| 11. |
- Ellberg, Carolina, et al.
(författare)
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Impact of a paternal origin of germline BRCA1/2 mutations on the age at breast and ovarian cancer diagnosis in a Southern Swedish cohort.
- 2015
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 54:1, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis. This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to families registered between 1993 and 2011 at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden. Cox proportional hazard ratios were used to analyze time to breast or ovarian cancer diagnosis. A novel finding was that carriers of BRCA1 mutations of paternal origin were 4 years older at age of ovarian cancer (P = 0.009) compared with those carrying a BRCA1 mutation of maternal origin. BRCA1 carriers with mutations of paternal origin were 4 years younger at breast cancer diagnosis (P = 0.017) compared with those carrying a BRCA1 mutation of maternal origin, which is in agreement with three previous studies. Both findings were adjusted for of year of inclusion, birth date, and oral contraceptive pill use. No associations between parental origin of BRCA2 mutations and time to breast or ovarian cancer diagnosis were found. An attempt to handle a potential selection bias regarding use of oral contraceptives was made using multiple imputations by chained equations. The observed age difference may allow a greater understanding of mechanisms associated with the differences in cancer penetrance in BRCA1/2 mutation carriers, some of which may depend on paternal origin. © 2014 Wiley Periodicals, Inc.
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| 12. |
- Ellberg, Carolina
(författare)
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Insights into breast cancer: New familial patterns and identification of a potential predictive marker
- 2014. - 2014:49
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The last proportion of heredity in breast cancer has proven to be somewhat elusive despite massive attempts to identify the associated factors. Approximately 50 percent of breast cancer caused by familial factors is currently explained. The five-year survival for breast cancer patients is excellent; however, breast cancer is considered a chronic disease, and given enough time, new tumors can develop. Women age 40 and older are offered screening mammography. However, population screening is expensive, and being able to pinpoint those who are at high risk of breast cancer would be beneficial. Both genetic and environmental risk factors could be used to select women who need screening. A major aim of this thesis was to try to identify potential familial patterns as candidates for hereditary breast cancer. In Paper I, we studied horizontal family history of breast cancer in relation to histology to discover a candidate phenotype for recessive inheritance. A horizontal pedigree pattern is characterized by two or more sisters diagnosed with breast cancer, without a family history of breast cancer in prior generations. A horizontal inheritance was more common in patients with tubular carcinoma compared with other histologic subtypes. Therefore, we propose that breast cancer patients with tubular carcinoma who have a sister or sisters diagnosed with breast cancer are candidates for genetic studies when searching for a recessively inherited predisposing gene. In paper II, we studied the occurrence of cancer in first-degree relatives of breast cancer patients diagnosed with the lobular carcinoma histologic subtype compared with other histological subtypes of breast cancer. We found a hereditary pattern involving breast cancer patients with lobular carcinoma and having a father diagnosed with cancer. The association was independent of a family history of breast cancer in sisters, the mother and grandmothers. Similarly, even though prostate cancer was prominent in the fathers, the association remained after removal of fathers diagnosed with prostate cancer. In paper III, we confirmed a previously reported younger age at breast cancer diagnosis in carriers of a BRCA1 mutation of paternal origin compared with maternal origin. Additionally, we observed an older age at ovarian cancer diagnosis in carriers of a BRCA1 mutation of paternal origin compared with maternal origin. No such observations were observed for BRCA2 mutation carriers. In paper IV, we studied the occurrence of spider telangiectasias at the time of breast cancer diagnosis in relation to hormonal risk factors. We reported that the occurrence of spider telangiectasias was associated with several hormonal risk factors such as weight, parity, history of oral contraceptive use, and menopausal hormone therapy use. A better overall survival was observed in older breast cancer patients who displayed spider telangiectasias at the time of breast cancer diagnosis.
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| 13. |
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| 14. |
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| 15. |
- Escala-Garcia, Maria, et al.
(författare)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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| 16. |
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| 17. |
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| 18. |
- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 19. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 20. |
- Gerell, Manne, et al.
(författare)
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Kamerabevakning i polisens brottsutredande arbete
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- För att få en bättre förståelse för hur kamerabevakningen fungerar, framför allt med fokus på det brottsutredande arbetet, har ett utvecklingsprojekt fokuserat på detta. Inom ramen för projektet har flera olika sektioner av polisen varit involverade för att från hösten 2020 till våren 2021 flagga brott som begåtts på utpekade kamerabevakade platser och säkerställa att dessa följs upp i utredningsarbetet. Inflödet av brott som gått att följa var betydligt mindre än väntat, och ett inledningsvis snävt definierat upptagningsområde utökades allt eftersom. Trots det inkom bara 40 mängdbrott på kamerabevakade platser inom ramen för projektet. Av dessa kunde brottet identifieras på kamerabilderna i 15 fall. I fem av de 15 fallen kunde gärningspersonen ses relativt tydligt, och två av dessa gärningspersoner identifierades också. Inom ramen för intervjuer med de som på olika sätt arbetar med brottsutredningar och kameramaterial framkom också att det för den typ av relativt milda mängdbrott som här studerats är avgörande att få bra möjlighet till identifiering av gärningsperson för att kunna nå framgång i arbetet. Det innebär att ett sätt att effektivisera arbetet med kamerorna är att justera placering och/eller inzoomning för att oftare få möjlighet att identifiera gärningspersoner. För grövre brott, t ex skjutningar eller våldtäkter, kan dock även mindre detaljerade kamerabilder föra en utredning framåt, vilket innefattar betydligt fler brott.
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