Novel Shared Heritable Candidate Risk Loci of Breast and Endometrial Cancer—A Swedish Haplotype Genome-Wide Association Study
· 2025-06-06
Breast and endometrial cancer are prevalent and share both hormonal and environmental risk factors. This study aimed to identify shared germline genetic risk loci for these cancers. In total, 1116 endometrial cancer cases, 3200 breast cancer cases, and 5021 healthy controls were included in a merged sliding window haplotype genome-wide association study (GWAS). This analysis employed a logistic regression model in PLINK v1.07. The results from this merged analysis were compared with previous individual analyses of the same samples. The analysis identified three loci that influenced both the risk of breast and endometrial cancer: 8p21.1 (OR 2.1; p 1.6 × 10−8), 16q24.3 (OR 2.4; p 3.8 × 10−8) and 17q11.2 (OR 1.3; p 4.3 × 10−8). This combined haplotype GWAS of endometrial and breast cancers identified three loci associated with shared genetic risk, two of which were novel: 16q24.3 and 17q11.2. Further studies are warranted to replicate these findings and to determine its pathophysiological role and future clinical implications.
Funding
CIHR
MOP-86727
National Health and Medical Research Council
1109286
National Health and Medical Research Council
ID1111246
US National Institutes of Health
CA1X01HG007491-01
US National Institutes of Health
U19-CA148112
Märit and Hans Rausing´s initiative against Breast cancer
Stockholm County Council
500395
NCI NIH HHS
U19 CA148112
NCI NIH HHS
R01 CA149429
NCI NIH HHS
U19 CA148065
Swedish Cancer Society
18-0700
National Health and Medical Research Council
ID1173170
National Institute of Health U19
CA148065
Ovarian Cancer Research Fund
268201200008I
NCI NIH HHS
R01 CA058598
Swedish Research Council
2019-01441
US National Institutes of Health
R01-CA149429
National Health and Medical Research Council
1031333
Cancer UK Grant
C1287
The Cancer Research Funds of Radiumhemmet
191203
Cancer UK Grant
A16563
European Community's Seventh Framework Programme
223175
Genome Canada Grant
GPH-129344
US National Institutes of Health
R01-CA058598
Swedish Cancer Society
2019-01441
Swedish Cancer Society
191203
Swedish Cancer Society
500395
Swedish Cancer Society
223175 (HEALTH-F2-2009-223175)
Swedish Cancer Society
1031333
Swedish Cancer Society
1109286
Swedish Cancer Society
CA1X01HG007491-01
Swedish Cancer Society
U19-CA148112
Swedish Cancer Society
R01-CA149429
Swedish Cancer Society
R01-CA058598
Swedish Cancer Society
MOP-86727
Swedish Cancer Society
GPH-129344
Swedish Cancer Society
U19 CA148065
Swedish Cancer Society
C1287/A16563
Swedish Cancer Society
1111246
Swedish Cancer Society
1173170
Swedish Research Council
18-0700
Swedish Research Council
191203
Swedish Research Council
500395
Swedish Research Council
223175 (HEALTH-F2-2009-223175)
Swedish Research Council
1031333
Swedish Research Council
1109286
Swedish Research Council
CA1X01HG007491-01
Swedish Research Council
U19-CA148112
Swedish Research Council
R01-CA149429
Swedish Research Council
R01-CA058598
Swedish Research Council
MOP-86727
Swedish Research Council
GPH-129344
Swedish Research Council
U19 CA148065
Swedish Research Council
C1287/A16563
Swedish Research Council
1111246
Swedish Research Council
1173170
The Cancer Research Funds of Radiumhemmet
18-0700
The Cancer Research Funds of Radiumhemmet
2019-01441
The Cancer Research Funds of Radiumhemmet
500395
The Cancer Research Funds of Radiumhemmet
223175 (HEALTH-F2-2009-223175)
The Cancer Research Funds of Radiumhemmet
1031333
The Cancer Research Funds of Radiumhemmet
1109286
The Cancer Research Funds of Radiumhemmet
CA1X01HG007491-01
The Cancer Research Funds of Radiumhemmet
U19-CA148112
The Cancer Research Funds of Radiumhemmet
R01-CA149429
The Cancer Research Funds of Radiumhemmet
R01-CA058598
The Cancer Research Funds of Radiumhemmet
MOP-86727
The Cancer Research Funds of Radiumhemmet
GPH-129344
The Cancer Research Funds of Radiumhemmet
U19 CA148065
The Cancer Research Funds of Radiumhemmet
C1287/A16563
The Cancer Research Funds of Radiumhemmet
1111246
The Cancer Research Funds of Radiumhemmet
1173170
Stockholm County Council
18-0700
Stockholm County Council
2019-01441
Stockholm County Council
191203
Stockholm County Council
223175 (HEALTH-F2-2009-223175)
Stockholm County Council
1031333
Stockholm County Council
1109286
Stockholm County Council
CA1X01HG007491-01
Stockholm County Council
U19-CA148112
Stockholm County Council
R01-CA149429
Stockholm County Council
R01-CA058598
Stockholm County Council
MOP-86727
Stockholm County Council
GPH-129344
Stockholm County Council
U19 CA148065
Stockholm County Council
C1287/A16563
Stockholm County Council
1111246
Stockholm County Council
1173170
Märit and Hans Rausing´s initiative against Breast cancer
18-0700
Märit and Hans Rausing´s initiative against Breast cancer
2019-01441
Märit and Hans Rausing´s initiative against Breast cancer
191203
Märit and Hans Rausing´s initiative against Breast cancer
500395
Märit and Hans Rausing´s initiative against Breast cancer
223175 (HEALTH-F2-2009-223175)
Märit and Hans Rausing´s initiative against Breast cancer
1031333
Märit and Hans Rausing´s initiative against Breast cancer
1109286
Märit and Hans Rausing´s initiative against Breast cancer
CA1X01HG007491-01
Märit and Hans Rausing´s initiative against Breast cancer
U19-CA148112
Märit and Hans Rausing´s initiative against Breast cancer
R01-CA149429
Märit and Hans Rausing´s initiative against Breast cancer
R01-CA058598
Märit and Hans Rausing´s initiative against Breast cancer
MOP-86727
Märit and Hans Rausing´s initiative against Breast cancer
GPH-129344
Märit and Hans Rausing´s initiative against Breast cancer
U19 CA148065
Märit and Hans Rausing´s initiative against Breast cancer
C1287/A16563
Märit and Hans Rausing´s initiative against Breast cancer
1111246
Märit and Hans Rausing´s initiative against Breast cancer
1173170
NHMRC project
18-0700
NHMRC project
2019-01441
NHMRC project
191203
NHMRC project
500395
NHMRC project
223175 (HEALTH-F2-2009-223175)
NHMRC project
1031333
NHMRC project
1109286
NHMRC project
CA1X01HG007491-01
NHMRC project
U19-CA148112
NHMRC project
R01-CA149429
NHMRC project
R01-CA058598
NHMRC project
MOP-86727
NHMRC project
GPH-129344
NHMRC project
U19 CA148065
NHMRC project
C1287/A16563
NHMRC project
1111246
NHMRC project
1173170
Ovarian Cancer Association Consortium (OCAC)
18-0700
Ovarian Cancer Association Consortium (OCAC)
2019-01441
Ovarian Cancer Association Consortium (OCAC)
191203
Ovarian Cancer Association Consortium (OCAC)
500395
Ovarian Cancer Association Consortium (OCAC)
223175 (HEALTH-F2-2009-223175)
Ovarian Cancer Association Consortium (OCAC)
1031333
Ovarian Cancer Association Consortium (OCAC)
1109286
Ovarian Cancer Association Consortium (OCAC)
CA1X01HG007491-01
Ovarian Cancer Association Consortium (OCAC)
U19-CA148112
Ovarian Cancer Association Consortium (OCAC)
R01-CA149429
Ovarian Cancer Association Consortium (OCAC)
R01-CA058598
Ovarian Cancer Association Consortium (OCAC)
MOP-86727
Ovarian Cancer Association Consortium (OCAC)
GPH-129344
Ovarian Cancer Association Consortium (OCAC)
U19 CA148065
Ovarian Cancer Association Consortium (OCAC)
C1287/A16563
Ovarian Cancer Association Consortium (OCAC)
1111246
Ovarian Cancer Association Consortium (OCAC)
1173170
US National Institutes of Health
18-0700
US National Institutes of Health
2019-01441
US National Institutes of Health
191203
US National Institutes of Health
500395
US National Institutes of Health
223175 (HEALTH-F2-2009-223175)
US National Institutes of Health
1031333
US National Institutes of Health
1109286
US National Institutes of Health
MOP-86727
US National Institutes of Health
GPH-129344
US National Institutes of Health
U19 CA148065
US National Institutes of Health
C1287/A16563
US National Institutes of Health
1111246
US National Institutes of Health
1173170
Canadian Institutes of Health Research
18-0700
Canadian Institutes of Health Research
2019-01441
Canadian Institutes of Health Research
191203
Canadian Institutes of Health Research
500395
Canadian Institutes of Health Research
223175 (HEALTH-F2-2009-223175)
Canadian Institutes of Health Research
1031333
Canadian Institutes of Health Research
1109286
Canadian Institutes of Health Research
CA1X01HG007491-01
Canadian Institutes of Health Research
U19-CA148112
Canadian Institutes of Health Research
R01-CA149429
Canadian Institutes of Health Research
R01-CA058598
Canadian Institutes of Health Research
MOP-86727
Canadian Institutes of Health Research
GPH-129344
Canadian Institutes of Health Research
U19 CA148065
Canadian Institutes of Health Research
C1287/A16563
Canadian Institutes of Health Research
1111246
Canadian Institutes of Health Research
1173170
Ovarian Cancer Research Fund
18-0700
Ovarian Cancer Research Fund
2019-01441
Ovarian Cancer Research Fund
191203
Ovarian Cancer Research Fund
500395
Ovarian Cancer Research Fund
223175 (HEALTH-F2-2009-223175)
Ovarian Cancer Research Fund
1031333
Ovarian Cancer Research Fund
1109286
Ovarian Cancer Research Fund
CA1X01HG007491-01
Ovarian Cancer Research Fund
U19-CA148112
Ovarian Cancer Research Fund
R01-CA149429
Ovarian Cancer Research Fund
R01-CA058598
Ovarian Cancer Research Fund
MOP-86727
Ovarian Cancer Research Fund
GPH-129344
Ovarian Cancer Research Fund
U19 CA148065
Ovarian Cancer Research Fund
C1287/A16563
Ovarian Cancer Research Fund
1111246
Ovarian Cancer Research Fund
1173170
Genome Canada
18-0700
Genome Canada
2019-01441
Genome Canada
191203
Genome Canada
500395
Genome Canada
223175 (HEALTH-F2-2009-223175)
Genome Canada
1031333
Genome Canada
1109286
Genome Canada
CA1X01HG007491-01
Genome Canada
U19-CA148112
Genome Canada
R01-CA149429
Genome Canada
R01-CA058598
Genome Canada
MOP-86727
Genome Canada
GPH-129344
Genome Canada
U19 CA148065
Genome Canada
C1287/A16563
Genome Canada
1111246
Genome Canada
1173170
NIH
18-0700
NIH
2019-01441
NIH
191203
NIH
500395
NIH
223175 (HEALTH-F2-2009-223175)
NIH
1031333
NIH
1109286
NIH
CA1X01HG007491-01
NIH
U19-CA148112
NIH
R01-CA149429
NIH
R01-CA058598
NIH
MOP-86727
NIH
GPH-129344
NIH
U19 CA148065
NIH
C1287/A16563
NIH
1111246
NIH
1173170
Cancer UK
18-0700
Cancer UK
2019-01441
Cancer UK
191203
Cancer UK
500395
Cancer UK
223175 (HEALTH-F2-2009-223175)
Cancer UK
1031333
Cancer UK
1109286
Cancer UK
CA1X01HG007491-01
Cancer UK
U19-CA148112
Cancer UK
R01-CA149429
Cancer UK
R01-CA058598
Cancer UK
MOP-86727
Cancer UK
GPH-129344
Cancer UK
U19 CA148065
Cancer UK
C1287/A16563
Cancer UK
1111246
Cancer UK
1173170
National Health and Medical Research Council
18-0700
National Health and Medical Research Council
2019-01441
National Health and Medical Research Council
191203
National Health and Medical Research Council
500395
National Health and Medical Research Council
223175 (HEALTH-F2-2009-223175)
National Health and Medical Research Council
CA1X01HG007491-01
National Health and Medical Research Council
U19-CA148112
National Health and Medical Research Council
R01-CA149429
National Health and Medical Research Council
R01-CA058598
National Health and Medical Research Council
MOP-86727
National Health and Medical Research Council
GPH-129344
National Health and Medical Research Council
U19 CA148065
National Health and Medical Research Council
C1287/A16563
National Health and Medical Research Council
1111246
National Health and Medical Research Council
1173170