The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Baseline Information
2.3. Study Outcomes
2.4. SNP Genotyping and Selection
2.5. Statistical Analysis
3. Results
3.1. Patient Baseline Characteristics
3.2. Gene-Level Association with CRC Survival
3.3. Single SNPs and CRC Survival
3.4. Associations between Haplotypes and CRC Survival
3.5. Gene-Diet Interactions
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | No. Patients (%) a | No. Deaths (%) a | MST (Years) | plog-rank |
---|---|---|---|---|
Age at diagnosis (years) b | 60.06 (±9.23) | 60.66 (±9.76) | - | - |
Sex | 0.005 | |||
Male | 330 (62.03) | 127 (69.40) | 6.28 | |
Female | 202 (37.97) | 56 (30.60) | 6.53 | |
Race | 0.009 | |||
White | 440 (96.92) | 133 (94.33) | 6.44 | |
Other | 14 (3.08) | 8 (5.67) | 4.66 | |
Stage at diagnosis | <0.001 | |||
Ⅰ | 94 (17.67) | 18 (9.84) | 6.41 | |
Ⅱ | 209 (39.29) | 58 (31.69) | 6.64 | |
Ⅲ | 178 (33.46) | 65 (35.52) | 6.42 | |
Ⅳ | 51 (9.59) | 42 (22.95) | 3.90 | |
Tumour location | 0.444 | |||
Colon | 341 (65.83) | 110 (62.86) | 6.40 | |
Rectum | 177 (34.17) | 65 (37.14) | 6.33 | |
MSI status | <0.001 | |||
MSS/MSI-L | 446 (88.49) | 168 (96.55) | 6.33 | |
MSI-H | 58 (11.51) | 6 (3.45) | 6.67 | |
Reported screening procedure | 0.059 | |||
Yes | 52 (11.45) | 10 (7.09) | 6.57 | |
No | 402 (88.55) | 131 (92.91) | 6.40 | |
BMI (kg/m2) | 8 (1.60) | 0.097 | ||
<18.5 | 138 (27.60) | 6 (3.57) | 4.69 | |
18.5–24.9 | 205 (41.00) | 41 (24.40) | 6.40 | |
25.0–29.9 | 149 (29.80) | 74 (44.05) | 6.40 | |
≥30.0 | 47 (27.98) | 6.33 | ||
Average drinks per week | 0.062 | |||
0.0 | 170 (39.44) | 46 (34.59) | 6.53 | |
0.0–6.9 | 138 (32.02) | 43 (32.33) | 6.42 | |
7.0–14.0 | 74 (17.17) | 23 (17.29) | 6.44 | |
>14.0 | 49 (11.37) | 21 (15.79) | 5.86 | |
Smoking status | 0.133 | |||
Yes | 375 (72.39) | 136 (77.71) | 6.36 | |
No | 143 (27.61) | 39 (22.29) | 6.41 | |
Red meat intake (servings/week) | 0.048 | |||
≤2.0 | 84 (16.47) | 25 (14.71) | 6.72 | |
2.1–3.0 | 257 (50.39) | 86 (50.59) | 6.42 | |
3.1–5.0 | 83 (16.27) | 34 (20.00) | 6.15 | |
>5.0 | 86 (16.86) | 25 (14.71) | 6.27 | |
Ever taken folate regularly | 0.236 | |||
Yes | 422 (93.99) | 128 (92.09) | 6.42 | |
No | 27 (6.01) | 11 (7.91) | 6.32 | |
Vitamin B12 (µg/day) | 9.03 (±6.06) | 9.58 (±5.50) | - | - |
Overall Survival HR (95% CI) a | Disease-Free Survival HR (95% CI) a | CRC-Specific Survival HR (95% CI) b | |||||||
---|---|---|---|---|---|---|---|---|---|
All | Colon | Rectum | All | Colon | Rectum | All | Colon | Rectum | |
MTRR | |||||||||
PC1 | 0.94 (0.77, 1.14) | 0.82 (0.64, 1.07) | 1.11 (0.79, 1.55) | 0.83 (0.69, 1.00) | 0.72 (0.56, 0.92) | 1.02 (0.74, 1.39) | 0.85 (0.63, 1.15) | 0.62 (0.37, 1.02) | 1.03 (0.66, 1.59) |
PC2 | 1.00 (0.83, 1.19) | 0.91 (0.72, 1.14) | 1.20 (0.86, 1.66) | 0.96 (0.82, 1.14) | 0.93 (0.75, 1.15) | 1.07 (0.80, 1.44) | 1.01 (0.78, 1.31) | 1.19 (0.81, 1.73) | 1.05 (0.62, 1.80) |
PC3 | 0.85 (0.70, 1.04) | 0.78 (0.61, 1.00) | 1.06 (0.72, 1.55) | 0.90 (0.75, 1.08) | 0.82 (0.66, 1.03) | 1.19 (0.85, 1.66) | 1.06 (0.84, 1.36) | 0.93 (0.67, 1.31) | 1.29 (0.81, 2.04) |
PC4 | 0.92 (0.75, 1.11) | 0.84 (0.64, 1.09) | 1.01 (0.71, 1.44) | 0.91 (0.77, 1.09) | 0.84 (0.66, 1.07) | 0.94 (0.70, 1.27) | 0.83 (0.63, 1.10) | 0.57 (0.37, 0.87) | 1.01 (0.63, 1.62) |
Global p | 0.414 | 0.082 | 0.794 | 0.149 | 0.015 | 0.843 | 0.533 | 0.025 | 0.863 |
MTHFR | |||||||||
PC1 | 1.22 (1.02, 1.46) | 1.23 (0.98, 1.55) | 1.17 (0.86, 1.59) | 1.13 (0.96, 1.33) | 1.16 (0.94, 1.43) | 1.05 (0.79, 1.40) | 1.78 (1.37, 2.31) | 2.08 (1.40, 3.08) | 1.64 (1.09, 2.48) |
PC2 | 0.92 (0.76, 1.11) | 0.86 (0.64, 1.15) | 0.84 (0.62, 1.15) | 0.93 (0.78, 1.11) | 0.92 (0.71, 1.18) | 0.96 (0.73, 1.27) | 1.01 (0.79, 1.29) | 0.98 (0.61, 1.59) | 0.88 (0.60, 1.27) |
PC3 | 1.11 (0.92, 1.33) | 1.08 (0.86, 1.35) | 1.32 (0.92, 1.90) | 1.09 (0.92, 1.29) | 1.08 (0.89, 1.32) | 1.13 (0.81, 1.58) | 1.21 (0.96, 1.52) | 1.41 (1.05, 1.89) | 1.08 (0.70, 1.66) |
PC4 | 1.03 (0.88, 1.20) | 1.14 (0.93, 1.39) | 0.85 (0.62, 1.16) | 1.04 (0.90, 1.20) | 1.11 (0.91, 1.35) | 0.96 (0.74, 1.24) | 0.93 (0.75, 1.15) | 1.19 (0.89, 1.59) | 0.55 (0.31, 0.96) |
PC5 | 0.96 (0.79, 1.16) | 0.99 (0.78, 1.26) | 0.77 (0.50, 1.19) | 1.04 (0.88, 1.24) | 1.05 (0.85, 1.30) | 0.94 (0.66, 1.35) | 1.32 (0.96, 1.81) | 1.60 (1.04, 2.47) | 0.93 (0.49, 1.78) |
Global p | 0.226 | 0.233 | 0.291 | 0.511 | 0.493 | 0.976 | 0.0005 | 0.0004 | 0.051 |
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Wang, Y.; Du, M.; Vallis, J.; Shariati, M.; Parfrey, P.S.; Mclaughlin, J.R.; Wang, P.P.; Zhu, Y. The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival. Nutrients 2022, 14, 4594. https://doi.org/10.3390/nu14214594
Wang Y, Du M, Vallis J, Shariati M, Parfrey PS, Mclaughlin JR, Wang PP, Zhu Y. The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival. Nutrients. 2022; 14(21):4594. https://doi.org/10.3390/nu14214594
Chicago/Turabian StyleWang, Yu, Meizhi Du, Jillian Vallis, Matin Shariati, Patrick S. Parfrey, John R. Mclaughlin, Peizhong Peter Wang, and Yun Zhu. 2022. "The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival" Nutrients 14, no. 21: 4594. https://doi.org/10.3390/nu14214594