Serum Vitamin Levels and Their Relationships with Other Biomarkers in Korean Breast Cancer Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Analytical Procedures
2.3. Statistical Analysis
3. Results
3.1. General Characteristics of the Study Population
3.2. Vitamin Status in the Study Population
3.3. Correlations among Vitamin Markers and Biochemical Factors
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Healthy Controls (n = 75) | Benign Breast Disease Patients (n = 62) | Breast Cancer Patients (n = 104) | p-Values b | ||
---|---|---|---|---|---|
Demographic characteristics | |||||
Age (years) a | 49 (39–54) | 43 (36–50) | 49 (44–55) | 0.001 c | |
Menopausal state | Pre-menopause, N (%) | 44 (58.7%) | 48 (77.4%) | 65 (62.5%) | 0.0551 |
Post-menopause, N (%) | 31 (41.3%) | 14 (22.6%) | 39 (37.5%) | ||
Body mass index (kg/m2) a | 22 (20–24) | 22 (20–24) | 23 (21–25) | 0.0059 | |
BMI < 23, N (%) | 47 (62.7%) | 43 (69.4%) | 50 (48.1%) | 0.0053 | |
23 ≤ BMI < 25, N (%) | 20 (26.7%) | 14 (22.6%) | 29 (27.9%) | ||
25 ≤ BMI, N (%) | 8 (10.7%) | 5 (8.1%) | 25 (24.0%) | ||
Serum chemistry results a | |||||
Total protein (g/dL) | 7.1 (6.9–7.5) | 7.3 (6.8–7.5) | 7.2 (6.9–7.4) | 0.9314 | |
Albumin (g/dL) | 4.4 (4.3–4.6) | 4.5 (4.3–4.7) | 4.4 (4.3–4.6) | 0.0549 | |
AST (U/L) | 19 (16–22) | 19 (16–22) | 17 (15–21) | 0.1009 | |
ALT (U/L) | 15 (11–20) | 14 (11–22) | 14 (12–18) | 0.8592 | |
ALP (U/L) | 55 (44–68) | 54 (41–69) | 56 (46–68) | 0.6366 | |
HDL (mg/dL) | 63 (52–75) | 64 (55–72) | 63 (51–74) | 0.8118 | |
LDL (mg/dL) | 116 (97–136) | 100 (89–128) | 108 (90–137) | 0.4161 | |
Total cholesterol (mg/dL) | 190 (174–215) | 167 (155–191) | 178 (160–206) | 0.0004 c |
Healthy Controls (n = 75) | Benign Breast Disease Patients (n = 62) | Breast Cancer Patients (n = 104) | p-Values b | Healthy Controls vs. Benign Breast Disease Patients | Healthy Controls vs. Breast Cancer Patients | Benign Breast Disease Patients vs. Breast Cancer Patients | |
---|---|---|---|---|---|---|---|
Serum Vitamin Concentrations a | p-Values c | p-Values c | p-Values c | ||||
Vitamin A (μmol/L) | 1.76 | 1.35 | 1.45 | <0.0001 | <0.0001 | <0.0001 | 0.4354 |
(1.52–2.16) | (1.16–1.60) | (1.18–1.70) | |||||
Vitamin D (ng/mL) | 18.0 | 15.8 | 14.7 | 0.0515 | 0.1478 | 0.0546 | 0.9812 |
(12.2–23.5) | (11.0–20.1) | (9.4–22.2) | |||||
Vitamin E (μmol/L) | 29.2 | 23.4 | 26.0 | <0.0001 | <0.0001 | 0.0006 | 0.1401 |
(26.1–37.2) | (20.3–27.4) | (21.6–31.5) | |||||
Methylmalonic acid (nmol/L) | 111.3 | 112.5 | 96.4 | 0.0378 | 0.9923 | 0.0812 | 0.0799 |
(78.5–170.4) | (80.9–165.1) | (73.5–127.3) | |||||
Homocysteine (μmol/L) | 8.0 | 8.2 | 7.8 | 0.8198 | 0.9913 | 0.824 | 0.9052 |
(6.9–9.5) | (6.7–9.9) | (6.6–9.4) |
Healthy Controls (n = 75) | Benign Breast Disease Patients (n = 62) | Breast Cancer Patients (n = 104) | ||
---|---|---|---|---|
Vitamin A (μmol/L) | OR (95% CI) | 1.00 | 0.17 (0.07–0.45) | 0.26 (0.12–0.57) |
p-values | <0.0001 | <0.0001 | ||
OR (95% CI) a | 1.00 | 0.13 (0.04–0.36) | 0.20 (0.08–0.48) | |
p-values | 0.0001 | 0.0004 | ||
Vitamin D (ng/mL) | OR (95% CI) | 1.00 | 0.99 (0.95–1.03) | 0.99 (0.96–1.03) |
p-values | 0.1478 | 0.0546 | ||
OR (95% CI) a | 1.00 | 0.98 (0.94–1.02) | 0.99 (0.95–1.02) | |
p-values | 0.3441 | 0.4358 | ||
Vitamin E (μmol/L) | OR (95% CI) | 1.00 | 0.92 (0.87–0.98) | 0.96 (0.92–1.01) |
p-values | <0.0001 | 0.0006 | ||
OR (95% CI) a | 1.00 | 0.97 (0.90–1.05) | 0.96 (0.91–1.02) | |
p-values | 0.4428 | 0.1867 | ||
Methylmalonic acid (nmol/L) | OR (95% CI) | 1.00 | 1.00 (1.00–1.01) | 1.00 (0.99–1.00) |
p-values | 0.9923 | 0.0812 | ||
OR (95% CI) a | 1.00 | 1.01 (1.00–1.01) | 1.00 (0.99–1.01) | |
p-values | 0.1169 | 0.6642 | ||
Homocysteine (μmol/L) | OR (95% CI) | 1.00 | 1.01 (0.85–1.20) | 1.01 (0.87–1.16) |
p-values | 0.9913 | 0.8240 | ||
OR (95% CI) a | 1.00 | 1.03 (0.86–1.23) | 0.99 (0.84–1.17) | |
p-values | 0.7615 | 0.8916 |
Vitamin A (μmol/L) | Vitamin D (ng/mL) | Vitamin E (μmol/L) | Methylmalonic Acid (μmol/L) | Homocysteine (μmol/L) | ||
---|---|---|---|---|---|---|
ER | Negative (n = 12) | 1.34 | 8.5 | 27.3 | 104.8 | 8.1 |
(1.16–1.67) | (7.1–15.8) | (22.3–29.0) | (85.8–163.4) | (6.5–9.6) | ||
Positive (n = 92) | 1.45 | 15.0 | 25.8 | 95.4 | 7.8 | |
(1.19–1.72) | (10.1–22.7) | (21.6–32.0) | (73.0–124.5) | (6.7–9.4) | ||
p-values b | 0.6145 | 0.0233 | 0.9959 | 0.2164 | 0.9756 | |
PR | Negative (n = 19) | 1.48 | 13.5 | 27.1 | 96.8 | 8.6 |
(1.13–1.86) | (8.0–22.9) | (21.9–29.1) | (84.0–173.4) | (7.2–10.2) | ||
Positive (n = 85) | 1.44 | 14.7 | 25.6 | 94.0 | 7.7 | |
(1.20–1.63) | (9.8–22.0) | (21.6–32.1) | (73.1–122.6) | (6.6–9.3) | ||
p-values b | 0.7144 | 0.6346 | 0.9062 | 0.2778 | 0.1288 | |
HER2 | Negative (n = 76) | 1.45 | 14.3 | 26.0 | 94.7 | 7.7 |
(1.19–1.70) | (9.1–21.9) | (21.7–31.6) | (73.0–125.7) | (6.5–9.2) | ||
Positive/Equivocal (n = 28) | 1.46 | 16.3 | 26.2 | 96.4 | 8.4 | |
(1.14–1.73) | (10.2–24.6) | (20.8–31.2) | (75.3–135.4) | (7.2–10.2) | ||
p-values c | 0.9357 | 0.5001 | 0.6788 | 0.8032 | 0.0946 | |
TN | No (n = 95) | 1.45 | 15.0 | 26.0 | 94.3 | 7.9 |
(1.17–1.69) | (9.8–22.5) | (21.6–31.7) | (73.1–124.4) | (6.6–9.4) | ||
Yes (n = 6) | 1.30 | 8.5 | 25.7 | 152.2 | 7.5 | |
(1.18–1.71) | (7.2–11.3) | (21.9–29.1) | (113.4–177.7) | (6.5–8.3) | ||
p-values b | 0.6011 | 0.0266 | 0.775 | 0.0384 | 0.4641 | |
LN metastasis | No (n = 88) | 1.45 | 15.0 | 25.8 | 94.3 | 7.8 |
(1.19–1.68) | (9.3–22.6) | (21.7–31.5) | (73.3–126.0) | (6.7–9.3) | ||
Yes (n = 16) | 1.38 | 13.4 | 26.6 | 108.3 | 8.8 | |
(1.14–1.93) | (9.7–20.3) | (20.5–31.7) | (80.7–134.5) | (6.5–10.3) | ||
p-values b | 0.8429 | 0.6654 | 0.9139 | 0.3605 | 0.502 | |
Stage | Stage 0~1/LCIS (n = 77) | 1.44 | 14.7 | 25.6 | 94.6 | 7.8 |
(1.18–1.67) | (9.0–22.3) | (21.6–31.3) | (73.4–127.6) | (6.6–9.2) | ||
Stage 2 (n = 19) | 1.48 | 16.0 | 25.1 | 103.3 | 8.7 | |
(1.28–1.86) | (9.3–22.8) | (21.6–30.2) | (82.5–131.0) | (6.8–10.2) | ||
Stage 3 (n = 8) | 1.19 | 14.0 | 31.7 | 94.3 | 7.9 | |
(1.04–1.89) | (11.3–18.5) | (22.9–35.8) | (75.0–110.5) | (6.5–9.6) | ||
p-values c | 0.5472 | 0.8976 | 0.447 | 0.6803 | 0.5515 |
Age | BMI | TP | Albumin | AST | ALT | ALP | HDL | LDL | TC | |
---|---|---|---|---|---|---|---|---|---|---|
Vitamin A | 0.298 c | 0.093 | −0.110 | −0.023 | 0.257 c | 0.261 c | 0.182 c | −0.026 | 0.096 | 0.183 c |
Vitamin D | 0.156 b | −0.08 | −0.032 | 0.059 | 0.196 c | 0.177 c | 0.026 | 0.096 | −0.015 | 0.015 |
Vitamin E | 0.292 c | 0.101 | 0.062 | −0.027 | 0.153 b | 0.186 c | 0.067 | 0.119 | 0.421 c | 0.586 c |
Methylmalonic acid | 0.164 b | −0.029 | −0.122 | −0.067 | 0.042 | −0.027 | 0.119 | 0.026 | 0.027 | 0.064 |
Homocysteine | 0.206 c | 0.137 b | 0.009 | −0.105 | 0.052 | 0.005 | 0.207 c | −0.159 b | 0.089 | 0.093 |
Studied Vitamins | Region | Numbers (Cases/Controls) | Analytes | Results | References |
---|---|---|---|---|---|
Vitamin A | Italy | 208 | Retinol (μmol/L) | BC patients (≥55 year-old) with low retinol levels had a poorer prognosis (hazard ratio = 3.58, 95% CI = 1.50–8.57). | Formelli, 2009 [24] |
Vitamin E | India | 75/75/50 a | α-tocopherol (ug/mL) | BC and BBD patients had significantly lower vitamin E levels (p < 0.001), and decreased vitamin E was directly related to higher stage BC. | Chitkara, 1996 [25] |
Vitamin A and E | USA | 105/203 | Retinol (μmol/L), α-tocopherol (μmol/L) | No evidence for protective effects of α-tocopherol or retinol in BC. | Dorgan, 1998 [26] |
Vitamin A and E | Sweden | 201/290 | Retinol (μmol/L), α-tocopherol (μmol/L) | No significant associations between plasma levels of α-tocopherol or retinol and BC risk. | Hultén, 2001 [27] |
Vitamin A and E | Korea | 160/229 | Retinol (μg/dL), α-tocopherol (μg/mL) | Significantly lower α-tocopherol and retinol levels in BC patients than in controls (p < 0.001). Significantly decreased BC risks with increasing α-tocopherol and retinol levels (α-tocopherol, OR = 0.13, 95% CI = 0.03–0.66; Retinol, OR = 0.08, 95% CI = 0.01–0.45) | Kim, 2001 [28] |
Vitamin A and E | Australia | 153/151 | Retinol (μmol/L), α-tocopherol (μmol/L) | Significant reduction of BC risk with increasing retinol levels (OR = 0.53, 95% CI 0.28–1.01, p = 0.04), but no significant association with BC risk and α-tocopherol levels (OR = 1.27, 95% CI = 0.69–2.35, N.S.) | Ching, 2002 [29] |
Vitamin A and E | USA | 969/969 | Retinol (μmol/L), α-tocopherol (μmol/L) | Retinol (p = 0.03) and α-tocopherol (p = 0.01) levels were associated with a significantly decreased risk of BC with LN metastasis. | Tamimi, 2005 [30] |
Vitamin A and E | France | 366/720 | Retinol (μmol/L), α-tocopherol (μmol/L) | No significant associations between BC risk and serum carotenoids (OR = 0.74, 95% CI = 0.47–1.16, N.S.), α-tocopherols (OR = 0.70, 95% CI = 0.44–1.13, N.S.), or retinol (OR = 0.85, 95% CI = 0.53–1.35, N.S.) in postmenopausal women. | Maillard, 2010 [31] |
Vitamin A and E | Korea | 376/304 | Retinol (μg/dL), α-tocopherol (μg/dL) | Higher retinol level was associated with lower BC risk (OR = 0.13, 95% CI = 0.07–0.26), but this was not true for α-tocopherol level. | Kim, 2010 [32] |
Vitamin D | USA | 701/724 | 25(OH)D (ng/mL), 1,25(OH)2D (ng/mL) | High levels of vitamin D were associated with lower BC risk, but this was not statistically significant (25(OH)D, RR = 0.73, 95% CI = 0.49–1.07, N.S.; 1,25(OH)2D, RR = 0.76, 95% CI = 0.52–1.11, N.S.). | Bertone-Johnson, 2005 [33] |
Vitamin D | Germany | 1394/1365 | 25(OH)D (nM) | Significant inverse association between vitamin D levels and post-menopausal BC risk (OR = 0.31, 95% CI = 0.24–0.42, p < 0.0001). | Abbas, 2008 [34] |
Vitamin D | USA | 1005/1005 | 25(OH)D (ng/mL), 1,25(OH)2D (pg/mL) | No inverse association between vitamin D levels and BC risk (25(OH)D, RR = 1.04, 95% CI = 0.75–1.45, N.S.; 1,25(OH)2D, RR = 1.23, 95% CI = 0.91–1.68, N.S.). | Freedman, 2008 [35] |
Vitamin D | USA | 1026/1075 | 25(OH)D (ng/mL) | Mean vitamin D levels were significantly lower in BC patients than in controls (p < 0.0001). There was an inverse association between vitamin D and BC risk in a concentration-dependent manner (p = 0.002). | Crew, 2009 [36] |
Vitamin D | Sweden | 764/764 | 25(OH)D2 (nmol/L), 25(OH)D3 (nmol/L) | Weak inverse association between 25(OH)D3 levels and BC risk, but this was not statistically significant. There was a weaker association between total 25(OH)D (25(OH)D2 + D3) and BC. | Almquist, 2010 [37] |
Vitamin D | USA | 579/574 | 25(OH)D (ng/mL) | Significantly lower vitamin D levels in BC patients (p < 0.001), and lower vitamin D levels in high grade BC, including ER(-) tumors (p ≤ 0.03) and TNBC (p = 0.002). | Yao, 2011 [38] |
Vitamin D | Korea | 310 b | 25(OH)D (ng/mL) | Vitamin D deficient individuals (<20 ng/mL) had increased risk of recurrence compared with those with sufficient vitamin D levels (30–150 ng/mL) (p = 0.002). Inverse association between vitamin D levels and prognosis of BC in luminal A (p = 0.012) and luminal B subtypes (p = 0.023), but no association with prognosis of BC in HER2(+) or TN subtypes. | Kim, 2011 [39] |
Vitamin D | Germany | 1295 b | 25(OH)D (nmol/L) | BC patients with lower vitamin D levels had a higher risk of death (hazard ratio = 1.08, 95% CI = 1.00–1.17) and significantly higher risk of distant recurrence (hazard ratio = 1.14, 95% CI = 1.05–1.24). | Vrieling, 2011 [40] |
Vitamin D | Pakistan | 90/90 | 25(OH)2D (ng/mL) | Significantly lower vitamin D levels in BC patients than in controls (p < 0.001). However, no significant association between tumor characteristics and vitamin D levels among BC patients. | Imtiza, 2012 [41] |
Vitamin D | USA | 194/194 | 25(OH)D (ng/mL) | Significantly lower vitamin D levels in BC patients than in controls (p = 0.02). Patients with suboptimal vitamin D levels (<32 ng/mL) had significantly higher risk of having ER(-) (OR = 2.59, 95% CI = 1.08–6.23) and TN (OR = 3.15, 95% CI = 1.05–9.49) BC than those with optimal vitamin D levels (≥32 ng/mL). BC patients with a basal-like subtype had lower vitamin D levels than BC patients with a luminal subtype (p = 0.04). | Peppone, 2012 [42] |
Vitamin D | Korea | 3634/17,133 | 25(OH)D (ng/mL) | Significantly higher BC risk in women with vitamin D deficiency than those with sufficient vitamin D (OR = 1.27, 95% CI = 1.15–1.39). Significant inverse association between vitamin D levels and HR(-) BC, particularly TNBC (OR = 1.45, 95% CI 1.15–1.82). | Park, 2015 [43] |
Vitamin D | Sweden | 764/764 | 25(OH)D3 (nmol/L) | Women with vitamin D levels of ≥77 but ≤97 nmol/L had a significantly lower risk of an ER(-) tumor (OR = 0.46, 95% CI = 0.23–0.94), PR(-) (OR = 0.66, 95% CI = 0.46–0.96) and higher Ki67 tumor expression (OR = 0.57, 95% CI = 0.36–0.90) than those with vitamin D levels of ≤76 nmol/L. | Shirazi, 2016 [44] |
Vitamin D | Brazil | 192 b | 25(OH)D (ng/mL) | Patients insufficient (20–29 ng/mL) or deficient (<20 ng/mL) for vitamin D had higher proportions of high-grade BC, advanced BC, metastatic disease, number of positive LNs, and high Ki-67 expression in their tumors (p < 0.05). | de Sousa Almeida-Filho, 2017 [45] |
Vitamin B12 | USA | 195/195 | Folate (ng/mL), Vitamin B12 (pg/mL) Homocysteine (nmol/mL) | Significantly lower vitamin B12 levels in BC in postmenopausal women (p = 0.03). Women with lower vitamin B12 levels showed increased BC risk (OR = 4.00, 95% CI = 1.05–15.20). No association between folate and homocysteine and BC risk. | Wu, 1999 [46] |
Vitamin B12 | USA | 712/712 | Folate (ng/mL), Vitamin B12 (pg/mL), Homocysteine (nmol/mL) | Significantly lower folate concentrations in BC than in controls (p = 0.009). Inverse association between vitamin B12 levels and risk of BC only among premenopausal women (RR = 0.36, 95% CI = 0.15–0.86). No association between homocysteine and BC risk. | Zhang, 2003 [47] |
Vitamin B12 | USA | 848/848 | Folate (ng/mL), Vitamin B12 (pg/mL) | No significant association between folate and vitamin B12 levels and overall risk of BC. Higher folate levels were associated with an increased risk of premenopausal BC (p = 0.04). | Lin, 2008 [48] |
Vitamin B12 | USA | 812/812 | Cysteine (nmol/mL), Homocysteine (nmol/mL) | Positive association between cysteine levels and BC risk (RR = 1.65, 95% CI = 1.04–2.61, p = 0.04). Patients who had low folate levels tend to have positive correlations between concentrations of homocysteine and cysteine and risk of BC development (p = 0.04 and 0.002). No association between homocysteine and overall BC risk. | Lin, 2010 [49] |
Vitamin B12 | Canada | 164 b | Folate (ng/mL), Vitamin B12 (pmol/L) | Significant association between high plasma folate levels (>24.4 ng/mL) and increased BC risk (HR = 3.20, 95% CI = 1.03–9.92, p = 0.04) than low folate (≤24.4 ng/mL). No significant association between vitamin B12 concentration and BC risk. | Kim, 2016 [50] |
Vitamin B12 | USA | 610/1207 | Folate (ng/mL), Vitamin B12 (pg/mL), Homocysteine (nmol/mL) | Plasma vitamin B12 was positively associated with higher risk of overall BC (95% CI = 1.17–2.29, p = 0.02), and plasma folate was positively associated with risk of invasive BC. | Houghton, 2019 [51] |
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Kim, J.A.; Choi, R.; Won, H.; Kim, S.; Choi, H.J.; Ryu, J.M.; Lee, S.K.; Yu, J.; Kim, S.W.; Lee, J.E.; et al. Serum Vitamin Levels and Their Relationships with Other Biomarkers in Korean Breast Cancer Patients. Nutrients 2020, 12, 2831. https://doi.org/10.3390/nu12092831
Kim JA, Choi R, Won H, Kim S, Choi HJ, Ryu JM, Lee SK, Yu J, Kim SW, Lee JE, et al. Serum Vitamin Levels and Their Relationships with Other Biomarkers in Korean Breast Cancer Patients. Nutrients. 2020; 12(9):2831. https://doi.org/10.3390/nu12092831
Chicago/Turabian StyleKim, Jee Ah, Rihwa Choi, Hojeong Won, Seonwoo Kim, Hee Jun Choi, Jai Min Ryu, Se Kyung Lee, Jonghan Yu, Seok Won Kim, Jeong Eon Lee, and et al. 2020. "Serum Vitamin Levels and Their Relationships with Other Biomarkers in Korean Breast Cancer Patients" Nutrients 12, no. 9: 2831. https://doi.org/10.3390/nu12092831
APA StyleKim, J. A., Choi, R., Won, H., Kim, S., Choi, H. J., Ryu, J. M., Lee, S. K., Yu, J., Kim, S. W., Lee, J. E., & Lee, S.-Y. (2020). Serum Vitamin Levels and Their Relationships with Other Biomarkers in Korean Breast Cancer Patients. Nutrients, 12(9), 2831. https://doi.org/10.3390/nu12092831