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  • Kraft, Peter  (32)
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  • 1
    Language: English
    In: International Journal of Cancer, Dec 15, 2015, Vol.137(12), p.2837(9)
    Keywords: Breast Cancer -- Risk Factors ; Breast Cancer -- Health Aspects ; Chromosomes -- Health Aspects ; Single Nucleotide Polymorphisms -- Health Aspects ; Prostate Cancer -- Risk Factors ; Prostate Cancer -- Health Aspects
    ISSN: 0020-7136
    Source: Cengage Learning, Inc.
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  • 2
    In: American Journal of Epidemiology, 2017, Vol. 185(6), pp.452-464
    Description: Genome-wide association studies (GWAS) have identified over 100 single nucleotide polymorphisms (SNPs) associated with prostate cancer. However, information on the mechanistic basis for some associations is limited. Recent research has been directed towards the potential association of vitamin D concentrations and prostate cancer, but little is known about whether the aforementioned genetic associations are modified by vitamin D. We investigated the associations of 46 GWAS-identified SNPs, circulating concentrations of 25-hydroxyvitamin D (25(OH)D), and prostate cancer (3,811 cases, 511 of whom died from the disease, compared with 2,980 controls—from 5 cohort studies that recruited participants over several periods beginning in the 1980s). We used logistic regression models with data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) to evaluate interactions on the multiplicative and additive scales. After allowing for multiple testing, none of the SNPs examined was significantly associated with 25(OH)D concentration, and the SNP–prostate cancer associations did not differ by these concentrations. A statistically significant interaction was observed for each of 2 SNPs in the 8q24 region (rs620861 and rs16902094), 25(OH)D concentration, and fatal prostate cancer on both multiplicative and additive scales ( P  ≤ 0.001). We did not find strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of 25(OH)D. The intriguing interactions between rs620861 and rs16902094, 25(OH)D concentration, and fatal prostate cancer warrant replication.
    Keywords: 25 - Hydroxyvitamin D ; Bpc3 ; Gene - Environment Interactions ; Genome - Wide Association Studies ; Prostate Cancer
    ISSN: 0002-9262
    E-ISSN: 1476-6256
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  • 3
    In: International Journal of Cancer, 15 December 2015, Vol.137(12), pp.2837-2845
    Description: The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over‐all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta‐analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed analyses of SNPs with significant associations. In BPC3, the C allele of ‐rs3817198 was significantly associated with improved OS (HR=0.70; 95% CI: 0.58–0.85;  = 2.84 × 10; HR = 0.71; 95% CI: 0.55–0.92; HR = 0.48; 95% CI: 0.31–0.76;  = 1.45 × 10). , the C allele of ‐rs3817198 was predicted to increase expression of the tumor suppressor cyclin‐dependent kinase inhibitor 1C (). In the meta‐analysis, ‐rs3803662 was significantly associated with increased death hazard (HR =1.09; 95% CI: 1.04–1.15;  = 6.6 × 10; HR = 0.96 95% CI: 0.90–1.03; HR = 1.21; 95% CI: 1.09–1.35; =1.25 × 10). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of ‐rs3817198 and ‐rs3803662. What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast‐cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.
    Keywords: Breast Cancer ; Snp ; Survival ; Bpc3 ; Meta‐Analysis
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 4
    Language: English
    In: The American Journal of Human Genetics, 01 October 2015, Vol.97(4), pp.576-592
    Description: Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase.
    Keywords: Biology
    ISSN: 0002-9297
    E-ISSN: 1537-6605
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  • 5
    Language: English
    In: Nature genetics, 06 May 2012, Vol.44(6), pp.651-8
    Description: In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of 〉2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
    Keywords: Mosaicism ; Aging -- Genetics
    ISSN: 10614036
    E-ISSN: 1546-1718
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  • 6
    Language: English
    In: Breast Cancer Research, 2015, Vol. 17
    Description: Introduction: Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS.Methods: To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile.Results: We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons 〈0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11-1.38, P = 1.27 x 10(-4)) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99-1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09-1.42, P = 1.07 x 10(-3)). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies.Conclusions: Our study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus.
    Keywords: Medical And Health Sciences ; Clinical Medicine ; Cancer And Oncology ; Medicin Och Hälsovetenskap ; Klinisk Medicin ; Cancer Och Onkologi ; Medical And Health Sciences ; Basic Medicine ; Medical Genetics ; Medicin Och Hälsovetenskap ; Medicinska Och Farmaceutiska Grundvetenskaper ; Medicinsk Genetik
    ISSN: 1465-5411
    E-ISSN: 1465542X
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  • 7
    Language: English
    In: The Prostate, 2015, Vol. 75(15), pp. 1677-81
    Description: BACKGROUND: ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer.METHODS: We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score ≥8 or locally advanced/metastatic disease (stage T3/T4/N1/M1).RESULTS: We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95%CI = 0.87-1.08; Type B: OR = 0.92, 95%CI =n0.77-1.09; Type AB: OR = 1.25, 95%CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk.CONCLUSIONS: ABO blood type was not associated with risk of aggressive prostate cancer.
    Keywords: Abo ; Blood Type ; Genetic Epidemiology ; Prostate Cancer ; Medical And Health Sciences ; Clinical Medicine ; Urology And Nephrology ; Medicin Och Hälsovetenskap ; Klinisk Medicin ; Urologi Och Njurmedicin ; Medical And Health Sciences ; Clinical Medicine ; Cancer And Oncology ; Medicin Och Hälsovetenskap ; Klinisk Medicin ; Cancer Och Onkologi
    ISSN: 0270-4137
    E-ISSN: 10970045
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  • 8
    Language: English
    In: Nature Communications, 2018, Vol. 9(1)
    Description: Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
    Keywords: Medical And Health Sciences ; Clinical Medicine ; Cancer And Oncology ; Medicin Och Hälsovetenskap ; Klinisk Medicin ; Cancer Och Onkologi
    ISSN: 2041-1723
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  • 9
    Language: English
    In: Scelo, G., M. P. Purdue, K. M. Brown, M. Johansson, Z. Wang, J. E. Eckel-Passow, Y. Ye, et al. 2017. “Genome-wide association study identifies multiple risk loci for renal cell carcinoma.” Nature Communications 8 (1): 15724. doi:10.1038/ncomms15724. http://dx.doi.org/10.1038/ncomms15724.
    Description: Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
    Keywords: Medical And Health Sciences ; Clinical Medicine ; Urology And Nephrology ; Medicin Och Hälsovetenskap ; Klinisk Medicin ; Urologi Och Njurmedicin;
    ISSN: 20411723
    E-ISSN: 20411723
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  • 10
    Keywords: Leukocytes ; Telomere ; Humans ; Carcinoma, Renal Cell ; Kidney Neoplasms ; Genetic Predisposition To Disease ; Odds Ratio ; Risk Assessment ; Risk Factors ; Case-Control Studies ; Phenotype ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Telomere Homeostasis
    ISSN: 0302-2838
    Source: DataCite
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