GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (6)
  • Radice, Paolo  (6)
  • 1
    Online Resource
    Online Resource
    Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 3 ( 2020-02-01), p. 624-638
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 3 ( 2020-02-01), p. 624-638
    Abstract: Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3′ region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63–5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71–4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12–11.54; P = 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-19-1840
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    ENIGMA CHEK2 gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk
    American Association for Cancer Research (AACR) ; 2023
    In:  Clinical Cancer Research Vol. 29, No. 16 ( 2023-08-15), p. 3037-3050
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 29, No. 16 ( 2023-08-15), p. 3037-3050
    Abstract: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT). Experimental Design: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1–CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case–control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls. Results: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)–like (N = 226). We then examined their association with breast cancer risk in the case–control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35–3.41), 1.57 (95% CI, 1.41–1.75), and 1.19 (95% CI, 1.08–1.31), respectively. The meta-analysis of population-specific datasets showed similar results. Conclusions: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-23-0212
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    19p13.1 Is a Triple-Negative–Specific Breast Cancer Susceptibility Locus
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 7 ( 2012-04-01), p. 1795-1803
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 7 ( 2012-04-01), p. 1795-1803
    Abstract: The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13] . Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-11-3364
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 20, No. 10 ( 2011-10-01), p. 2222-2231
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 20, No. 10 ( 2011-10-01), p. 2222-2231
    Abstract: Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-11-0569
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 11 ( 2017-06-01), p. 2789-2799
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 11 ( 2017-06-01), p. 2789-2799
    Abstract: Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case–control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A & gt;C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G & gt;A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G & gt;A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G & gt;T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789–99. ©2017 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-16-2568
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 21, No. 10 ( 2012-10-01), p. 1783-1791
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 21, No. 10 ( 2012-10-01), p. 1783-1791
    Abstract: Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686–breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case–control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10−29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10−143] , but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor–positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86–0.91; P = 3.13 × 10−22) but less strongly, if at all, with ER-negative (ER−) disease (OR, 0.98; 95% CI, 0.94–1.02; P = 0.26; Phet = 1.16 × 10−6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783–. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-12-0526
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...