Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway as Survival Biomarkers in Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Ethic Statement
2.3. Study Population
2.4. Sociodemographic and Clinical Variables
2.5. Genetic Variables
2.5.1. DNA Isolation
2.5.2. Detection of Gene Polymorphisms
2.6. Survival Variables
2.7. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Influence of Clinical-Pathological Characteristics on Survival
3.2.1. Overall Survival
3.2.2. Progression-Free Survival
3.3. Genotypes and Haplotypes Distribution
3.4. Influence of Gene Polymorphisms and Haplotypes on Survival
3.4.1. Overall Survival
3.4.2. Progression-Free Survival
4. Discussion
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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Gene | dbSNP ID | Location | Alleles | Assay ID |
---|---|---|---|---|
VDR (12q13.11) | rs1544410 (BsmI) | Intron 8 | C > T | C___8716062_20 |
rs11568820 (Cdx2) | Intron 1 | C > T | C___2880808_10 | |
rs2228570 (FokI) | Exon 2 | A > G | C__12060045_20 | |
rs7975232 (ApaI) | Intron 8 | C > A | C__28977635_10 | |
rs731236 (TaqI) | Exon 9 | A > G | C___2404008_10 | |
CYP27B1 (12q14.1) | rs4646536 | Intron 6 | A > G | C__25623453_10 |
rs3782130 | 5′ Promoter | G > C | ANGZRHH 1 | |
rs10877012 | 5′ UTR | G > T | C__26237740_10 | |
rs703842 | 3′ UTR | A > G | AN9HX2K 1 | |
CYP24A1 (20q13.2) | rs6068816 | Exon 6 | C > T | C__25620091_20 |
rs4809957 | 3′ UTR | A > G | C___3120981_20 | |
CYP2R1 (11p15.2) | rs10741657 | 5′ UTR | A > G | C___2958430_10 |
GC (4q13.3) | rs7041 | Exon 11 | A > C | C___3133594_30 |
Variable | Baseline | ||
---|---|---|---|
N | % | Mean ± Standard Deviation | |
Sex | 127 | 100 | |
Female | 42 | 33.07 | - |
Male | 85 | 66.93 | - |
Family history of cancer | |||
Yes | 64 | 50.39 | - |
No | 63 | 49.61 | - |
Family history of CRC | |||
Yes | 27 | 21.26 | - |
No | 100 | 78.74 | - |
Smoking status | |||
Smokers | 27 | 21.26 | - |
Ex-smokers | 44 | 34.65 | - |
Nonsmokers | 56 | 44.09 | - |
Drinking status | |||
Drinkers | 24 | 18.90 | - |
Ex-drinkers | 7 | 5.51 | - |
Nondrinkers | 96 | 75.59 | - |
Body mass index (BMI) | |||
<24 | 27 | 21.26 | - |
>24 | 100 | 78.74 | - |
Type of CRC | |||
Colon | 89 | 70.08 | - |
Rectum | 38 | 29.92 | - |
Age of diagnosis | 127 | - | 62.52 ± 10.55 |
ECOG score | |||
0–1 | 116 | 91.34 | - |
2.4 | 11 | 8.66 | - |
Histopathology | |||
ADC | 107 | 84.25 | - |
Mucinous ADC | 20 | 15.75 | - |
Tumor size | 127 | - | 4.40 (3.00–5.50) |
Lymph node involvement | |||
Yes | 92 | 72.44 | - |
No | 35 | 27.56 | - |
Number of lymph node involvement | |||
None | 35 | 27.56 | - |
1 | 61 | 48.03 | - |
2 | 31 | 24.41 | - |
Histological grade | |||
Grade 1 | 18 | 14.17 | - |
Grade 2 | 94 | 74.02 | - |
Grade 3 | 15 | 11.81 | - |
Metastasis | |||
Yes | 36 | 28.35 | - |
No | 91 | 71.65 | - |
Stage | |||
I, II, or IIIA | 71 | 55.91 | - |
IIIB, IV, or IVB | 56 | 44.09 | - |
TNM stage | |||
I/II | 11 | 8.66 | - |
III/IV | 116 | 91.34 | - |
Primary tumor resection | |||
Yes | 119 | 93.70 | - |
No | 8 | 6.30 | - |
Adjuvant chemotherapy | |||
Fluoropyrimidines | 35 | 27.56 | - |
Fluoropyrimidines + Oxiplatin | 70 | 55.12 | - |
Fluoropyrimidines + Biological drugs | 19 | 14.96 | - |
None | 3 | 2.36 | - |
Survival | |||
PFS | 127 | - | 73.3 (41.0-NR) |
OS | 127 | - | 82.3 (62.1-NR) |
Overall Survival | ||
---|---|---|
Independent Variables | HR (CI95%) | p-Value |
Family history of CRC (No) | 1.442 (0.268–1.792) | 0.449 |
Stage (IIIB, IV, or IVB) | 1.130 (0.311–4.104) | 0.852 |
Adjuvant chemotherapy (Fluoropyrimidines) | 1.455 (0.595–3.558) | 0.411 |
Adjuvant chemotherapy (Fluoropyrimidines + biologics drugs) | 4.248 (1.655–10.904) | 0.003 |
Adjuvant chemotherapy (None) | 5.148 (0.507–52.332) | 0.166 |
Lymph node involvement (Yes) | 1.503 (0.751–3.006) | 0.249 |
ECOG score (2–4) | 1.342 (0.505–3.568) | 0.555 |
Metastasis (yes) | 1.360 (0.335–5.548) | 0.664 |
Age of CRC diagnosis | 1.067 (1.029–1.107) | <0.001 |
CYP24A1 rs6068816 (TT vs. C) | 6.237 (2.297–16.936) | <0.001 |
GC rs7041 (C vs. AA) | 4.939 (1.578–15.457) | 0.006 |
VDR rs7975232 (ApaI) (AA vs. C) | 1.974 (1.045–3.731) | 0.036 |
Overall Survival | ||
---|---|---|
Independent Variables | HR (CI95%) | p-Value |
Age of CRC diagnosis | 1.055 (1.023–1.090) | 0.001 |
ECOG score (2–4) | 1.029 (0.412–2.577) | 0.950 |
Lymph node involvement (Yes) | 1.994 (0.982–4.049) | 0.056 |
Metastasis (yes) | 3.142 (1.096–9.004) | 0.033 |
Stage (IIIB, IV, or IVB) | 1.268 (0.452–3.556) | 0.651 |
Primary tumor resection (No) | 1.271 (0.311–1.992) | 0.613 |
Adjuvant chemotherapy (Fluoropyrimidines) | 2.306 (1.059–5.019) | 0.035 |
Adjuvant chemotherapy (Fluoropyrimidines + biologics drugs) | 1.861 (0.823–4.208) | 0.135 |
Adjuvant chemotherapy (None) | 1.870 (0.231–15.143) | 0.557 |
CYP24A1 rs6068816 (TT vs. C) | 6.095 (2.413–15.398) | <0.001 |
GC rs7041 (A vs. CC) | 1.543 (1.143–1.935) | 0.268 |
VDR rs2228570 (FokI) (G vs. AA) | 1.003 (0.412–2.420) | 0.999 |
VDR rs7975232 (ApaI) (AA vs. C) | 1.692 (1.402–2.092) | 0.066 |
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Pérez-Durán, C.; Márquez-Pete, N.; Gálvez-Navas, J.M.; Cura, Y.; Rojo-Tolosa, S.; Pineda-Lancheros, L.E.; Ramírez-Tortosa, M.; García-Collado, C.; Maldonado-Montoro, M.d.M.; Villar-del-Moral, J.M.; et al. Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway as Survival Biomarkers in Colorectal Cancer. Cancers 2023, 15, 4077. https://doi.org/10.3390/cancers15164077
Pérez-Durán C, Márquez-Pete N, Gálvez-Navas JM, Cura Y, Rojo-Tolosa S, Pineda-Lancheros LE, Ramírez-Tortosa M, García-Collado C, Maldonado-Montoro MdM, Villar-del-Moral JM, et al. Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway as Survival Biomarkers in Colorectal Cancer. Cancers. 2023; 15(16):4077. https://doi.org/10.3390/cancers15164077
Chicago/Turabian StylePérez-Durán, Carmen, Noelia Márquez-Pete, José María Gálvez-Navas, Yasmin Cura, Susana Rojo-Tolosa, Laura Elena Pineda-Lancheros, MCarmen Ramírez-Tortosa, Carlos García-Collado, María del Mar Maldonado-Montoro, Jesús María Villar-del-Moral, and et al. 2023. "Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway as Survival Biomarkers in Colorectal Cancer" Cancers 15, no. 16: 4077. https://doi.org/10.3390/cancers15164077
APA StylePérez-Durán, C., Márquez-Pete, N., Gálvez-Navas, J. M., Cura, Y., Rojo-Tolosa, S., Pineda-Lancheros, L. E., Ramírez-Tortosa, M., García-Collado, C., Maldonado-Montoro, M. d. M., Villar-del-Moral, J. M., Pérez-Ramírez, C., & Jiménez-Morales, A. (2023). Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway as Survival Biomarkers in Colorectal Cancer. Cancers, 15(16), 4077. https://doi.org/10.3390/cancers15164077