The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients
Abstract
:1. Introduction
2. Results
2.1. Dose-Response Relationship between the Concentration of B6 and the Number of Viable Cells (NVC) in Cell Lines
2.2. Comparison of GSACV with Different B6 Concentrations in the Breast Cancer Cases or Controls
2.3. Comparison of GSACV at the Same B6 Concentration between the Breast Cancer Cases and Controls
2.4. Effect of B6 and Breast Cancer Status on GSACV
2.5. The GSACV Indexes in Different SHMT C1420T, MS A2756G, and MTRR A66G Genotypes in Breast Cancer Cases and Controls at Various B6 Concentrations
2.6. The Effects of the Strength and Variation Analysis of B6 and SHMT C1420T, MS A2756G, and MTRR A66G Polymorphisms on GSACV by Two-Way ANOVA
3. Discussion
3.1. Influences of B6 on GSACV
3.2. Influences of Genetic Polymorphisms on GSACV
3.3. Influences of Gene-Nutrient Interactions on GSACV
4. Materials and Methods
4.1. Cell Lines
4.2. Characteristics of the Study Population
4.3. Genotyping Analysis
4.4. Cell Lines and Lymphocytes Culture
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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B6 in Medium (nmol/L) ( ± SD) 1,2,3 | |||||||
---|---|---|---|---|---|---|---|
Endpoint | Group | 6 | 12 | 24 | 48 | 96 | 200 |
NDI | Cases | 1.30 ± 0.026 a | 1.28 ± 0.028 a | 1.29 ± 0.021 a | 1.36 ± 0.041 a | 1.30 ± 0.034 a | 1.30 ± 0.027 a |
Controls | 1.26 ± 0.027 a | 1.27 ± 0.031 a | 1.25 ± 0.015 a | 1.26 ± 0.030 a | 1.23 ± 0.027 a | 1.28 ± 0.025 a | |
‰ MNBN | Cases | 27.8 ± 2.05 a | 25.9 ± 1.60 b | 22.2 ± 3.24 b | 18.7 ± 2.44 c | 17.2 ± 1.62 c | 17.0 ± 2.63 c |
Controls | 20.4 ± 2.12 a | 17.4 ± 1.45 b | 15.7 ± 3.30 c | 13.6 ± 2.23 c,d | 12.07 ± 1.61 d | 13.44 ± 1.17 d | |
‰ MONO | Cases | 2.78 ± 0.45 a | 1.74 ± 0.40 b | 1.62 ± 0.65 b | 1.55 ± 0.53 b | 1.44 ± 0.23 b | 1.40 ± 0.42 b |
Controls | 2.05 ± 0.45 a | 1.59 ± 0.59 a | 1.49 ± 0.28 a,b | 1.30 ± 0.30 b | 1.29 ± 0.35 b | 1.33 ± 0.40 b | |
‰ NBUD | Cases | 9.30 ± 1.82 a | 7.98 ± 2.26 b | 6.13 ± 1.11 b,c | 5.96 ± 0.74 c | 5.43 ± 1.33 c | 6.02 ± 0.95 c |
Controls | 7.12 ± 1.07 a | 6.03 ± 1.52 b | 4.64 ± 1.42 b | 4.08 ± 1.44 b,c | 4.21 ± 1.07 b,c | 4.00 ± 0.68 c | |
‰ NPB | Cases | 5.36 ± 0.76 a | 4.93 ± 1.22 a | 3.76 ± 0.42 a,b | 3.41 ± 0.55 b | 3.08 ± 1.05 b | 3.11 ± 0.80 b |
Controls | 4.01 ± 0.27 a | 3.41 ± 0.56 a | 2.91 ± 0.67 b | 2.46 ± 0.60 b | 2.46 ± 1.02 b | 2.02 ± 0.12 b | |
% APO | Cases | 4.59 ± 0.80 a | 4.10 ± 0.67 a,b | 3.58 ± 1.10 b,c | 3.37 ± 1.11 b,c | 3.02 ± 0.95 b,c | 2.86 ± 0.97 c |
Controls | 5.22 ± 0.55 a | 5.09 ± 0.80 a,b | 5.71 ± 0.95 b,c | 5.25 ± 0.62 b,c | 4.24 ± 0.67 b,c | 3.97 ± 0.67 c | |
% NEC | Cases | 7.83 ± 0.53 a | 5.93 ± 0.40 b | 5.89 ± 0.60 b,c | 5.02 ± 0.78 c | 5.65 ± 0.63 c | 4.73 ± 0.73 c |
Controls | 6.37 ± 0.76 a | 5.79 ± 1.38 b | 4.65 ± 0.98 c | 4.05 ± 0.40 c | 3.85 ± 1.07 c | 3.69 ± 0.75 c |
B6 | MNBN | NBUD | NPB | MONO | APO | |
---|---|---|---|---|---|---|
MNBN | −0.764 *** | - | ||||
NBUD | −0.563 *** | 0.712 *** | - | |||
NPB | −0.615 *** | 0.538 *** | 0.426 ** | - | ||
MONO | −0.448 *** | 0.577 *** | 0.440 ** | 0.234 | - | |
APO | −0.761 *** | 0.739 *** | 0.502 *** | 0.356 * | 0.216 * | - |
NEC | −0.601 ** | 0.621 ** | 0.605 ** | 0.362 * | 0.516 ** | 0.523 ** |
B6 | MNBN | NBUD | NPB | MONO | APO | |
---|---|---|---|---|---|---|
MNBN | −0.582 *** | - | ||||
NBUD | −0.574 *** | 0.701 *** | - | |||
NPB | −0.609 *** | 0.620 *** | 0.419 ** | - | ||
MONO | −0.411 *** | 0.472 *** | 0.504 ** | 0.381 * | - | |
APO | −0.663 *** | 0.505 *** | 0.528 *** | 0.325 * | 0.372 * | - |
NEC | −0.510 *** | 0.610 *** | 0.592 *** | 0.430 ** | 0.654 ** | 0.550 ** |
Source of Variation | B6 | Status | Interaction |
---|---|---|---|
V% | V% | V% | |
MNBN | 46.15 *** | 5.12 * | 0.88 |
NPB | 30.13 ** | 4.14 * | 0.30 |
NBUD | 29.66 *** | 0.48 | 0.30 |
MONO | 3.14 | 0.04 | 1.56 |
APO | 31.65 *** | 0.61 | 1.87 |
NEC | 40.15 *** | 5.45 * | 2.44 |
GSACV | MNBN | MONO | NBUD | NPB | APO | NEC | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | |
Controls | ||||||||||||||||||
Genotype (SHMT) | 97.87 | 0.001 *** | 21.10 | 6.36 | 0.002 ** | 2.18 | 0.383 | 0.682 | 0.17 | 2.54 | 0.081 | 1.47 | 0.764 | 0.467 | 0.43 | 4.161 | 0.017 * | 2.31 |
B6 | 66.92 | 0.001 *** | 36.07 | 48.82 | 0.001 *** | 41.87 | 26.88 | 0.001 *** | 30.42 | 14.41 | 0.001 *** | 20.81 | 16.32 | 0.001 *** | 22.73 | 14.30 | 0.001 *** | 19.88 |
B6-genotype interaction | 1.677 | 0.087 | 1.81 | 1.83 | 0.056 | 3.14 | 1.755 | 0.07 | 3.97 | 0.78 | 0.647 | 2.25 | 0.82 | 0.609 | 2.29 | 1.009 | 0.436 | 2.81 |
Cases | ||||||||||||||||||
Genotype (SHMT) | 25.31 | 0.001 *** | 30.36 | 4.788 | 0.009 ** | 1.56 | 8.286 | 0.001 *** | 3.21 | 1.690 | 0.187 | 1.03 | 1.322 | 0.266 | 0.83 | 2.10 | 0.125 | 1.17 |
B6 | 49.97 | 0.001 *** | 16.58 | 26.51 | 0.001 *** | 21.6 | 12.33 | 0.001 *** | 11.94 | 4.720 | 0.001 *** | 7.19 | 8.377 | 0.001 *** | 13.09 | 4.071 | 0.002 ** | 5.68 |
B6-genotype interaction | 1.116 | 0.35 | 0.74 | 1.012 | 0.434 | 1.65 | 2.014 | 0.033* | 3.90 | 0.478 | 0.904 | 1.46 | 0.839 | 0.591 | 2.62 | 1.30 | 0.232 | 3.63 |
GSACV | MNBN | MONO | NBUD | NPB | APO | NEC | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | |
Controls | ||||||||||||||||||
Genotype (MS) | 5.134 | 0.007 ** | 1.31 | 2.147 | 0.119 | 0.76 | 3.334 | 0.037 * | 1.45 | 4.775 | 0.009 ** | 2.76 | 0.289 | 0.749 | 0.16 | 4.174 | 0.017 * | 2.18 |
B6 | 44.52 | 0.001 *** | 28.45 | 39.95 | 0.001 *** | 35.3 | 16.31 | 0.001 *** | 17.77 | 14.01 | 0.001 *** | 20.23 | 5.942 | 0.001 *** | 7.98 | 13.93 | 0.001 *** | 18.19 |
B6-genotype interaction | 3.465 | 0.001 *** | 4.43 | 1.89 | 0.046 * | 3.35 | 1.615 | 0.103 | 3.52 | 1.621 | 0.101 | 4.68 | 3.653 | 0.001 *** | 9.81 | 1.957 | 0.039 * | 5.11 |
Cases | ||||||||||||||||||
Genotype (MS) | 10.33 | 0.001 *** | 2.89 | 8.801 | 0.001 *** | 2.23 | 1.766 | 0.173 | 0.72 | 2.256 | 0.107 | 1.28 | 2.637 | 0.078 | 1.54 | 6.208 | 0.002 ** | 3.57 |
B6 | 29.62 | 0.001 *** | 20.68 | 37.41 | 0.001 *** | 23.69 | 19.57 | 0.001 *** | 19.86 | 8.249 | 0.001 *** | 11.68 | 4.779 | 0.001 *** | 6.98 | 8.837 | 0.001 *** | 12.71 |
B6-genotype interaction | 4.164 | 0.001 *** | 5.81 | 3.507 | 0.001 *** | 4.44 | 2.275 | 0.003 ** | 5.58 | 1.011 | 0.435 | 2.86 | 2.565 | 0.006 ** | 7.49 | 0.648 | 0.772 | 1.86 |
GSACV | MNBN | MONO | NBUD | NPB | APO | NEC | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | F | p | % of Variation | |
Controls | ||||||||||||||||||
Genotype (MTRR) | 0.626 | 0.536 | 0.19 | 0.383 | 0.682 | 0.13 | 0.221 | 0.801 | 0.10 | 2.229 | 0.11 | 1.33 | 1.117 | 0.329 | 0.64 | 0.265 | 0.877 | 0.04 |
B6 | 18.01 | 0.001 *** | 13.79 | 13.75 | 0.001 *** | 11.74 | 9.152 | 0.001 *** | 10.03 | 11.38 | 0.001 *** | 17.03 | 2.618 | 0.025 * | 3.37 | 3.534 | 0.004 ** | 5.09 |
B6-genotype interaction | 1.105 | 0.360 | 1.69 | 1.193 | 0.296 | 2.04 | 0.866 | 0.566 | 1.90 | 0.924 | 0.512 | 2.76 | 1.595 | 0.109 | 4.55 | 0.517 | 0.937 | 1.49 |
Cases | ||||||||||||||||||
Genotype (MTRR) | 2.625 | 0.075 | 0.84 | 5.499 | 0.005 ** | 1.40 | 3.36 | 0.036 * | 1.44 | 0.501 | 0.606 | 0.29 | 2.879 | 0.058 | 1.72 | 0.335 | 0.716 | 0.19 |
B6 | 33.38 | 0.001 *** | 26.69 | 51.12 | 0.001 *** | 32.47 | 23.67 | 0.001 *** | 25.31 | 8.116 | 0.001 *** | 11.95 | 9.355 | 0.001 *** | 13.95 | 12.31 | 0.001 *** | 17.72 |
B6-genotype interaction | 1.949 | 0.040 * | 3.12 | 4.457 | 0.001 *** | 5.66 | 0.919 | 0.516 | 1.97 | 0.610 | 0.805 | 1.80 | 1.845 | 0.054 | 5.50 | 1.502 | 0.139 | 4.32 |
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Wu, X.; Xu, W.; Zhou, T.; Cao, N.; Ni, J.; Zou, T.; Liang, Z.; Wang, X.; Fenech, M. The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients. Int. J. Mol. Sci. 2016, 17, 1003. https://doi.org/10.3390/ijms17071003
Wu X, Xu W, Zhou T, Cao N, Ni J, Zou T, Liang Z, Wang X, Fenech M. The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients. International Journal of Molecular Sciences. 2016; 17(7):1003. https://doi.org/10.3390/ijms17071003
Chicago/Turabian StyleWu, Xiayu, Weijiang Xu, Tao Zhou, Neng Cao, Juan Ni, Tianning Zou, Ziqing Liang, Xu Wang, and Michael Fenech. 2016. "The Role of Genetic Polymorphisms as Related to One-Carbon Metabolism, Vitamin B6, and Gene–Nutrient Interactions in Maintaining Genomic Stability and Cell Viability in Chinese Breast Cancer Patients" International Journal of Molecular Sciences 17, no. 7: 1003. https://doi.org/10.3390/ijms17071003