GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 52, No. 6 ( 2020-06), p. 572-581
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1494946-5
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-08-29)
    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.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2615211-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-04-13)
    Abstract: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values  〈  5 × 10 –8 as genome-wide significant, and p-values  〈  1 × 10 –5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values  〈  1 × 10 5 . The strongest evidence was found for rs4674019 (p-value = 2.27 × 10 –7 ), which showed genome-wide significant interaction (p-value = 3.8 × 10 –8 ) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen–progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Cancer Research Communications, American Association for Cancer Research (AACR), Vol. 2, No. 4 ( 2022-04-08), p. 211-219
    Abstract: Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P & lt; 0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test. After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE = 4.44 × 10−6). In this transcriptome-informed genome-wide gene–environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk. Our study suggests a limited role of gene–environment interactions in breast cancer risk.
    Type of Medium: Online Resource
    ISSN: 2767-9764
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 3098144-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5883-5883
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 5883-5883
    Abstract: Background: Identification of women at elevated risk for highly proliferative, poor prognosis breast cancers could have important implications for screening and prevention. Genome-wide association studies (GWAS) have found & gt;200 single nucleotide polymorphisms (SNPs) associated with breast cancer risk, with many SNPs differentially associated with ER status or intrinsic subtype. We hypothesized that some of these SNPs are preferentially associated with more proliferative tumors, while others are preferentially associated with less proliferative tumors. In this study, we aimed to build a polygenic risk score (PRS) predictive of proliferative tumors, using the GWAS-identified SNPs. Methods: We used data from 3 studies that included array-based SNP genotyping and tumor transcriptomic data: The Cancer Genome Atlas, METABRIC, and the I-SPY 2 Trial (total n=2,467). Our outcome was the risk of recurrence score weighted on proliferation (ROR-P), a validated tumor prognostic signature. Using the breast cancer risk SNPs, we built respective linear regression models to predict ROR-P, with genetic ancestry, study, and ER status as covariates. We performed 5-fold cross-validation and used the model r2 to identify the optimal p-value threshold for including SNPs in the PRS. To decrease uncertainty of our estimates, we performed 100 repeats across the pooled datasets. To test whether this model predicted poor prognosis breast cancers, we first used it to impute ROR-P among genotyped breast cancer cases in UK Biobank (UKB). We then examined the association between “genetically predicted” ROR-P and breast cancer-specific survival using Cox proportional hazards models adjusted for genetic ancestry and age at diagnosis. Results: Associations between 224 breast cancer SNPs and ROR-P were tested. The best-performing model in cross-validation contained 96 SNPs, each associated with ROR-P at p & lt; 0.45, with model r2 0.054. The SNPs with the strongest positive correlations with ROR-P included those discovered in GWAS for HER2-positive and ER-negative cancers, both of which tend to be highly proliferative. Among 7,247 incident cancers in UKB, higher genetically predicted ROR-P was associated with shorter survival, with a per-standard deviation hazard ratio of 1.14 (95% CI 1.05-1.24, p = 0.002). Conclusions: We used breast cancer susceptibility SNPs to construct a PRS fitted to ROR-P, a prognostic signature recapitulating tumor proliferation. This PRS was associated with worse clinical outcomes in breast cancer cases from UKB. Our results suggest that correlations between SNPs and tumor gene expression can be used to “tune” PRS to tumor phenotype, e.g. proliferation. Highly proliferative tumors are more likely to present as advanced cancers even among women getting routine screening. If replicated in other datasets, our findings could be used to identify women who may especially benefit from tailored screening and prevention. Citation Format: Yiwey Shieh, Jacquelyn Roger, Scott Huntsman, Donglei Hu, Jovia L. Nierenberg, Pooja Middha Kapoor, Christina Yau, Gillian Hirst, Laura van 't Veer, Laura Esserman. Development and testing of a polygenic risk score for proliferative breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5883.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    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 ...
  • 6
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-05-14)
    Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2553671-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 30, No. 4 ( 2021-04-01), p. 623-642
    Abstract: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj & gt; 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)] , high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus & lt;20 years at first pregnancy [0.79 (0.72–0.86)]; & gt;0– & lt;5 years versus ≥10 years since last full-term birth [1.31 (1.11–1.55)]; ever versus never use of oral contraceptives [0.91 (0.87–0.96)] ; ever versus never use of menopausal hormone therapy, including current estrogen–progestin therapy [0.61 (0.54–0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02–1.21) for current versus never smoking. Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 3670-3670
    Abstract: Background: Studies have reported differences in associations between breast cancer risk factors and subtypes defined by hormone receptor status, particularly estrogen receptor (ER) positive versus ER negative tumors. Most studies have been conducted in women of European descent, and an expanding body of literature in other populations suggests differences by race/ethnicity. Clarifying whether associations between risk factors and disease subtypes are consistent across racial/ethnic populations has important implications for understanding disease etiology and for improving risk prediction models. To address this question, we conducted a qualitative literature review to investigate the consistency in associations between multiple breast cancer risk factors and risk of tumor subtypes in women of African, Asian, Hispanic, and European descent. Methods: We searched PubMed for publications between January 1, 1990 and June 8, 2021 that reported associations between breast cancer risk factors and risk of subtypes of the disease. We evaluated 19 risk factors, including reproductive, anthropometric, lifestyle, and diet factors, as well as medical history and use of menopausal hormone therapy (MHT). Subtypes were defined as ER positive or negative (specifically triple negative when available). We prioritized review studies (i.e., meta-analyses, systematic reviews, and pooled analyses) and included individual studies with populations not included in the reviews. The number of publications per risk factor ranged from 3 for calcium intake to 28 for parity, with up to 7 reviews per risk factor. Most publications reported estimates for women of European descent, followed by Asian, African, and Hispanic. Evidence of subtype heterogeneity was determined by expert review. Results: There was strong evidence of association between reproductive factors and MHT with risk of ER positive but not ER negative disease. Parity, younger age at first birth and older age at menarche were associated with lower risk of ER positive disease, while MHT use was associated with higher risk of ER positive disease. For these risk factors, we did not find evidence that risk associations or etiologic heterogeneity varied by race/ethnicity. For the other risk factors, there was limited or no evidence of heterogeneity in risk associations by subtype, which was consistent across racial/ethnic groups. Few publications, however, specifically studied women of non-European ancestry. Conclusion: For most breast cancer risk factors, evidence is insufficient to evaluate differences in ER-specific risk associations by race/ethnicity. More studies are needed to evaluate subtype-specific breast cancer risk factors in diverse populations, which will be important for informing the development of multi-ethnic/racial BC risk prediction models that account for subtype heterogeneity. Citation Format: Amber N. Hurson, Thomas U. Ahearn, Renske Keeman, Mustapha Abubakar, Audrey Y. Jung, Pooja Middha Kapoor, Hela Koka, Xiaohong R. Yang, Jenny Chang-Claude, Elena Martínez, Rulla M. Tamimi, Melissa A. Troester, Elisa V. Bandera, Marjanka K. Schmidt, Montserrat Garcia-Closas. Systematic literature review of risk factor associations with breast cancer subtypes in women of African, Asian, Hispanic, and European descents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3670.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    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 ...
  • 9
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 3631-3631
    Abstract: Background: Genetic susceptibility to breast cancer has been studied extensively in European ancestry populations, but few studies have addressed genetic susceptibility in non-European women. Latinas are a genetically diverse group with contributions from European, African, and Indigenous American ancestries. Genome-wide association studies (GWAS) have identified unique variants in this population, particularly at the 6q25 locus. We conducted a transcriptome-wide association study (TWAS) to identify novel genes associated with risk of breast cancer in Latinas. Methods: We used individual level GWAS data from 2,396 Latina cases and 6,505 Latina controls from the studies in Northern California (San Francisco Bay Area Breast Cancer Study, Northern California Breast Cancer Family Registry and Kaiser Permanente Genetic Epidemiology Research on Aging Cohort), Southern California (Multi-ethnic Cohort) and Mexico (CAMA study). We analyzed the association between genetically predicted whole blood (WB) gene expression and breast cancer risk using newly developed TWAS models based on 784 Mexican American individuals. We also conducted parallel analyses using breast mammary tissue (BT) TWAS models from GTEx v8. All analyses were adjusted for age, ancestry, and study. Associations with false discovery rate (FDR) probability & lt;0.05 were considered statistically significant. Results: At FDR & lt;0.05, we identified 20 genes from BT and 39 genes from WB. Seven of the genes were significantly associated in both the WB models and GTEx BT models. Increased expression of MIB2 (pFDR = 4.74x10-17 (WB) and 1.22x10-4 (BT)), NBPF26 (pFDR = 1.30x10-7 (WB) and 7.43x10-8 (BT)), SLC35E2B (pFDR = 1.12x10-4 (WB) and 5.47x10-5 (BT)), and FAM30A (pFDR = 1.18x10-10 (WB) and 9.27x10-3 (BT)) was associated with increased risk of breast cancer risk, whereas increased expression of SLC35E2A (pFDR = 8.17x10-6 (WB) and 1.55x10-3 (BT)) and HCP5B (pFDR = 1.84x10-3 (WB) and 2.19x10-3 (BT)) was associated with decreased breast cancer risk. Increased expression of PDGFA was associated with increased risk (pFDR = 1.30x10-7) in GTEx BT reference models but decreased risk (pFDR = 2.34x10-10) in the ancestry-specific WB model. Conclusion: Our study is the first TWAS investigating the relationship between genetically predicted gene expression and breast cancer risk in Latinas. By leveraging gene expression prediction models that capture eQTLs that are more common in populations with Indigenous American ancestry, we have identified some novel genes associated with breast cancer risk in Latinas. Of these, MIB2 is a strong candidate for a mechanistic role in breast carcinogenesis in Latinas. MIB2 is involved in Notch signaling which plays an important role in breast carcinogenesis via its mismatched receptor-ligand interaction. Our study highlights the role of ancestry-based prediction models in TWAS analyses. Citation Format: Pooja Middha Kapoor, Angel C. Mak, Linda Kachuri, Donglei Hu, Scott Huntsman, Lawrence H. Kushi, Christopher Haiman, Esther M. John, Gabriela Torres-Mejia, Esteban G. Burchard, Susan L. Neuhausen, Laura Fejerman, Elad Ziv. Transcriptome-wide association study identifies novel genes associated with breast cancer susceptibility in Latinas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3631.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    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 ...
  • 10
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 113, No. 3 ( 2021-03-01), p. 329-337
    Abstract: We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...