| 1. |
- Ali, MA, et al.
(författare)
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Association of Microcalcification Clusters with Short-term Invasive Breast Cancer Risk and Breast Cancer Risk Factors
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 14604-
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Tidskriftsartikel (refereegranskat)abstract
- Using for-presentation and for-processing digital mammograms, the presence of microcalcifications has been shown to be associated with short-term risk of breast cancer. In a previous article we developed an algorithm for microcalcification cluster detection from for-presentation digital mammograms. Here, we focus on digitised mammograms and use a three-step algorithm. In total, 253 incident invasive breast cancer cases (with a negative mammogram between three months and two years before diagnosis, from which we measured microcalcifications) and 728 controls (also with prior mammograms) were included in a short-term risk study. After adjusting for potential confounding variables, we found evidence of an association between the number of microcalcification clusters and short-term (within 3–24 months) invasive breast cancer risk (per cluster OR = 1.30, 95% CI = (1.11, 1.53)). Using the 728 postmenopausal healthy controls, we also examined association of microcalcification clusters with reproductive factors and other established breast cancer risk factors. Age was positively associated with the presence of microcalcification clusters (p = 4 × 10−04). Of ten other risk factors that we studied, life time breastfeeding duration had the strongest evidence of association with the presence of microcalcifications (positively associated, unadjusted p = 0.001). Developing algorithms, such as ours, which can be applied on both digitised and digital mammograms (in particular for presentation images), is important because large epidemiological studies, for deriving markers of (clinical) risk prediction of breast cancer and prognosis, can be based on images from these different formats.
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| 2. |
- Cheng, THT, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 17369-
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Tidskriftsartikel (refereegranskat)abstract
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
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| 3. |
- Darabi, H, et al.
(författare)
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Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 32512-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.
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| 4. |
- Dork, T, et al.
(författare)
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Two truncating variants in FANCC and breast cancer risk
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12524-
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Tidskriftsartikel (refereegranskat)abstract
- Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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| 5. |
- Escala-Garcia, M, et al.
(författare)
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Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19787-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
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| 6. |
- Grassmann, F, et al.
(författare)
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A systems genomics approach to uncover the molecular properties of cancer genes
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 18392-
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Tidskriftsartikel (refereegranskat)abstract
- Genes involved in cancer are under constant evolutionary pressure, potentially resulting in diverse molecular properties. In this study, we explore 23 omic features from publicly available databases to define the molecular profile of different classes of cancer genes. Cancer genes were grouped according to mutational landscape (germline and somatically mutated genes), role in cancer initiation (cancer driver genes) or cancer survival (survival genes), as well as being implicated by genome-wide association studies (GWAS genes). For each gene, we also computed feature scores based on all omic features, effectively summarizing how closely a gene resembles cancer genes of the respective class. In general, cancer genes are longer, have a lower GC content, have more isoforms with shorter exons, are expressed in more tissues and have more transcription factor binding sites than non-cancer genes. We found that germline genes more closely resemble single tissue GWAS genes while somatic genes are more similar to pleiotropic cancer GWAS genes. As a proof-of-principle, we utilized aggregated feature scores to prioritize genes in breast cancer GWAS loci and found that top ranking genes were enriched in cancer related pathways. In conclusion, we have identified multiple omic features associated with different classes of cancer genes, which can assist prioritization of genes in cancer gene discovery.
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| 7. |
- Li, JM, et al.
(författare)
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Associations between childhood body size and seventeen adverse outcomes: analysis of 65,057 European women
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 16917-
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Tidskriftsartikel (refereegranskat)abstract
- Large childhood body size has been consistently shown to be associated with decreased breast cancer risk. However, it is important to consider the effects of a large childhood body size on other adult diseases. It is not clear if the associations between childhood body size and adult diseases will persist if they later attain healthy weight. The associations between body size at age 7 and 17 adverse outcomes in adulthood were examined using Cox models in a Swedish study of 65,057 women. Large body size at age 7, when compared to small body size, was associated with decreased risk for breast cancer (HR [95% CI]: 0.81 [0.70–0.93]) and increased risks for anorexia (2.13 [1.63–2.77]) and bulimia (1.91 [1.35–2.70]). Neither adjusting for adult BMI nor restricting the dataset to lean adults (BMI < 25 kg/m2) attenuated the associations. While large body size at age 7 by itself was positively associated with increased risks of diabetes (1.34 [1.16–1.55]), PCOS (1.69 [1.13–2.51]) and hypertension (before age 60), the associations were no longer significant after controlling for adult BMI. No clear associations were found with the remaining adverse outcomes (cervical, uterine, melanoma, colon cancer, depression, ovarian cyst, stroke, hyperlipidemia, heart failure, myocardial infarction, and angina pectoris).
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| 8. |
- Liu, JJ, et al.
(författare)
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Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 9688-
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Tidskriftsartikel (refereegranskat)abstract
- In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859–1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482–1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
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| 9. |
- Liu, JJ, et al.
(författare)
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rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 36874-
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Tidskriftsartikel (refereegranskat)abstract
- NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3′-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936–1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969–1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905–1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.
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| 10. |
- Setiawan, A, et al.
(författare)
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Patterns of acute inflammatory symptoms prior to cancer diagnosis
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 67-
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Tidskriftsartikel (refereegranskat)abstract
- Although many studies have examined the role of chronic inflammation in cancer development, few studies discuss the patterns of acute inflammation prior to cancer diagnosis. Patients with lung, colorectal, prostate, or breast cancer between 1 July 2006 and 31 December 2009 and their metastatic status at diagnosis were determined through the Swedish Cancer Register. Non-steroidal anti-inflammatory drugs (NSAIDs) use in the year prior to cancer diagnosis was assessed through the Swedish Prescribed Drug Register. There were 13,945 patients identified with breast cancer, 6501 with prostate cancer, 5508 with lung cancer, and 12,723 with colon cancer. For metastatic patients, there is strong evidence of higher NSAIDs use 1–3 months compared to 10–12 months prior to diagnosis (breast odds ratio (OR) = 3.54, 95% CI 2.26–5.54; prostate OR = 3.90, 95% CI 3.10–4.90; lung OR = 2.90 95% CI 2.44–3.44; colorectal OR = 1.67, 95% CI 1.36–2.05). For non-metastatic patients, increased NSAIDs use 1–3 months prior to diagnosis was also observed, but only to a smaller extent for lung and prostate cancer (prostate OR = 1.48, 95% CI 1.27–1.72; lung 1.41, 95% CI 1.19–1.67). In conclusion, if NSAIDs use reflects underlying inflammatory symptoms, there is support for the hypothesis that advanced cancer was associated with an acute inflammatory process.
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