ORCID Profile
0000-0002-5589-3622
Current Organisations
Skånes universitetssjukhus Lund
,
Lund University
,
Skåne University Hospital
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Publisher: MDPI AG
Date: 26-01-2020
Abstract: Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2–4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.
Publisher: Springer Science and Business Media LLC
Date: 15-05-2012
DOI: 10.1038/BJC.2012.160
Publisher: Springer Science and Business Media LLC
Date: 06-10-2022
DOI: 10.1038/S42003-022-03978-6
Abstract: The contribution of germline copy number variants (CNVs) to risk of developing cancer in in iduals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
Publisher: Hindawi Limited
Date: 12-03-2018
DOI: 10.1002/HUMU.23406
Publisher: Springer Science and Business Media LLC
Date: 20-05-2011
Publisher: Hindawi Limited
Date: 09-2019
DOI: 10.1002/HUMU.23818
Publisher: Springer Science and Business Media LLC
Date: 27-04-2016
DOI: 10.1038/NCOMMS11375
Abstract: Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations ( P × 10 −8 ) with oestrogen receptor (ER)-negative breast cancer and BRCA1 -associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5 , a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations ( P .05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2009
Publisher: Public Library of Science (PLoS)
Date: 04-2015
Publisher: Springer Science and Business Media LLC
Date: 04-2012
DOI: 10.1186/BCR3169
Publisher: American Association for Cancer Research (AACR)
Date: 11-2010
DOI: 10.1158/1055-9965.EPI-10-0517
Abstract: Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population. Methods: To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85 95% CI, 0.76-0.97 Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69 95% CI, 0.53-0.89 Ptrend = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers. Conclusions: CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers. Impact: The combined application of these and other recently identified genetic risk modifiers could in the future allow better in idual risk calculation and could aid in the in idualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers. Cancer Epidemiol Biomarkers Prev 19(11) 2859–68. ©2010 AACR.
Publisher: American Medical Association (AMA)
Date: 07-04-2015
Publisher: Oxford University Press (OUP)
Date: 28-02-2020
DOI: 10.1093/JNCI/DJAA030
Abstract: The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. We analyzed data from 6178 families, 125 with pathogenic variants in RAD51C, and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C: relative risk [RR] = 7.55, 95% confidence interval [CI] = 5.60 to 10.19 P = 5 × 10-40 RAD51D: RR = 7.60, 95% CI = 5.61 to 10.30 P = 5 × 10-39) and BC (RAD51C: RR = 1.99, 95% CI = 1.39 to 2.85 P = 1.55 × 10-4 RAD51D: RR = 1.83, 95% CI = 1.24 to 2.72 P = .002). For both RAD51C and RAD51D, there was a suggestion that the TOC relative risks increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 years were 11% (95% CI = 6% to 21%) for RAD51C and 13% (95% CI = 7% to 23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 years were 21% (95% CI = 15% to 29%) for RAD51C and 20% (95% CI = 14% to 28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C and RAD51D pathogenic variant carriers varied by cancer family history and could be as high as 32–36% for TOC, for carriers with two first-degree relatives diagnosed with TOC, or 44–46% for BC, for carriers with two first-degree relatives diagnosed with BC. These estimates will facilitate the genetic counseling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 03-2020
DOI: 10.1200/JCO.19.01907
Abstract: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18 95% CI, 5.82 to 8.85 P = 6.5 × 10 −76 ), ovarian cancer (RR, 2.91 95% CI, 1.40 to 6.04 P = 4.1 × 10 −3 ), pancreatic cancer (RR, 2.37 95% CI, 1.24 to 4.50 P = 8.7 × 10 −3 ), and male breast cancer (RR, 7.34 95% CI, 1.28 to 42.18 P = 2.6 × 10 −2 ). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( P for trend = 2.0 × 10 −3 ). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4% 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
Publisher: Springer Science and Business Media LLC
Date: 11-12-2008
Publisher: Springer Science and Business Media LLC
Date: 07-09-2004
DOI: 10.1038/NG1415
Publisher: American Association for Cancer Research (AACR)
Date: 05-2011
DOI: 10.1158/1055-9965.EPI-10-0909
Abstract: Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71–1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59–1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev 20(5) 1032–8. ©2011 AACR.
Publisher: Springer Science and Business Media LLC
Date: 26-09-2012
Publisher: Oxford University Press (OUP)
Date: 02-09-2011
DOI: 10.1093/HMG/DDR388
Publisher: Springer Science and Business Media LLC
Date: 12-01-2015
DOI: 10.1038/NG.3185
Publisher: Springer Science and Business Media LLC
Date: 29-02-2016
DOI: 10.1038/NG.3521
Publisher: Springer Science and Business Media LLC
Date: 23-10-2017
DOI: 10.1038/NG.3785
Publisher: Public Library of Science (PLoS)
Date: 29-06-2012
Publisher: Springer Science and Business Media LLC
Date: 25-04-2015
Publisher: American Association for Cancer Research (AACR)
Date: 02-2020
DOI: 10.1158/0008-5472.CAN-19-1840
Abstract: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk in idual.
Publisher: Elsevier BV
Date: 05-2016
No related grants have been discovered for Hans Ehrencrona.