Background
Methods
Case and control selection
Collection of questionnaire data and blood specimens
Measurement of plasma levels of Hcy
Genotyping of the SHMT C1420T, CBS C699T/C1080T, MS A2756G, MTRR A66G polymorphisms determination
Statistical analysis
Results and discussion
Characteristics of case and controls
Cases (n = 96) n (%) | Controls (n = 85) n (%) |
p
| |
---|---|---|---|
Age | |||
18–29 | 12(12.5) | 9(17.6) | |
30–39 | 25(26.0) | 22(25.9) | |
40–49 | 37(38.5) | 37(43.5) | |
50–59 | 14(14.6) | 13(15.3) | |
60–69 | 4(4.17) | 3(3.53) | |
70–79 | 4(4.17) | 1(1.18) | |
Mean age (SD) | 47.83(±10.9) | 45.22(±11.8) | 0.37 |
Drinking habit | |||
Never | 83(89.6) | 81(95.3) | |
Formera
| 6(6.25) | 0(0) | |
Current | 4(4.17) | 1(1.18) | |
Moderateb
| 2(2.08) | 1(1.18) | 0.21 |
Heavyc
| 1(1.04) | 0(0) | |
Unknown | 0(0) | 3(3.53) | |
Somking habit | |||
Never | 76(79.2) | 85(100) | <0.01 |
Formera
| 14(14.6) | 0(0) | <0.01 |
Current (pack years) | 6(6.25) | 0(0) | |
0–19 | 2(2.08) | 0(0) | |
≥20 | 3(3.12) | 0(0) | |
Unknown | 1(1.04) | 0 | |
BMI | |||
<18.5 | 9(9.38) | 7(8.24) | |
18.5–24.9 | 30(31.3) | 26(30.6) | |
≥25.0 | 53(55.2) | 50(58.8) | |
Unknown | 4(4.17) | 2(2.35) | 0.87 |
Regular exercise | |||
Yes | 62(64.6) | 63(74.1) | |
No | 29(30.2) | 21(21.9) | |
Unknown | 5(5.21) | 1(1.04) | 0.11 |
Family history of breast cancer | |||
Yes | 0(0) | 0(0) | |
No | 96(100) | 85(100) | |
Unknown | 0(100) | 0(100) | 1.00 |
Menopausal status | |||
Premenopausal | 69(71.9) | 64(75.3) | |
Postmenopausal | 27(28.1) | 21(24.7) | 0.74 |
Age at menarche | |||
≤12 | 24(25) | 19(22.4) | |
13–14 | 66(68.8) | 60(70.6) | |
≥15 | 2(2.08) | 44.70) | |
Unknown | 4(4.16) | 2(2.35) | 0.82 |
Age at menopause | |||
≤47 | 4(4.17) | 2(2.35) | |
48–52 | 13(13.5) | 10(11.8) | |
≥53 | 9(9.38) | 7(8.24) | |
Unknown | 1(1.04) | 2(2.35) | 0.91 |
Others | 2(2.08) | 1(1.17) | 0.21 |
Effect of plasma Hcy levels on risk of breast cancer
Variablea,b
| Cases (n = 96) n (%) | Controls (n = 85) n (%) | ORc(95% CIc) |
---|---|---|---|
Plasma total Hcy(μ mol/L) | |||
<7.26 | 16(16.7) | 28(32.9) | 1.00(reference) |
7.26–11.56 | 11(11.4) | 30(35.3) | 0.64(0.23–1.12) |
>11.56 | 69(71.9) | 27(31.8) | 4.45(1.89–6.24) |
Stratified variablea,b
| Plasma total Hcy (μ mol/L) | |||
---|---|---|---|---|
1st | 2nd | 3rd |
p
| |
Menopausal status | ||||
Pre-menopausal | <0.001 | |||
Cases/controls | 8/20 | 4/19 | 57/25 | |
ORc (95% CIc) | 1.0(reference) | 0.53(0.2-1.1) | 5.7(2.7-8.8) | |
Post-menopausal | <0.001 | |||
Cases/controls | 8/8 | 7/11 | 12/2 | |
ORc (95% CIc) | 1.0(reference) | 0.64(0.2-1.5) | 6(3.1-8.2) |
Analysis of gene polymorphisms and risk of breast cancer
Genotype
| Cases (n = 96) n (%) | Controls (n = 85) n (%) | Mutation Allelic frequency |
p
a
| |
---|---|---|---|---|---|
Cases (%) | Controls (%) | ||||
SHMT C1420T
| 96(100.0) | 85(100.0) | 29.7 | 41.2 | 0.039*
|
CC
| 48(50.0) | 32(37.6) | |||
CT
| 39(40.6) | 36(42.4) | |||
TT
| 9(9.4) | 17(20) | |||
CBS C699T
| 96(100.0) | 85(100.0) | 37.5 | 35.9 | 0.962 |
CC
| 38(39.6) | 36(42.4) | |||
CT
| 44(45.8) | 37(43.5) | |||
TT
| 14(14.6) | 12(14.1) | |||
CBS C1080T
| 96(100.0) | 85(100.0) | 32.3 | 37.6 | 0.624 |
CC
| 47(49.0) | 34(40.0) | |||
CT
| 36(37.5) | 38(44.7) | |||
TT
| 13(13.5) | 13(15.3) | |||
MS A2756G
| 96(100.0) | 85(100.0) | 20.3 | 11.1 | 0.004**
|
AA
| 59(61.4) | 69(81.2) | |||
AG
| 35(36.4) | 13(15.3) | |||
GG
| 2(2.2) | 3(3.5) | |||
MTRR A66G
| 96(100.0) | 85(100.0) | 45.3 | 25.9 | 0.007**
|
AA
| 13(13.5) | 9(10.6) | |||
AG
| 79(82.3) | 75(88.2) | |||
GG
| 4(0.04) | 1(0.12) |
Genotype | Cases n (%) | Controls n (%) | ORa(95% CIa) |
p
b
|
---|---|---|---|---|
SHMT 1420CC
| 48(50.0) | 32(37.6) | 1.0 (Reference) | |
SHMT 1420CT
| 39(40.6) | 36(42.4) | 0.828(0.54 to 1.27) | 0.388 |
SHMT 1420TT
| 9(9.40) | 17(20) | 0.422(0.40 to 1.71) | 0.021*
|
SHMT 1420CT/TT
| 48(50.0) | 53(62.4) | 0.527(0.55 to 1.24) | 0.036*
|
CBS 699CC
| 38(39.6) | 36(42.4) | 1.0 (Reference) | |
CBS 699CT
| 44(45.8) | 37(43.5) | 1.10(0.66 to 2.54) | 0.69 |
CBS 699TT
| 14(14.6) | 12(14.1) | 1.14(0.38 to 1.83) | 0.73 |
CBS 699CT/TT
| 58(60.4) | 49(57.6) | 1.27(0.45 to 1.65) | 0.82 |
CBS 1080CC
| 47(49.0) | 34(40.0) | 1.0 (Reference) | |
CBS 1080CT
| 36(37.5) | 38(44.7) | 1.0 (Reference) | 0.86 |
CBS 1080TT
| 13(13.5) | 13(15.3) | 1.04(0.42 to 2.27) | 0.90 |
CBS 1080CT/TT
| 49(51.0) | 51(60) | 1.15(0.69 to 3.11) | 0.85 |
MS 2756AA
| 59(61.4) | 61(71.8) | 1.0 (Reference) | |
MS 2756AG
| 35(36.4) | 21(24.7) | 2.49(0.29 to 0.833) | 0.009**
|
MS 2756GG
| 2(2.2) | 3(3.5) | 1.72(0.13 to 2.11) | 0.36 |
MS 2756AG/GG
| 37(38.5) | 24(28.2) | 2.32(0.29 to 0.82) | 0.006**
|
MTRR 66AA
| 13(13.5) | 9(10.6) | 1.0 (Reference) | |
MTRR 66AG
| 79(82.3) | 75(88.2) | 1.17(0.26 to 2.23) | 0.51 |
MTRR 66GG
| 4(4.17) | 1(1.18) | 2.61(0.30 to 1.18) | 0.03*
|
MTRR 66AG/GG
| 83(86.5) | 76(89.4) | 1.84(0.25 to 1.66) | 0.047*
|
Hcy levels in different gene polymorphisms
Genotype | Plasma total Hcy(μ mol/L)a
|
p
b
| |
---|---|---|---|
Cases | Controls | ||
SHMT 1420CC
| 16.44 ± 17.69 | 14.99 ± 7.12 | 0.15 |
SHMT 1420CT
| 18.74 ± 12.32 | 11.04 ± 4.64 | 0.01**
|
SHMT 1420TT
| 14.86 ± 6.06 | 10.02 ± 2.97 | 0.014*
|
p = 0.021*(TT&CC) | p = 0.033*(TT&CC) | ||
CBS 699CC
| 14.47 ± 3.32 | 10.36 ± 5.12 | 0.01**
|
CBS 699CT
| 21.62 ± 13.08 | 11.20 ± 3.56 | 0.011*
|
CBS 699TT
| 19.52 ± 15.89 | 15.47 ± 6.82 | 0.019*
|
p = 0.01**(TT&CC) | p = 0.028**(TT&CC) | ||
CBS 1080CC
| 15.76 ± 7.17 | 9.28 ± 3.30 | 0.01**
|
CBS 1080CT
| 16.64 ± 10.95 | 11.67 ± 2.36 | 0.021*
|
CBS 1080TT
| 20.99 ± 16.89 | 16.45 ± 9.45 | 0.01**
|
p = 0.01**(TT&CC) | p = 0.01**(TT&CC) | ||
MS 2756AA
| 12.23 ± 5.16 | 10.71 ± 3.30 | 0.121 |
MS 2756AG
| 20.43 ± 15.32 | 13.39 ± 7.91 | 0.01**
|
MS 2756GG
| 21.15 ± 23.30 | 19.97 ± 12.88 | 0.042*
|
p = 0.01**(GG&AA) | p = 0.002**(GG&AA) | ||
MTRR 66AA
| 17.52 ± 5.69 | 10.88 ± 2.67 | 0.01**
|
MTRR 66AG
| 15.83 ± 10.99 | 12.67 ± 5.13 | 0.040*
|
MTRR 66GG
| 23.70 ± 23.51 | 22.20 | |
p = 0.031*(GG&AA) |