 | 1.47 | 1.08–2.01 |
Haplotype * | Case (%) | Control (%) | Odds Ratio [95% CI] | p Value ** |
---|---|---|---|---|
CAAAC | 15.23 (0.032) | 41.05 (0.039) | 0.79 [0.434~1.438] | 0.44 |
CAACT | 44.30 (0.094) | 42.11 (0.040) | 2.41 [1.55~3.73] | 5.78 × 10−5 |
CGAAC | 79.55 (0.179) | 156.46 (0.150) | 1.11 [0.83~1.50] | 0.48 |
CGACC | 29.73 (0.063) | 83.12 (0.080) | 0.75 [0.49~1.16] | 0.20 |
CGACT | 50.36 (0.107) | 111.32 (0.107) | 0.97 [0.68~1.38] | 0.86 |
TGGAC | 92.68 (0.196) | 189.24 (0.182) | 1.07 [0.81~1.41] | 0.65 |
TGGCC | 39.02 (0.083) | 102.89 (0.099) | 0.80 [0.54~1.17] | 0.25 |
TGGCT | 80.71 (0.171) | 201.04 (0.193) | 0.83 [0.62~1.11] | 0.21 |
Global χ2 = 20.33, df = 7, p = 0.005 |
N (Case/Control) | OR (95% CI); p Value * | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
rs1886730 | TT | CT | CC | CT + CC vs. TT | CT + TT vs. CC | CT vs. TT | CT vs. TT + CC | ||||
15/50 | 46/77 | 25/44 | 1.92 (1.01–3.64); | 0.04 | 0.84 (0.47–1.49); | 0.57 | 1.95 (0.99–3.84); | 0.05 | 1.40 (0.83–2.36); | 0.20 | |
rs2234167 | GG | AG | AA | AG + AA vs. GG | GG + AG vs. AA | AG vs. GG | AG vs. GG + AA | ||||
55/142 | 37/80 | 1/2 | 2.63 (1.46–4.73); | 0.001 | 0.84 (0.11–6.47); | 1.00 | 2.73 (1.50–4.96); | 0.001 | 2.76 (1.51–5.02); | 0.001 | |
rs8725 | GG | AG | AA | AG + AA vs. GG | GG + AG vs. AA | AG vs. GG | AG vs. GG + AA | ||||
14/56 | 47/74 | 25/41 | 2.45 (1.28–4.67); | 0.01 | 0.77 (0.43–1.37); | 0.38 | 2.48 (1.26–4.91); | 0.01 | 1.58 (0.94–2.66); | 0.09 | |
rs2231375 | CC | CT | TT | TT + CT vs. CC | CC + CT vs. TT | CT vs. CC | CT vs. CC + TT | ||||
28/77 | 47/65 | 10/28 | 1.67 (0.97–2.87); | 0.06 | 1.44 (0.67–3.08); | 0.32 | 1.97 (1.12–3.48); | 0.02 | 2.00 (1.18–3.39); | 0.01 |
Variable | All N = 238 | Male N = 151 | Female N = 86 |
---|---|---|---|
Age at diagnosis | |||
Median | 62 | 61 | 63 |
Mean | 62.61 | 62.01 | 63.67 |
Q1–Q3 | 56–70 | 56–68 | 58–71 |
Min, Max | 21, 85 | 21, 85 | 24, 85 |
BMI | |||
Median | 27.70 | 27.70 | 27.75 |
Mean | 28.29 | 28.26 | 28.33 |
Q1–Q3 | 24.6–31.5 | 25.1–30.7 | 23.85–31.2 |
Min, Max | 19.1, 43.8 | 19.7, 43.8 | 19.1, 43.8 |
Stage of disease | N (%) | N (%) | N (%) |
I | 108 (45.57) | 63 (41.72) | 45 (52.33) |
II | 26 (10.97) | 20 (13.25) | 6 (6.98) |
III | 26 (10.97) | 16 (10.60) | 10 (11.63) |
IV | 76 (32.07) | 51 (33.77) | 25 (29.07) |
Unknown | 1 (0.42) | 1 (0.66) | 0 (0) |
Metastasis | |||
No | 165 (69.62) | 101 (66.89) | 64 (74.42) |
Present | 53 (22.36) | 35 (23.18) | 18 (20.93) |
Unknown | 19 (8.02) | 15 (9.93) | 4 (4.65) |
Necrosis | |||
No | 118 (59.00) | 71 (55.47) | 47 (65.28) |
Present | 82 (41.00) | 57 (44.53) | 25 (34.72) |
Unknown | 0 (0) | 0 (0) | 0 (0) |
Tumor size | |||
<70 mm | 143 (60.34) | 87 (57.61) | 56 (65.12) |
>70 mm | 65 (27.42) | 48 (31.79) | 17 (19.77) |
Unknown | 29 (12.24) | 16 (10.60) | 13 (15.11) |
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Andrzejczak, A.; Małkiewicz, B.; Tupikowski, K.; Ptaszkowski, K.; Szydełko, T.; Karabon, L. Effect of HVEM/CD160 Variations on the Clear Cell Renal Carcinoma Risk and Overall Survival. Int. J. Mol. Sci. 2024, 25, 6860. https://doi.org/10.3390/ijms25136860
Andrzejczak A, Małkiewicz B, Tupikowski K, Ptaszkowski K, Szydełko T, Karabon L. Effect of HVEM/CD160 Variations on the Clear Cell Renal Carcinoma Risk and Overall Survival. International Journal of Molecular Sciences. 2024; 25(13):6860. https://doi.org/10.3390/ijms25136860
Chicago/Turabian StyleAndrzejczak, Anna, Bartosz Małkiewicz, Krzysztof Tupikowski, Kuba Ptaszkowski, Tomasz Szydełko, and Lidia Karabon. 2024. "Effect of HVEM/CD160 Variations on the Clear Cell Renal Carcinoma Risk and Overall Survival" International Journal of Molecular Sciences 25, no. 13: 6860. https://doi.org/10.3390/ijms25136860