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- Dennis, J, et al.
(author)
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Rare germline copy number variants (CNVs) and breast cancer risk
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 65-
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Journal article (peer-reviewed)abstract
- Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E−18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
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| 4. |
- Jung, Audrey Y, et al.
(author)
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Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes : pooled analysis of population-based studies
- 2022
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In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:12, s. 1706-1719
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Journal article (peer-reviewed)abstract
- BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.METHODS: Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative) and by invasiveness. All statistical tests were 2-sided.RESULTS: Compared to nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46; for multiparous women with luminal A-like tumors 20-<25 years after last birth and 45-<50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95%CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95%CI = 0.79 to 1.34, for multiparous women 25 to < 30 years after last birth). Older age at first birth (P-heterogeneity<.001 for triple-negative compared to luminal-A like) and breastfeeding (P-heterogeneity<.001 for triple-negative compared to luminal-A like) were associated with lower risk of triple-negative but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.CONCLUSION: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.
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| 5. |
- Jimbo, Ryo, et al.
(author)
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The impact of a modified cutting flute implant design on osseointegration
- 2014
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In: International Journal of Oral and Maxillofacial Surgery. - : Elsevier. - 0901-5027 .- 1399-0020. ; 43:7, s. 883-888
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Journal article (peer-reviewed)abstract
- Information concerning the effects of the implant cutting flute design on initial stability and its influence on osseointegration in vivo is limited. This study evaluated the early effects of implants with a specific cutting flute design placed in the sheep mandible. Forty-eight dental implants with two different macrogeometries (24 with a specific cutting flute design Blossom group; 24 with a self-tapping design - DT group) were inserted into the mandibular bodies of six sheep; the maximum insertion torque was recorded. Samples were retrieved and processed for histomorphometric analysis after 3 and 6 weeks. The mean insertion torque was lower for Blossom implants (P < 0.001). No differences in histomorphometric results were observed between the groups. At 3 weeks, P = 0.58 for bone-to-implant contact (BIC) and P = 0.52 for bone area fraction occupied (BAFO); at 6 weeks, P = 0.55 for BIC and P = 0.45 for BAFO. While no histomorphometric differences were observed, ground sections showed different healing patterns between the implants, with better peri-implant bone organization around those with the specific cutting flute design (Blossom group). Implants with the modified cutting flute design had a significantly reduced insertion torque compared to the DT implants with a traditional cutting thread, and resulted in a different healing pattern.
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| 6. |
- Yung, Diana E., et al.
(author)
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Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy
- 2017
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In: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 5:7, s. 974-981
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Journal article (peer-reviewed)abstract
- Background: Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. Materials and methods: This was a retrospective, multicentre study (2010–2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. Results: Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn’s disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3–11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92–0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. Conclusion: In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.
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