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

Table 2

Significant variants in subtype analysis 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

Caucasian

0.50

7

47420 (11450/35970)

Allelic

F

1.139 (1.090 − 1.190)

≤0.01

31.2

0.19

24106

A

B

C^a

0.32

No

ABC

≤0.01

Moderate

Caucasian

7

23710 (5725/17985)

Dominant

F

1.202 (1.117 − 1.294)

≤0.01

0.0

0.65

17952

A

A

A

0.29

No

AAA

≤0.01

Strong

Caucasian

7

23710 (5725/17985)

Recessive

F

1.177 (1.097 − 1.261)

≤0.01

45.3

0.09

6154

A

B

A

0.31

No

ABA

≤0.01

Strong

Asian

0.35

3

13926 (3558/10368)

Allelic

F

1.095 (1.009 − 1.189)

0.03

36.3

0.21

5082

A

B

C^a

0.23

No

ABC

0.37

Weak

Asian

2

3718 (1293/2425)

Dominant

F

1.123 (1.015 − 1.242)

0.02

38.5

0.20

2271

A

B

C^a

0.20

No

ABC

0.31

Weak

NKX2-1

rs944289

C > T

Caucasian

0.56

13

59074 (7732/51342)

Allelic

F

1.273 (1.220 − 1.329)

≤0.01

31.1

0.13

66909

A

B

A

0.96

No

ABA

≤0.01

Strong

Caucasian

7

13356 (3957/9399)

Dominant

F

1.468 (1.311 − 1.644)

≤0.01

0.0

0.72

10675

A

A

A

0.45

No

AAA

≤0.01

Strong

Caucasian

7

13356 (3957/9399)

Recessive

F

1.378 (1.255 − 1.514)

≤0.01

47.2

0.08

4399

A

B

A

0.34

No

ABA

≤0.01

Strong

Asian

0.41

4

6108 (1735/4373)

Allelic

F

1.429 (1.315 − 1.553)

≤0.01

50.2

0.11

5369

A

C

A

0.97

No

ACA

≤0.01

Moderate

Asian

3

2921 (1230/1691)

Dominant

F

1.968 (1.663 − 2.328)

≤0.01

0.0

0.80

2031

A

A

A

0.82

No

AAA

≤0.01

Strong

Asian

3

2921 (1230/1691)

Recessive

F

1.544 (1.296 − 1.840)

≤0.01

19.0

0.29

674

B

A

A

0.25

No

BAA

≤0.01

Strong

FOXE1

rs965513

G > A

Caucasian

0.35

16

59202 (7025/52177)

Allelic

R

1.747 (1.613 − 1.891)

≤0.01

64.1

≤0.01

42714

A

C

A

0.54

No

ACA

≤0.01

Moderate

Caucasian

7

11607 (2538/9069)

Dominant

R

1.765 (1.437 − 2.168)

≤0.01

69.6

≤0.01

6683

A

C

A

0.16

No

ACA

≤0.01

Moderate

Caucasian

7

11607 (2538/9069)

Recessive

F

2.027 (1.780 − 2.307)

≤0.01

49.8

0.06

1471

A

B

A

0.05

No

ABA

≤0.01

Strong

DIRC3

rs966423

T > C

Caucasian

0.42

4

7794 (4108/3686)

Allelic

F

1.214 (1.135 − 1.298)

≤0.01

0.8

0.39

6979

A

A

A

0.12

No

AAA

≤0.01

Strong

FOXE1

rs966423

T > C

Caucasian

0.42

4

7794 (4108/3686)

Allelic

F

1.214 (1.135 − 1.298)

≤0.01

0.8

0.39

6979

A

A

A

0.12

No

AAA

≤0.01

Strong

FOXE1

rs2439302

C > G

Caucasian

0.48

3

6006 (2611/3395)

Allelic

F

1.326 (1.233 − 1.426)

≤0.01

50.4

0.13

6088

A

C

A

0.05

No

ACA

≤0.01

Moderate

MTHFR C677T

rs1801133

C > T

Caucasian

0.23

5

1728 (514/1214)

Allelic

R

1.434 (1.148 − 1.791)

≤0.01

36.5

0.18

897

B

B

A

0.24

No

BBA

0.04

Strong

Caucasian

5

1728 (514/1214)

Dominant

R

1.423 (1.024 − 1.977)

0.04

50.3

0.09

771

B

C

A

0.43

No

BCA

0.52

Weak

Caucasian

5

1728 (514/1214)

Recessive

F

2.279 (1.545 − 3.363)

≤0.01

0.0

0.89

126

B

A

A

0.70

No

BAA

0.04

Strong

RET A45A

rs1800858

G > A

Caucasian

0.28

6

3808 (1440/2368)

Allelic

F

0.895 (0.804 − 0.997)

0.04

0.0

0.45

2134

A

A

C^ab

0.69

No

AAC

0.46

Weak

Caucasian

5

3650 (1382/2268)

Dominant

F

0.857 (0.746 − 0.985)

0.03

19.2

0.29

1782

A

A

C^b

0.49

No

AAC

0.36

Weak

RET G691S

rs1799939

G > A

Caucasian

0.22

8

4971 (1992/2979)

Allelic

R

1.322 (1.103 − 1.584)

≤0.01

60.0

≤0.01

2371

A

C

A

0.24

No

ACA

0.05

Moderate

Caucasian

8

4971 (1992/2979)

Dominant

R

1.356 (1.060 − 1.736)

0.02

64.3

≤0.01

1979

A

C

A

0.55

No

ACA

0.27

Weak

Caucasian

8

4971 (1992/2979)

Recessive

R

1.437 (1.117 − 1.849)

≤0.01

0.0

0.91

392

B

A

A

0.65

No

BAA

0.13

Moderate

Asian

0.15

4

1672 (861/811)

Allelic

R

1.426 (1.116 − 1.822)

≤0.01

40.5

0.17

563

B

B

A

0.12

No

BBA

0.12

Moderate

Asian

4

1672 (861/811)

Dominant

R

1.444 (1.098 − 1.899)

≤0.01

34.5

0.21

496

B

B

A

0.25

No

BBA

0.21

Weak

Asian

4

1672 (861/811)

Recessive

R

2.002 (1.192 − 3.362)

≤0.01

0.0

0.61

67

C

A

C^d

≤0.01

No

CAC

0.55

Weak

XRCC1

rs1799782

C > T

Asian

0.24

5

3388 (1404/1984)

Recessive

R

1.777 (1.245 − 2.537)

≤0.01

53.7

0.07

321

B

C

C^d

0.93

No

BCC

0.14

Weak

XRCC3

rs861539

C > T

Caucasian

0.31

6

2611 (1029/1582)

Allelic

R

1.252 (1.060 − 1.478)

≤0.01

37.8

0.15

1641

A

B

A

0.12

No

ABA

0.13

Moderate

Caucasian

6

2611 (1029/1582)

Recessive

F

1.427 (1.114 − 1.826)

≤0.01

0.0

0.42

321

B

A

C^d

0.02

No

BAC

0.12

Weak

Asian

0.19

5

3367 (1384/1983)

Allelic

R

1.507 (1.256 − 1.808)

≤0.01

51.8

0.08

1501

A

C

A

0.78

No

ACA

≤0.01

Moderate

Asian

5

3367 (1384/1983)

Dominant

R

1.485 (1.178 − 1.871)

≤0.01

54.3

0.68

1250

A

C

A

0.31

No

ACA

0.03

Moderate

Asian

5

3367 (1384/1983)

Recessive

F

2.103 (1.614 − 2.739)

≤0.01

0.0

0.54

251

B

A

A

0.28

No

BAA

≤0.01

Strong

F: meta-analysis was performed under the fixed-effects model. R: meta-analysis was performed under the random-effects model. †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. ^dThe grade of C is given for significant publication bias (Pegger ≤0.05)