Novel Shared Heritable Candidate Risk Loci of Breast and Endometrial Cancer—A Swedish Haplotype Genome-Wide Association Study
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.
Institutions
Authors
Funding
CIHR Grant MOP-86727National Health and Medical Research Council Grant 1109286National Health and Medical Research Council Grant ID1111246US National Institutes of Health Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)Märit and Hans Rausing´s Initiative Against Breast Cancer FundingStockholms Läns Landsting Grant 500395Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskDiscovery, Biology and Risk of Inherited Variants in Breast CancerCancerfonden Grant 18-0700National Health and Medical Research Council Grant ID1173170Discovery, Biology and Risk of Inherited Variants in Breast CancerOvarian Cancer Research Fund Grant 268201200008ICollaborative Genetic Study of Ovarian Cancer RiskVetenskapsrådet Grant 2019-01441The Mitochondrial Genome and Ovarian Cancer RiskNational Health and Medical Research Council Grant 1031333Cancer UK Grant Grant C1287The Cancer Research Funds of Radiumhemmet Grant 191203Cancer UK Grant Grant A16563European Community's Seventh Framework Programme Grant 223175Genome Canada Grant Grant GPH-129344Collaborative Genetic Study of Ovarian Cancer RiskSwedish Cancer Society Grant 2019-01441Swedish Cancer Society Grant 191203Swedish Cancer Society Grant 500395Swedish Cancer Society Grant 223175 (HEALTH-F2-2009-223175)Swedish Cancer Society Grant 1031333Swedish Cancer Society Grant 1109286Swedish Cancer Society Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskSwedish Cancer Society Grant MOP-86727Swedish Cancer Society Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerSwedish Cancer Society Grant C1287/A16563Swedish Cancer Society Grant 1111246Swedish Cancer Society Grant 1173170Swedish Research Council Grant 18-0700Swedish Research Council Grant 191203Swedish Research Council Grant 500395Swedish Research Council Grant 223175 (HEALTH-F2-2009-223175)Swedish Research Council Grant 1031333Swedish Research Council Grant 1109286Swedish Research Council Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskSwedish Research Council Grant MOP-86727Swedish Research Council Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerSwedish Research Council Grant C1287/A16563Swedish Research Council Grant 1111246Swedish Research Council Grant 1173170The Cancer Research Funds of Radiumhemmet Grant 18-0700The Cancer Research Funds of Radiumhemmet Grant 2019-01441The Cancer Research Funds of Radiumhemmet Grant 500395The Cancer Research Funds of Radiumhemmet Grant 223175 (HEALTH-F2-2009-223175)The Cancer Research Funds of Radiumhemmet Grant 1031333The Cancer Research Funds of Radiumhemmet Grant 1109286The Cancer Research Funds of Radiumhemmet Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskThe Cancer Research Funds of Radiumhemmet Grant MOP-86727The Cancer Research Funds of Radiumhemmet Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerThe Cancer Research Funds of Radiumhemmet Grant C1287/A16563The Cancer Research Funds of Radiumhemmet Grant 1111246The Cancer Research Funds of Radiumhemmet Grant 1173170Stockholm County Council Grant 18-0700Stockholm County Council Grant 2019-01441Stockholm County Council Grant 191203Stockholm County Council Grant 223175 (HEALTH-F2-2009-223175)Stockholm County Council Grant 1031333Stockholm County Council Grant 1109286Stockholm County Council Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskStockholm County Council Grant MOP-86727Stockholm County Council Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerStockholm County Council Grant C1287/A16563Stockholm County Council Grant 1111246Stockholm County Council Grant 1173170Märit and Hans Rausing´s initiative against Breast cancer Grant 18-0700Märit and Hans Rausing´s initiative against Breast cancer Grant 2019-01441Märit and Hans Rausing´s initiative against Breast cancer Grant 191203Märit and Hans Rausing´s initiative against Breast cancer Grant 500395Märit and Hans Rausing´s initiative against Breast cancer Grant 223175 (HEALTH-F2-2009-223175)Märit and Hans Rausing´s initiative against Breast cancer Grant 1031333Märit and Hans Rausing´s initiative against Breast cancer Grant 1109286Märit and Hans Rausing´s initiative against Breast cancer Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskMärit and Hans Rausing´s initiative against Breast cancer Grant MOP-86727Märit and Hans Rausing´s initiative against Breast cancer Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerMärit and Hans Rausing´s initiative against Breast cancer Grant C1287/A16563Märit and Hans Rausing´s initiative against Breast cancer Grant 1111246Märit and Hans Rausing´s initiative against Breast cancer Grant 1173170NHMRC project Grant 18-0700NHMRC project Grant 2019-01441NHMRC project Grant 191203NHMRC project Grant 500395NHMRC project Grant 223175 (HEALTH-F2-2009-223175)NHMRC project Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskNHMRC project Grant MOP-86727NHMRC project Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerNHMRC project Grant C1287/A16563National Health and Medical Research Council Grant 1111246National Health and Medical Research Council Grant 1173170Ovarian Cancer Association Consortium (OCAC) Grant 18-0700Ovarian Cancer Association Consortium (OCAC) Grant 2019-01441Ovarian Cancer Association Consortium (OCAC) Grant 191203Ovarian Cancer Association Consortium (OCAC) Grant 500395Ovarian Cancer Association Consortium (OCAC) Grant 223175 (HEALTH-F2-2009-223175)Ovarian Cancer Association Consortium (OCAC) Grant 1031333Ovarian Cancer Association Consortium (OCAC) Grant 1109286Ovarian Cancer Association Consortium (OCAC) Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskOvarian Cancer Association Consortium (OCAC) Grant MOP-86727Ovarian Cancer Association Consortium (OCAC) Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerOvarian Cancer Association Consortium (OCAC) Grant C1287/A16563Ovarian Cancer Association Consortium (OCAC) Grant 1111246Ovarian Cancer Association Consortium (OCAC) Grant 1173170Adhesome signaling in lung injury and repairSTRONG HEART STUDY (SHS)- FIELD CENTER (FC)- TASK ORDER 001US National Institutes of Health Grant 191203US National Institutes of Health Grant 500395US National Institutes of Health Grant 223175 (HEALTH-F2-2009-223175)US National Institutes of Health Grant 1031333US National Institutes of Health Grant 1109286US National Institutes of Health Grant MOP-86727US National Institutes of Health Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerUS National Institutes of Health Grant C1287/A16563US National Institutes of Health Grant 1111246US National Institutes of Health Grant 1173170Canadian Institutes of Health Research Grant 18-0700Canadian Institutes of Health Research Grant 2019-01441Canadian Institutes of Health Research Grant 191203Canadian Institutes of Health Research Grant 500395Canadian Institutes of Health Research Grant 223175 (HEALTH-F2-2009-223175)Canadian Institutes of Health Research Grant 1031333Canadian Institutes of Health Research Grant 1109286Canadian Institutes of Health Research Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskCanadian Institutes of Health Research Grant MOP-86727Canadian Institutes of Health Research Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerCanadian Institutes of Health Research Grant C1287/A16563Canadian Institutes of Health Research Grant 1111246Canadian Institutes of Health Research Grant 1173170Ovarian Cancer Research Fund Grant 18-0700Ovarian Cancer Research Fund Grant 2019-01441Ovarian Cancer Research Fund Grant 191203Ovarian Cancer Research Fund Grant 500395Ovarian Cancer Research Fund Grant 223175 (HEALTH-F2-2009-223175)Ovarian Cancer Research Fund Grant 1031333Ovarian Cancer Research Fund Grant 1109286Ovarian Cancer Research Fund Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskOvarian Cancer Research Fund Grant MOP-86727Ovarian Cancer Research Fund Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerOvarian Cancer Research Fund Grant C1287/A16563Ovarian Cancer Research Fund Grant 1111246Ovarian Cancer Research Fund Grant 1173170Genome Canada Grant 18-0700Genome Canada Grant 2019-01441Genome Canada Grant 191203Genome Canada Grant 500395Genome Canada Grant 223175 (HEALTH-F2-2009-223175)Genome Canada Grant 1031333Genome Canada Grant 1109286Genome Canada Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskGenome Canada Grant MOP-86727Genome Canada Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerGenome Canada Grant C1287/A16563Genome Canada Grant 1111246Genome Canada Grant 1173170Adhesome signaling in lung injury and repairSTRONG HEART STUDY (SHS)- FIELD CENTER (FC)- TASK ORDER 001NIH Grant 191203NIH Grant 500395NIH Grant 223175 (HEALTH-F2-2009-223175)NIH Grant 1031333NIH Grant 1109286NIH Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskNIH Grant MOP-86727NIH Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerNIH Grant C1287/A16563NIH Grant 1111246NIH Grant 1173170Cancer UK Grant 18-0700Cancer UK Grant 2019-01441Cancer UK Grant 191203Cancer UK Grant 500395Cancer UK Grant 223175 (HEALTH-F2-2009-223175)Cancer UK Grant 1031333Cancer UK Grant 1109286Cancer UK Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskCancer UK Grant MOP-86727Cancer UK Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerCancer UK Grant C1287/A16563Cancer UK Grant 1111246Cancer UK Grant 1173170National Health and Medical Research Council Grant 18-0700National Health and Medical Research Council Grant 2019-01441National Health and Medical Research Council Grant 191203National Health and Medical Research Council Grant 500395National Health and Medical Research Council Grant 223175 (HEALTH-F2-2009-223175)National Health and Medical Research Council Grant CA1X01HG007491-01Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)The Mitochondrial Genome and Ovarian Cancer RiskCollaborative Genetic Study of Ovarian Cancer RiskNational Health and Medical Research Council Grant MOP-86727National Health and Medical Research Council Grant GPH-129344Discovery, Biology and Risk of Inherited Variants in Breast CancerNational Health and Medical Research Council Grant C1287/A16563