Journal Name: Breast Cancer Research and Treatment

Article Title: Risk of genome-wide association study newly identified genetic variants for breast cancer in Chinese women of Heilongjiang Province

Journal name: Breast cancer research and treatment

Authors: Yongdong Jiang1†, Jiguang Han1†, Jing Liu2, Guoqiang Zhang1, Lihong Wang3, Feng Liu1, Xianyu Zhang1, Yashuang Zhao4*, and Da Pang1,3*

Authors' Affiliations: 1Department of Breast Surgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, China; 2Department of Anesthesiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China; 3Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin, China; 4Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, China.

Corresponding author: Da Pang,

The following Additional pdf file containing a table that presents the associations of each of the seven investigated SNPs with disease characteristics and patient characteristics in women from northeast of China, Heilongjiang Province.

SNP:rs3803662 near TNCR9

Patient or disease characteristics / n / Phenotype per genotype / P, three groups† / P, two groups‡
AA / AB / BB
Genotype(number of patients) / 492 / 54 / 200 / 238
Age at diagnosis(average),years / 492 / 46.80 / 49.64 / 49.91 / 0.125 / 0.043
Age groups at diagnosis (%) / ＜40 / 492 / 25.9% / 17.0% / 14.7% / 0.508 / 0.209
40-50 / 35.2% / 34.5% / 37.8%
50-60 / 29.6% / 32.5% / 31.1%
≥60 / 9.3% / 16.0% / 16.4%
BMI(average) / 492 / 24.50 / 24.15 / 24.34 / 0.735 / 0.617
Age at menarche(average),years / 492 / 15.43 / 15.28 / 15.15 / 0.592 / 0.456
Age at menopause(average), years / 212 / 50.11 / 49.32 / 49.81 / 0.581 / 0.575
Age at first birth(average), years / 466 / 25.41 / 25.13 / 25.20 / 0.859 / 0.612
Breast feeding (%) / 492 / 81.5% / 87.5% / 86.6% / 0.517 / 0.266
Breastfeeding duration(average), months / 492 / 12.22 / 15.67 / 16.42 / 0.092 / 0.036
Parity (%) / ≥2 / 492 / 9.3% / 18.5% / 17.6% / 0.421 / 0.270
1 / 85.2% / 75.0% / 78.2%
0 / 5.6% / 6.5% / 4.2%
Abortion (%) / 0 / 492 / 44.4% / 46.5% / 50.0% / 0.533 / 0.613
1 / 25.9% / 31.5% / 25.2%
≥2 / 29.6% / 22.0% / 24.8%
Clinic stage(UICC) / 0 / 432 / 7.5% / 11.1% / 6.2% / 0.166 / 0.209
1 / 30.2% / 21.6% / 28.4%
2 / 47.2% / 60.2% / 57.2%
3-4 / 15.1% / 7.0% / 8.2%
Tumor size(cm) / ≤2 / 423 / 45.3% / 34.9% / 42.6% / 0.225 / 0.397
＞2 / 54.7% / 65.1% / 57.4%
Bloom-Richardson grade / 2 / 369 / 73.9% / 62.7% / 65.7% / 0.378 / 0.204
3 / 26.1% / 37.3% / 34.3%
LN involvement (%) / 471 / 37.7% / 46.8% / 43.5% / 0.481 / 0.317
ER positive (%) / 479 / 73.1% / 57.3% / 63.0% / 0.101 / 0.076
PR positive (%) / 479 / 67.3% / 52.1% / 53.2% / 0.133 / 0.046
HER2 positive (%) / 477 / 23.1% / 33.7% / 24.7% / 0.084 / 0.394
Ki67 positive (%) / 475 / 57.7% / 67.9% / 59.7% / 0.159 / 0.425
P53 positive (%) / 475 / 21.2% / 22.1% / 22.7% / 0.965 / 0.831
The combined status of ER,PR and HER2 / 1 / 477 / 65.4% / 50.0% / 55.7% / 0.110 / 0.266
2 / 13.5% / 12.1% / 11.9%
3 / 9.6% / 21.6% / 12.8%
4 / 11.5% / 16.3% / 19.6%

SNP:rs12443621 near TNCR9

Patient or disease characteristics / n / Phenotype per genotype / P, three groups† / P, two groups‡
AA / AB / BB
Genotype(number of patients) / 492 / 174 / 230 / 88
Age at diagnosis(average),years / 492 / 50.21 / 49.26 / 48.50 / 0.411 / 0.232
Age groups at diagnosis (%) / ＜40 / 492 / 12.6% / 17.0% / 25.0% / 0.306 / 0.261
40-50 / 36.2% / 37.0% / 34.1%
50-60 / 35.1% / 30.0% / 28.4%
≥60 / 16.1% / 16.1% / 12.5%
BMI(average) / 492 / 24.31 / 24.18 / 24.48 / 0.772 / 0.886
Age at menarche(average),years / 492 / 15.14 / 15.32 / 15.20 / 0.676 / 0.447
Age at menopause(average), years / 212 / 49.79 / 49.60 / 49.29 / 0.820 / 0.629
Age at first birth(average), years / 466 / 25.05 / 25.14 / 25.64 / 0.374 / 0.472
Breast feeding (%) / 492 / 85.1% / 88.7% / 83.0% / 0.335 / 0.526
Breastfeeding duration(average), months / 492 / 15.56 / 16.65 / 13.26 / 0.106 / 0.899
Parity (%) / ≥2 / 492 / 19.5% / 17.4% / 11.4% / 0.414 / 0.519
1 / 75.9% / 77.8% / 80.7%
0 / 4.6% / 4.8% / 8.0%
Abortion (%) / 0 / 492 / 51.1% / 47.0% / 44.3% / 0.272 / 0.575
1 / 25.9% / 26.1% / 36.4%
≥2 / 23.0% / 27.0% / 19.3%
Clinic stage(UICC) / 0 / 432 / 9.3% / 6.2% / 12.2% / 0.352 / 0.854
1 / 24.0% / 29.8% / 18.9%
2 / 58.7% / 54.3% / 62.2%
3-4 / 8.0% / 9.6% / 6.8%
Tumor size(cm) / ≤2 / 423 / 38.5% / 43.2% / 33.3% / 0.317 / 0.658
＞2 / 61.5% / 56.8% / 66.7%
Bloom-Richardson grade / 2 / 369 / 69.2% / 65.0% / 59.7% / 0.416 / 0.277
3 / 30.8% / 35.0% / 40.3%
LN involvement (%) / 471 / 41.8% / 46.3% / 43.5% / 0.667 / 0.431
ER positive (%) / 479 / 62.0% / 61.7% / 61.6% / 0.998 / 0.948
PR positive (%) / 479 / 53.8% / 53.2% / 58.1% / 0.724 / 0.876
HER2 positive (%) / 477 / 23.5% / 32.1% / 26.7% / 0.164 / 0.099
Ki67 positive (%) / 475 / 62.9% / 63.5% / 60.5% / 0.885 / 0.945
P53 positive (%) / 475 / 20.0% / 24.2% / 22.1% / 0.613 / 0.365
The combined status of ER,PR and HER2 / 1 / 477 / 58.8% / 49.8% / 58.1% / 0.329 / 0.311
2 / 8.8% / 15.8% / 9.3%
3 / 14.7% / 16.3% / 17.4%
4 / 17.6% / 18.1% / 15.1%

SNP:rs889312 in MAP3K1

Patient or disease characteristics / n / Phenotype per genotype / P, three groups† / P, two groups‡
AA / AB / BB
Genotype(number of patients) / 492 / 133 / 227 / 132
Age at diagnosis(average),years / 492 / 51.49 / 48.64 / 48.83 / 0.027 / 0.007
Age groups at diagnosis (%) / ＜40 / 492 / 12.8% / 19.4% / 16.7% / 0.439 / 0.146
40-50 / 33.1% / 36.6% / 38.6%
50-60 / 33.8% / 30.4% / 31.1%
≥60 / 20.3% / 13.7% / 13.6%
BMI(average) / 492 / 24.08 / 24.35 / 24.36 / 0.732 / 0.430
Age at menarche(average),years / 492 / 15.27 / 15.02 / 15.57 / 0.041 / 0.812
Age at menopause(average), years / 212 / 49.42 / 49.77 / 49.61 / 0.856 / 0.615
Age at first birth(average), years / 466 / 25.45 / 24.70 / 25.78 / 0.006 / 0.299
Breast feeding (%) / 492 / 87.2% / 85.5% / 87.1% / 0.859 / 0.742
Breastfeeding duration(average), months / 492 / 16.50 / 16.21 / 13.86 / 0.163 / 0.371
Parity (%) / ≥2 / 492 / 19.5% / 15.0% / 18.2% / 0.611 / 0.629
1 / 75.9% / 78.4% / 78.0%
0 / 4.5% / 6.6% / 3.8%
Abortion (%) / 0 / 492 / 51.1% / 46.3% / 47.7% / 0.703 / 0.678
1 / 25.6% / 27.3% / 31.1%
≥2 / 23.3% / 26.4% / 21.2%
Clinic stage(UICC) / 0 / 432 / 8.6% / 9.6% / 5.9% / 0.920 / 0.898
1 / 23.3% / 26.4% / 27.7%
2 / 59.5% / 55.3% / 58.0%
3-4 / 8.6% / 8.6% / 8.4%
Tumor size(cm) / ≤2 / 423 / 38.1% / 40.2% / 41.4% / 0.872 / 0.630
＞2 / 61.9% / 59.8% / 58.6%
Bloom-Richardson grade / 2 / 369 / 66.0% / 62.2% / 70.9% / 0.341 / 0.929
3 / 34.0% / 37.8% / 29.1%
LN involvement (%) / 471 / 48.0% / 40.5% / 46.8% / 0.310 / 0.304
ER positive (%) / 479 / 56.8% / 62.7% / 65.4% / 0.342 / 0.167
PR positive (%) / 479 / 47.7% / 55.0% / 59.8% / 0.141 / 0.076
HER2 positive (%) / 477 / 35.1% / 27.7% / 21.4% / 0.050 / 0.036
Ki67 positive (%) / 475 / 65.9% / 63.2% / 58.7% / 0.488 / 0.385
P53 positive (%) / 475 / 23.3% / 22.3% / 21.4% / 0.940 / 0.764
The combined status of ER,PR and HER2 / 1 / 477 / 46.6% / 55.5% / 61.1% / 0.213 / 0.084
2 / 13.0% / 13.2% / 9.5%
3 / 22.1% / 14.5% / 11.9%
4 / 18.3% / 16.8% / 17.5%

SNP:rs3817198 in LSP1

Patient or disease characteristics / n / Phenotype per genotype / P, three groups† / P, two groups‡
AA / AB / BB
Genotype(number of patients) / 492 / 366 / 122 / 4
Age at diagnosis(average),years / 492 / 49.42 / 49.52 / 51.25 / 0.937 / 0.887
Age groups at diagnosis (%) / ＜40 / 492 / 17.2% / 16.4% / 0 / 0.701 / 0.959
40-50 / 36.3% / 34.4% / 75.0%
50-60 / 30.9% / 34.4% / 0
≥60 / 15.6% / 14.8% / 25.0%
BMI(average) / 492 / 24.14 / 24.77 / 22.13 / 0.089 / 0.116
Age at menarche(average),years / 492 / 15.24 / 15.21 / 15.75 / 0.868 / 0.971
Age at menopause(average), years / 212 / 49.54 / 49.85 / 49.00 / 0.854 / 0.637
Age at first birth(average), years / 466 / 25.08 / 25.50 / 27.00 / 0.301 / 0.186
Breast feeding (%) / 492 / 87.2% / 84.4% / 75.0% / 0.372 / 0.392
Breastfeeding duration(average), months / 492 / 15.47 / 16.11 / 19.00 / 0.775 / 0.576
Parity (%) / ≥2 / 492 / 18.9% / 11.5% / 25.0% / 0.090 / 0.184
1 / 76.2% / 82.8% / 50.0%
0 / 4.9% / 5.7% / 25.0%
Abortion (%) / 0 / 492 / 50.0% / 42.6% / 25.0% / 0.426 / 0.292
1 / 27.0% / 29.5% / 50.0%
≥2 / 23.0% / 27.9% / 25.0%
Clinic stage(UICC) / 0 / 432 / 8.5% / 8.3% / 0 / 0.468 / 0.531
1 / 24.1% / 29.4% / 75.0%
2 / 58.9% / 53.2% / 25.0%
3-4 / 8.5% / 9.2% / 0
Tumor size(cm) / ≤2 / 423 / 38.1% / 43.1% / 100.0% / 0.030 / 0.189
＞2 / 61.9% / 56.9% / 0
Bloom-Richardson grade / 2 / 369 / 65.6% / 64.6% / 100.0% / 0.695 / 0.986
3 / 34.4% / 35.4% / 0
LN involvement (%) / 471 / 46.0% / 39.5% / 25.0% / 0.368 / 0.182
ER positive (%) / 479 / 61.2% / 63.2% / 75.0% / 0.909 / 0.630
PR positive (%) / 479 / 53.1% / 57.3% / 75.0% / 0.581 / 0.362
HER2 positive (%) / 477 / 31.5% / 18.8% / 0 / 0.014 / 0.005
Ki67 positive (%) / 475 / 60.3% / 71.6% / 25.0% / 0.026 / 0.057
P53 positive (%) / 475 / 22.3% / 23.3% / 0 / 0.735 / 0.955
The combined status of ER,PR and HER2 / 1 / 477 / 53.4% / 57.3% / 75.0% / 0.043 / 0.012
2 / 12.9% / 10.3% / 0
3 / 18.5% / 8.5% / 0
4 / 15.2% / 23.9% / 25.0%

SNP: rs13387042 at 2q35

Patient or disease characteristics / n / Phenotype per genotype / P, three groups† / P, two groups‡
AA / AB / BB
Genotype(number of patients) / 492 / 377 / 110 / 5
Age at diagnosis(average),years / 492 / 49.57 / 48.98 / 51.80 / 0.764 / 0.672
Age groups at diagnosis (%) / ＜40 / 492 / 17.5% / 15.5% / 0 / 0.715 / 0.439
40-50 / 34.2% / 42.7% / 40.0%
50-60 / 32.4% / 28.2% / 40.0%
≥60 / 15.9% / 13.6% / 20.0%
BMI(average) / 492 / 24.39 / 23.93 / 23.65 / 0.424 / 0.194
Age at menarche(average),years / 492 / 15.17 / 15.49 / 14.40 / 0.213 / 0.200
Age at menopause(average), years / 212 / 49.64 / 49.54 / 50.00 / 0.975 / 0.916
Age at first birth(average), years / 466 / 25.29 / 24.92 / 24.60 / 0.542 / 0.278
Breast feeding (%) / 492 / 85.1% / 90.0% / 100.0% / 0.354 / 0.148
Breastfeeding duration(average), months / 492 / 15.49 / 16.06 / 19.60 / 0.721 / 0.591
Parity (%) / ≥2 / 492 / 18.0% / 14.5% / 0 / 0.664 / 0.320
1 / 76.1% / 81.8% / 100.0%
0 / 5.8% / 3.6% / 0
Abortion (%) / 0 / 492 / 48.5% / 46.4% / 40.0% / 0.968 / 0.898
1 / 27.6% / 28.2% / 40.0%
≥2 / 23.9% / 25.5% / 20.0%
Clinic stage(UICC) / 0 / 432 / 8.1% / 9.5% / 0 / 0.830 / 0.536
1 / 25.9% / 25.3% / 40.0%
2 / 56.3% / 60.0% / 60.0%
3-4 / 9.6% / 5.3% / 0
Tumor size(cm) / ≤2 / 423 / 40.7% / 37.4% / 40.0% / 0.850 / 0.577
＞2 / 59.3% / 62.6% / 60.0%
Bloom-Richardson grade / 2 / 369 / 64.3% / 69.1% / 80.0% / 0.572 / 0.351
3 / 35.7% / 30.9% / 20.0%
LN involvement (%) / 471 / 46.5% / 35.5% / 60.0% / 0.102 / 0.065
ER positive (%) / 479 / 62.3% / 62.0% / 20.0% / 0.154 / 0.685
PR positive (%) / 479 / 53.6% / 58.3% / 20.0% / 0.206 / 0.565
HER2 positive (%) / 477 / 28.8% / 25.9% / 20.0% / 0.773 / 0.511
Ki67 positive (%) / 475 / 64.4% / 56.5% / 80.0% / 0.240 / 0.189
P53 positive (%) / 475 / 22.4% / 21.3% / 40.0% / 0.616 / 0.955
The combined status of ER,PR and HER2 / 1 / 477 / 54.4% / 56.5% / 20.0% / 0.357 / 0.781
2 / 12.9% / 10.2% / 0
3 / 15.9% / 15.7% / 20.0%
4 / 16.8% / 17.6% / 60.0%

SNP: rs13281615 at 8q24

Patient or disease characteristics / n / Phenotype per genotype / P, three groups† / P, two groups‡
AA / AB / BB
Genotype(number of patients) / 492 / 117 / 253 / 122
Age at diagnosis(average),years / 492 / 49.67 / 49.02 / 50.16 / 0.584 / 0.803
Age groups at diagnosis (%) / ＜40 / 492 / 14.5% / 18.6% / 15.6% / 0.754 / 0.854
40-50 / 36.8% / 37.5% / 32.8%
50-60 / 31.6% / 28.9% / 36.9%
≥60 / 17.1% / 15.0% / 14.8%
BMI(average) / 492 / 24.16 / 24.13 / 24.70 / 0.289 / 0.658
Age at menarche(average),years / 492 / 15.60 / 15.07 / 15.24 / 0.056 / 0.023
Age at menopause(average), years / 212 / 50.42 / 48.89 / 50.17 / 0.028 / 0.084
Age at first birth(average), years / 466 / 24.99 / 25.59 / 24.59 / 0.016 / 0.431
Breast feeding (%) / 492 / 89.7% / 85.0% / 86.1% / 0.459 / 0.225
Breastfeeding duration(average), months / 492 / 16.06 / 15.70 / 15.18 / 0.866 / 0.696
Parity (%) / ≥2 / 492 / 18.8% / 17.4% / 14.8% / 0.718 / 0.527
1 / 77.8% / 76.3% / 80.3%
0 / 3.4% / 6.3% / 4.9%
Abortion (%) / 0 / 492 / 51.3% / 45.8% / 49.2% / 0.543 / 0.544
1 / 23.9% / 28.1% / 31.1%
≥2 / 24.8% / 26.1% / 19.7%
Clinic stage(UICC) / 0 / 432 / 9.7% / 7.2% / 9.3% / 0.935 / 0.934
1 / 26.2% / 25.8% / 25.9%
2 / 56.3% / 57.0% / 58.3%
3-4 / 7.8% / 10.0% / 6.5%
Tumor size(cm) / ≤2 / 423 / 41.0% / 40.4% / 38.1% / 0.899 / 0.807
＞2 / 59.0% / 59.6% / 61.9%
Bloom-Richardson grade / 2 / 369 / 54.9% / 68.9% / 68.1% / 0.068 / 0.021
3 / 45.1% / 31.1% / 31.9%
LN involvement (%) / 471 / 46.4% / 42.7% / 44.9% / 0.795 / 0.580
ER positive (%) / 479 / 56.2% / 62.3% / 65.8% / 0.314 / 0.168
PR positive (%) / 479 / 52.7% / 53.0% / 58.3% / 0.587 / 0.698
HER2 positive (%) / 477 / 27.9% / 28.5% / 27.5% / 0.981 / 0.965
Ki67 positive (%) / 475 / 66.7% / 58.0% / 68.9% / 0.080 / 0.328
P53 positive (%) / 475 / 23.4% / 23.7% / 18.5% / 0.510 / 0.749
The combined status of ER,PR and HER2 / 1 / 477 / 53.2% / 55.3% / 54.2% / 0.406 / 0.155
2 / 7.2% / 13.0% / 15.0%
3 / 20.7% / 15.4% / 12.5%
4 / 18.9% / 16.3% / 18.3%

SNP: rs2046210 at 6q25

Patient or disease characteristics / n / Phenotype per genotype / P, three groups† / P, two groups‡
AA / AB / BB
Genotype(number of patients) / 492 / 171 / 235 / 86
Age at diagnosis(average),years / 492 / 49.02 / 49.71 / 49.65 / 0.789 / 0.492
Age groups at diagnosis (%) / ＜40 / 492 / 18.7% / 14.5% / 19.8% / 0.479 / 0.640
40-50 / 34.5% / 39.1% / 31.4%
50-60 / 33.3% / 31.5% / 27.9%
≥60 / 13.5% / 14.9% / 20.9%
BMI(average) / 492 / 24.18 / 24.21 / 24.67 / 0.493 / 0. 639
Age at menarche(average),years / 492 / 15.09 / 15.35 / 15.21 / 0.409 / 0.227
Age at menopause(average), years / 212 / 48.46 / 50.22 / 50.23 / 0.006 / 0.001
Age at first birth(average), years / 466 / 25.10 / 25.27 / 25.17 / 0.873 / 0.649
Breast feeding (%) / 492 / 84.8% / 89.8% / 80.2% / 0.066 / 0.454
Breastfeeding duration(average), months / 492 / 15.34 / 16.40 / 14.26 / 0.381 / 0.688
Parity (%) / ≥2 / 492 / 16.4% / 17.4% / 17.4% / 0.996 / 0.955
1 / 78.4% / 77.0% / 77.9%
0 / 5.3% / 5.5% / 4.7%
Abortion (%) / 0 / 492 / 55.6% / 44.3% / 43.0% / 0.132 / 0.033
1 / 25.7% / 29.4% / 27.9%
≥2 / 18.7% / 26.4% / 29.1%
Clinic stage(UICC) / 0 / 432 / 8.7% / 7.8% / 9.1% / 0.958 / 0.814
1 / 28.2% / 24.3% / 26.0%
2 / 55.7% / 59.2% / 54.5%
3-4 / 7.4% / 8.7% / 10.4%
Tumor size(cm) / ≤2 / 423 / 46.2% / 35.1% / 40.8% / 0.115 / 0.058
＞2 / 53.8% / 64.9% / 59.2%
Bloom-Richardson grade / 2 / 369 / 66.1% / 68.0% / 58.6% / 0.369 / 0.880
3 / 33.9% / 32.0% / 41.4%
LN involvement (%) / 471 / 47.0% / 42.4% / 43.4% / 0.665 / 0.373
ER positive (%) / 479 / 63.3% / 60.1% / 63.5% / 0.764 / 0.633
PR positive (%) / 479 / 54.8% / 53.9% / 54.1% / 0.985 / 0.863
HER2 positive (%) / 477 / 29.7% / 27.3% / 27.1% / 0.851 / 0.571
Ki67 positive (%) / 475 / 64.0% / 61.2% / 64.3% / 0.810 / 0.673
P53 positive (%) / 475 / 21.3% / 23.8% / 20.2% / 0.747 / 0.711
The combined status of ER,PR and HER2 / 1 / 477 / 57.0% / 53.7% / 51.8% / 0.536 / 0.376
2 / 12.1% / 11.0% / 15.3%
3 / 17.6% / 16.3% / 11.8%
4 / 13.3% / 18.9% / 21.2%

Note: LN: lymph node, ER: estrogen receptor, PR: progesterone receptor, HER2: human epidermal growth factor receptor2.