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1Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
2Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea
3Cancer Research Institute, Seoul National University, Seoul, Korea
4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
5Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
6Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
7Division of Surgery, Thyroid Center, Seoul National University Cancer Hospital, Seoul, Korea
8Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, Korea
9Department of Family Medicine, Dongguk University College of Medicine, Gyeongju, Korea
Copyright © 2021 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Model 1: Function(Y)=β0+β1 (UIC)
Model 2: Function(Y)=β0+β1 (UIC)+β2 (free T4)+β3 (TSH)
Model 3: Function(Y)=β0+β1 (UIC)+β2 (free T4)+β3 (TSH)+β4 (age)+β5 (sex)+β6 (total energy intake)+β7 (education)+β8 (family history of cancer)+β9 (benign thyroid disease)+β10 (dyslipidemia),
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
AUTHOR CONTRIBUTIONS
Conception or design: K.K., K.E.L., S.K.P. Acquisition, analysis, or interpretation of data: K.K., S.W.C., Y.J.P., K.E.L., D.W.L., S.K.P. Drafting the work or revising: K.K., S.W.C., Y.J.P., K.E.L. Final approval of the manuscript: K.K., S.W.C., Y.J.P., K.E.L., D.W.L., S.K.P.
Characteristic | Controls (n=500) | PTC (n=209) | P valuea | PTMCb (n=237) | P valuea |
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Age, yr | 47.8±11.3 | 47.7±12.4 | 0.92 | 47.6±11.6 | 0.79 |
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Body mass index, kg/m2 | 24.0±3.1 | 23.3±3.4 | 0.01 | 23.6±3.3 | 0.11 |
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Female sex | 376 (75.2) | 153 (73.2) | 0.58 | 187 (78.9) | 0.27 |
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Education (≥college) | 102 (20.4) | 111 (53.1) | <0.001 | 140 (59.1) | <0.001 |
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Ever cigarette smokers | 107 (21.4) | 44 (21.1) | 0.91 | 36 (15.2) | 0.051 |
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Ever alcohol drinkers | 258 (51.6) | 101 (48.3) | 0.43 | 131 (55.3) | 0.35 |
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Regular exercised | 203 (40.6) | 91 (43.5) | 0.47 | 90 (38.1) | 0.52 |
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Family history of cancer | 125 (25.0) | 66 (31.6) | 0.07 | 84 (35.6) | 0.003 |
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Past history of | |||||
Hypertension | 82 (16.4) | 53 (25.4) | 0.01 | 34 (14.4) | 0.47 |
Dyslipidemia | 19 (3.8) | 35 (16.8) | <0.001 | 31 (13.1) | <0.001 |
Benign thyroid disease | 14 (2.8) | 15 (7.2) | 0.01 | 23 (9.7) | <0.001 |
Diabetes | 38 (7.6) | 13 (6.2) | 0.52 | 15 (6.3) | 0.53 |
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Females only | |||||
Pregnancy | 342 (91.0) | 120 (79.5) | 0.002 | 166 (89.3) | 0.52 |
Post-menopausal | 184 (48.9) | 73 (47.7) | 0.80 | 72 (38.5) | 0.02 |
Variable | Controls (n=500) | PTC (n=209) | OR (95% CI)a | PTMCb (n=237) | OR (95% CI)a | |
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UIC, μg/gCr | ||||||
<85 | Insufficient iodine intake | 37 (7.4) | 0 | 0.25 (0.01–4.42)c | 1 (2.5) | 0.17 (0.02–1.45) |
85–219 | Adequate | 199 (39.8) | 10 (4.8) | 1.00 | 23 (9.7) | 1.00 |
≥220 | Excessive | 264 (52.8) | 199 (95.2) | 18.13 (8.87–37.04) | 213 (87.8) | 8.02 (4.64–13.87) |
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UIC, μg/L | ||||||
20–99 | Insufficient | 55 (11.0) | 3 (1.4) | 1.10 (0.25–4.76) | 2 (0.8) | 0.36 (0.07–1.76) |
100–199 | Adequate | 146 (29.2) | 6 (2.9) | 1.00 | 13 (5.5) | 1.00 |
200–299 | Above requirements | 82 (16.4) | 5 (2.4) | 1.09 (0.31–3.89) | 12 (5.1) | 1.57 (0.62–3.96) |
≥300 | Excessive | 217 (43.4) | 195 (93.3) | 20.16 (8.49–47.88) | 210 (88.6) | 10.51 (5.46–20.23) |
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UIC, μg/L | ||||||
100–299 | Adequate or above requirements | 228 (51.2) | 11 (5.3) | 1.00 | 25 (10.6) | 1.00 |
≥300 | Excessive | 217 (48.8) | 195 (94.7) | 19.45 (9.92–38.13) | 210 (89.4) | 8.76 (5.23–14.66) |
Values are expressed as number (%).
PTC, papillary thyroid cancer; PTMC, papillary thyroid microcarcinoma; OR, odds ratio; CI, confidence interval; UIC, urinary iodine concentration.
a Adjusted for age, sex, education level, family history of cancer, past history of chronic disease (dyslipidemia and benign thyroid disease), and total energy intake;
b PTMC with 5 mm≤ tumor size <10 mm;
c Logit estimation in Cochran-Mantel-Haenszel method.
Variable | Controls (n=500) | PTC (n=209) | OR (95% CI)a | PTMCb (n=237) | OR (95% CI)a |
---|---|---|---|---|---|
TSH, μIU/mL | |||||
Clinical cutpointc | |||||
<0.4 | 14 (2.8) | 7 (3.4) | 1.60 (0.59–4.34) | 10 (4.2) | 0.92 (0.33–2.60) |
0.4–4.1 | 457 (91.4) | 180 (86.1) | 1.00 | 209 (88.2) | 1.00 |
≥4.2 | 29 (5.8) | 22 (10.5) | 1.64 (0.85–3.19) | 18 (7.6) | 1.08 (0.53–2.21) |
Population cutpointc | |||||
0.4–2.15 | 337 (69.3) | 123 (60.9) | 1.00 | 136 (59.9) | 1.00 |
≥2.16 | 149 (30.7) | 79 (39.1) | 1.37 (0.93–2.01) | 91 (40.1) | 1.39 (0.95–2.05) |
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Free T4, ng/dL | |||||
Clinical cutpointc | |||||
<0.70 | 2 (0.4) | 1 (0.5) | 2.06 (0.18–23.37) | 1 (0.4) | 1.61 (0.14–18.54) |
0.70–1.80 | 494 (98.8) | 189 (90.4) | 1.00 | 216 (91.2) | 1.00 |
≥1.81 | 4 (0.8) | 19 (9.1) | 12.79 (3.98–41.18) | 20 (8.4) | 12.46 (3.71–41.88) |
Population cutpointc | |||||
0.7–1.24 | 265 (53.2) | 74 (35.6) | 1.00 | 68 (28.8) | 1.00 |
≥1.25 | 233 (46.8) | 134 (64.4) | 1.97 (1.36–2.87) | 168 (71.2) | 2.98 (2.01–4.41) |
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T3, ng/mL | |||||
Clinical cutpointc | |||||
<0.87 | 17 (3.4) | 10 (4.8) | 0.85 (0.34–2.14) | 10 (4.2) | 1.00 (0.38–2.60) |
0.87–1.84 | 479 (95.8) | 197 (94.3) | 1.00 | 224 (94.5) | 1.00 |
≥1.85 | 4 (0.8) | 2 (0.9) | 1.08 (0.17–6.74) | 3 (1.3) | 0.85 (0.15–4.82) |
Population cutpointd | |||||
0.87–1.19 | 214 (44.3) | 105 (52.8) | 1.00 | 114 (50.2) | 1.00 |
≥1.20 | 269 (55.7) | 94 (47.2) | 0.79 (0.55–1.14) | 113 (49.8) | 0.91 (0.63–1.31) |
Values are expressed as number (%).
PTC, papillary thyroid cancer; PTMC, papillary thyroid microcarcinoma; OR, odds ratio; CI, confidence interval; TSH, thyroid stimulating hormone; T4, thyroxine; T3, triiodothyronine.
a Adjusted for age, sex, education level, family history of cancer, past history of chronic disease (dyslipidemia and benign thyroid disease), and total energy intake;
b PTMC with 5 mm≤ tumor size <10 mm;
c Clinical cutpoint and population cutpoint for each thyroid hormone are referenced in the [20], and the [21] mean value based on the data from KNHANE VI (Korea National Health and Nutrition Examination Survey in 2013–2015), respectively;
d Population cutpoint of T3 (ng/mL) derived from controls.
Variable | Controls (n=463) | PTC (n=209) | OR (95% CI)a | OR (95% CI)b | PTMCc (n=236) | OR (95% CI)a | OR (95% CI)b | |
---|---|---|---|---|---|---|---|---|
UIC, μg/gCrd | Free T4, ng/dLd | |||||||
Adequate | Low | 93 | 3 | 1.00 | 1.00 | 6 | 1.00 | 1.00 |
High | 106 | 7 | 2.05 (0.51–8.14) | 2.17 (0.52–9.09) | 17 | 2.48 (0.94–6.57) | 3.14 (1.07–9.16) | |
Excessive | Low | 160 | 72 | 13.95 (4.27–45.53) | 18.06 (5.23–62.36) | 63 | 6.10 (2.54–14.65) | 7.98 (3.00–21.27) |
High | 104 | 127 | 37.86 (11.64–123.0) | 43.48 (12.63–149.62) | 150 | 19.16 (8.54–42.98) | 26.96 (10.26–70.89) | |
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UIC, μg/gCrd | TSH, μIU/mLd | |||||||
Adequate | Low | 159 | 4 | 1.00 | 1.00 | 13 | 1.00 | 1.00 |
High | 40 | 6 | 5.96 (1.60–22.13) | 4.74 (1.21–18.59) | 10 | 3.06 (0.94–6.57) | 2.48 (0.91–6.74) | |
Excessive | Low | 164 | 126 | 30.54 (11.02–84.61) | 35.16 (12.15–101.7) | 132 | 9.84 (5.34–18.12) | 10.75 (5.39–21.45) |
High | 100 | 73 | 29.02 (10.28–81.86) | 32.29 (10.88–95.81) | 81 | 9.90 (5.24–18.73) | 10.69 (5.16–22.14) |
UIC, urinary iodine concentration; PTC, papillary thyroid cancer; PTMC, papillary thyroid microcarcinoma; OR, odds ratio; CI, confidence interval; T4, thyroxine; TSH, thyroid stimulating hormone.
a Crude;
b Adjusted for age, sex, education level, family history of cancer, past history of chronic disease (dyslipidemia and benign thyroid disease), and total energy intake;
c PTMC with 5 mm≤ tumor size <10 mm;
d UIC levels were divided into two groups: ‘Adequate’ meant ‘UIC 85–219 μg/gCr,’ and ‘excessive’ meant ‘UIC ≥220 μg/gCr.’ free T4 and TSH levels were divided into two groups using population cutpoints: ‘low’ and ‘high’ free T4 levels meant ‘<1.25 ng/dL’ and ‘≥1.25 ng/dL,’ respectively; ‘low’ TSH levels meant ‘<2.16 μIU/mL’ and ‘high TSH’ ≥2.16 μIU/mL,’ respectively.