Genetic Variants Associated with Thyroid Cancer Risk: Comprehensive Research Synopsis, Meta-Analysis, and Cumulative Epidemiological Evidence

Table 1

Statistically significant variants from meta-analysis, false-positive report probabilities (FPRPs), and cumulative epidemiological evidence.

Gene

Variant

Alleles

Ethnicity

MAF†

Studies

Number evaluation

Risk of meta-analysis

PQ

Amount of evidence

Replication

Protection from bias

Reason for bias exemption

Venice criteria grade§

FPRP values at prior probability of 0.05 and OR of 1.5

Cumulative epidemiological evidence^¶

Sample size (case/control)

Genetic models

Effect model

OR (95% CI)

value

I (%)

N‡minor

Grade

Grade

Pegger

POU5F1B

rs6983267

G > T

Overall

0.47

10

30673 (7504/23169)

Allelic

F

1.129 (1.086 − 1.174)

≤0.01

28.1

0.19

29188

A

B

C^a

0.25

No

ABC

≤0.01

Moderate

9

27428 (7018/20410)

Dominant

F

1.175 (1.107 − 1.247)

≤0.01

0.0

0.48

20223

A

A

A

0.33

No

AAA

≤0.01

Strong

9

27428 (7018/20410)

Recessive

F

1.158 (1.091 − 1.228)

≤0.01

27.6

0.19

6725

A

B

A

0.28

No

ABA

≤0.01

Strong

miR-146a

rs2910164

G > C

Overall

0.32

12

16737 (4857/11880)

Dominant

R

1.144 (1.003 − 1.304)

≤0.01

57.0

≤0.01

8639

A

C

C^a

0.89

No

ACC

0.46

Weak

FOXE1

rs71369530

>14-Ala vs. ≤14-Ala

Caucasian

0.24

4

1271 (576/695)

Allelic

R

1.836 (1.353 − 2.492)

≤0.01

64.5

0.04

757

B

C

A

0.27

No

BCA

0.02

Moderate

FOXE1

rs907580

C > T

Caucasian

0.26

3

6884 (497/6387)

Allelic

R

1.593 (1.184 − 2.145)

≤0.01

67.6

0.05

3733

A

C

A

0.80

No

ACA

0.11

Weak

NKX2-1

rs944289

C > T

Overall

0.55

17

65182 (9467/55715)

Allelic

F

1.304 (1.255 − 1.355)

≤0.01

45.5

0.02

72278

A

B

A

0.40

No

ABA

≤0.01

Strong

10

16277 (5187/11090)

Dominant

F

1.609 (1.465 − 1.767)

≤0.01

26.3

0.20

12706

A

B

A

0.24

No

ABA

≤0.01

Strong

10

16277 (5187/11090)

Recessive

F

1.414 (1.301 − 1.536)

≤0.01

40.5

0.09

5073

A

B

A

0.14

No

ABA

≤0.01

Strong

FOXE1

rs965513

G > A

Overall

0.34

18

61943 (8167/53776)

Allelic

R

1.703 (1.575 − 1.842)

≤0.01

66.7

≤0.01

43701

A

C

A

0.13

No

ACA

≤0.01

Moderate

9

14348 (3680/10668)

Dominant

R

1.694 (1.429 − 2.010)

≤0.01

68.4

≤0.01

7542

A

C

A

0.17

No

ACA

≤0.01

Moderate

9

14348 (3680/10668)

Recessive

F

1.954 (1.729 − 2.208)

≤0.01

46.4

0.06

1599

A

B

C^d

0.02

No

ABC

≤0.01

Moderate

DIRC3

rs966423

T > C

Overall

0.50

5

9604 (4953/4651)

Allelic

F

1.227 (1.153 − 1.306)

≤0.01

0.0

0.44

9931

A

A

A

0.13

No

AAA

≤0.01

Strong

FOXE1

rs1443434

T > G

Caucasian

0.39

4

9627 (2453/7174)

Allelic

R

1.392 (1.084 − 1.787)

≤0.01

78.7

≤0.01

7800

A

C

A

0.54

No

ACA

0.20

Weak

FOXE1

rs1867277

G > A

Caucasian

0.39

12

21820 (5654/16166)

Allelic

F

1.503 (1.426 − 1.583)

≤0.01

43.7

0.05

18169

A

B

A

0.47

No

ABA

≤0.01

Strong

6

10702 (2958/7744)

Dominant

R

1.702 (1.352 − 2.143)

≤0.01

65.4

≤0.01

6892

A

C

A

0.21

No

ACA

≤0.01

Moderate

6

10702 (2958/7744)

Recessive

F

1.703 (1.498 − 1.937)

≤0.01

44.4

0.11

1809

A

B

A

0.20

No

ABA

≤0.01

Strong

FOXE1

rs2439302

C > G

Overall

0.35

4

9265 (3146/6119)

Allelic

F

1.325 (1.240 − 1.415)

≤0.01

25.6

0.26

7409

A

B

A

0.42

No

ABA

≤0.01

Strong

FOXE1

rs30215269

T > C

Caucasian

0.39

3

6997 (684/6313)

Allelic

R

1.634 (1.254 − 2.127)

≤0.01

62.0

0.07

5555

A

C

A

0.99

No

ACA

0.97

Weak

MTHFR C677T

rs1801133

C > T

Overall

0.30

8

6267 (2902/3365)

Allelic

R

1.418 (1.114 − 1.806)

≤0.01

71.4

≤0.01

4276

A

C

A

0.39

No

ACA

0.12

Weak

9

7454 (3447/4007)

Dominant

R

1.383 (1.081 − 1.769)

≤0.01

69.0

≤0.01

4337

A

C

A

0.31

No

ACA

0.20

Weak

8

6267 (2902/3365)

Recessive

F

1.258 (1.081 − 1.464)

≤0.01

43.1

0.09

843

B

B

A

0.95

No

BBA

0.06

Moderate

RET A45A

rs1800858

G > A

Overall

0.31

8

4620 (1867/2753)

Allelic

F

0.898 (0.818 − 0.987)

0.03

18.9

0.28

2885

A

A

C^ab

0.24

No

AAC

0.33

Weak

7

4462 (1809/2653)

Dominant

F

0.867 (0.764 − 0.984)

0.03

11.0

0.35

2358

A

A

C^b

0.55

No

AAC

0.34

Weak

RET G691S

rs1799939

G > A

Overall

0.21

12

6643 (2853/3790)

Allelic

R

1.352 (1.171 − 1.561)

≤0.01

53.8

≤0.01

2934

A

C

A

0.12

No

ACA

≤0.01

Moderate

12

6643 (2853/3790)

Dominant

R

1.386 (1.155 − 1.664)

≤0.01

55.6

≤0.01

2475

A

C

A

0.63

No

ACA

≤0.01

Moderate

12

6643 (2853/3790)

Recessive

R

1.535 (1.224 − 1.924)

≤0.01

0.0

0.90

459

B

A

A

0.29

No

BAA

≤0.01

Strong

RET S836S

rs1800862

C > T

Caucasian

0.04

14

6654 (2701/3953)

Allelic

F

1.129 (1.008 − 1.409)

0.04

21.8

0.22

637

B

B

C^ab

0.74

No

BBC

0.88

Weak

9

5791 (2250/3541)

Dominant

F

1.283 (1.058 − 1.557)

≤0.01

36.6

0.13

500

B

B

C^d

≤0.01

No

BBC

0.19

Weak

RET S904S

rs1800863

C > G

Overall

0.19

6

3073 (1178/1895)

Recessive

F

1.578 (1.090 − 2.286)

0.02

0.0

0.75

124

B

A

A

0.48

No

BAA

0.43

Weak

TERT

rs2736100

T > G

Asian

0.39

5

10104 (5052/5052)

Allelic

F

1.430 (1.352 − 1.512)

≤0.01

22.6

0.27

8802

A

B

A

0.49

No

ABA

≤0.01

Strong

5

10104 (5052/5052)

Dominant

F

1.535 (1.411 − 1.668)

≤0.01

15.5

0.32

6768

A

A

A

0.95

No

AAA

≤0.01

Strong

5

10104 (5052/5052)

Recessive

F

1.666 (1.509 − 1.839)

≤0.01

0.0

0.72

2034

A

A

A

0.64

No

AAA

≤0.01

Strong

XRCC3 A17893G

rs1799794

A > G

Overall

0.29

4

2477 (1106/1371)

Allelic

R

1.275 (1.008 − 1.613)

0.04

71.2

0.02

1519

A

C

C^c

0.33

No

ACC

0.47

Weak

4

2477 (1106/1371)

Dominant

R

1.321 (1.023 − 1.705)

0.03

55.4

0.08

1184

A

C

C^c

0.73

No

ACC

0.43

Weak

4

2477 (1106/1371)

Recessive

F

1.383 (1.092 − 1.750)

≤0.01

29.8

0.23

335

B

B

C^c

0.74

No

BBC

0.15

Weak

XRCC3

rs861539

C > T

Overall

0.24

11

5978 (2413/3565)

Allelic

R

1.363 (1.193 − 1.559)

≤0.01

53.9

0.02

3142

A

C

C^d

0.03

No

ACC

≤0.01

Moderate

11

5978 (2413/3565)

Dominant

R

1.357 (1.135 − 1.622)

≤0.01

56.9

≤0.01

2570

A

C

A

0.35

No

ACA

0.62

Weak

11

5978 (2413/3565)

Recessive

F

1.709 (1.428 − 2.046)

≤0.01

19.6

0.26

572

B

A

C^d

≤0.01

No

BAC

≤0.01

Moderate

F: meta-analysis was performed under the fixed-effects model. R: meta-analysis was performed under the random-effects model. Overall: two or more ethnicities were reported in the study. †Frequency of minor allele in controls. ‡Number of test allele or genotype. §Venice criteria grades are amount of evidence, replication of the association, and protection from bias. ^¶Cumulative epidemiological evidence as graded by the combination of results from the Venice criteria and FPRP. ^aThe grade of C is given because the OR value is between 0.87 and 1.15, and the association is not replicated by GWAS or GWAS meta-analysis. ^bThe grade of C is given for no significant association existed by excluding the first published study. ^cThe grade of C is given for no significant association existed by excluding studies deviated from the HWE in the controls. ^dThe grade of C is given for significant publication bias (Pegger ≤0.05)