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1.
Ho JW Choi SC Lee YF Hui TC Cherny SS Garcia-Barceló MM Carvajal-Carmona L Liu R To SH Yau TK Chung CC Yau CC Hui SM Lau PY Yuen CH Wong YW Ho S Fung SS Tomlinson IP Houlston RS Cheng KK Sham PC 《British journal of cancer》2011,104(2):369-375
Background:
Recent genome-wide association studies of colorectal cancer (CRC) have identified common single-nucleotide polymorphisms (SNPs) mapping to 10 independent loci that confer modest increased risk. These studies have been conducted in European populations and it is unclear whether these observations generalise to populations with different ethnicities and rates of CRC.Methods:
An association study was performed on 892 CRC cases and 890 controls recruited from the Hong Kong Chinese population, genotyping 32 SNPs, which were either associated with CRC in previous studies or are in close proximity to previously reported risk SNPs.Results:
Twelve of the SNPs showed evidence of an association. The strongest associations were provided by rs10795668 on 10p14, rs4779584 on 15q14 and rs12953717 on 18q21.2. There was significant linear association between CRC risk and the number of independent risk variants possessed by an individual (P=2.29 × 10−5).Conclusion:
These results indicate that some previously reported SNP associations also impact on CRC risk in the Chinese population. Possible reasons for failure of replication for some loci include inadequate study power, differences in allele frequency, linkage disequilibrium structure or effect size between populations. Our results suggest that many associations for CRC are likely to generalise across populations. 相似文献2.
J Sullivan R Kopp K Stratton C Manschreck M Corines R Rau-Murthy J Hayes A Lincon A Ashraf T Thomas K Schrader D Gallagher R Hamilton H Scher H Lilja P Scardino J Eastham K Offit J Vijai R J Klein 《British journal of cancer》2015,113(1):166-172
Background:
Genome-wide association studies have identified multiple single-nucleotide polymorphsims (SNPs) associated with prostate cancer (PCa). Although these SNPs have been clearly associated with disease risk, their relationship with clinical outcomes is less clear. Our aim was to assess the frequency of known PCa susceptibility alleles within a single institution ascertainment and to correlate risk alleles with disease-specific outcomes.Methods:
We genotyped 1354 individuals treated for localised PCa between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to phenotypic data. We investigated associations between 61 SNPs and disease-specific end points using multivariable analysis and also determined if SNPs were associated with PSA at diagnosis.Results:
Seven SNPs showed associations on multivariable analysis (P<0.05), rs13385191 with both biochemical recurrence (BR) and castrate metastasis (CM), rs339331 (BR), rs1894292, rs17178655 and rs11067228 (CM), and rs11902236 and rs4857841 PCa-specific mortality. After applying a Bonferroni correction for number of SNPs (P<0.0008), the only persistent significant association was between rs17632542 (KLK3) and PSA levels at diagnosis (P=1.4 × 10−5).Conclusions:
We confirmed that rs17632542 in KLK3 is associated with PSA at diagnosis. No significant association was seen between loci and disease-specific end points when accounting for multiple testing. This provides further evidence that known PCa risk SNPs do not predict likelihood of disease progression. 相似文献3.
Antoniou AC Kuchenbaecker KB Soucy P Beesley J Chen X McGuffog L Lee A Barrowdale D Healey S Sinilnikova OM Caligo MA Loman N Harbst K Lindblom A Arver B Rosenquist R Karlsson P Nathanson K Domchek S Rebbeck T Jakubowska A Lubinski J Jaworska K Durda K Złowowcka-Perłowska E Osorio A Durán M Andrés R Benítez J Hamann U Hogervorst FB van Os TA Verhoef S Meijers-Heijboer HE Wijnen J Gómez Garcia EB Ligtenberg MJ Kriege M Collée JM Ausems MG Oosterwijk JC Peock S Frost D Ellis SD Platte R 《Breast cancer research : BCR》2012,14(1):R33
Introduction
Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).Methods
To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.Results
Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).Conclusions
The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers. 相似文献4.
B Kinnersley G Migliorini P Broderick N Whiffin SE Dobbins G Casey J Hopper;The Colon Cancer Family Registry O Sieber L Lipton DJ Kerr MG Dunlop IP Tomlinson RS Houlston 《British journal of cancer》2012,107(6):1001-1008
Background:
Polymorphic variation at the 5p15.33 (TERT–CLPTM1L) locus is associated with the risk of many cancers but a relationship with colorectal cancer (CRC) risk has yet to be defined.Methods:
We used data from six genome-wide association studies (GWAS) of CRC, linkage disequilibrium mapping and imputation, to examine the relationship between 73 single-nucleotide polymorphisms at 5p15.33 and CRC risk in detail.Results:
rs2736100, which localises to intron 2 of TERT, provided the strongest evidence of an association with CRC (P=2.28 × 10−4). The association was also shown in an independent series of 10 047 CRC cases and 6918 controls (P=0.02). A meta-analysis of all seven studies (totalling 16 039 cases, 16 430 controls) provided increased evidence of association (P=2.49 × 10−5; per allele odds ratio=1.07). The association of rs2736100 on CRC risk was shown to be independent of 15 low-penetrance variants previously identified.Conclusion:
The rs2736100 association demonstrates an influence of variation at 5p15.33 on CRC risk and further evidence that the 5p15.33 (TERT–CLPTM1L) locus has pleiotropic effects (reflecting generic or lineage-specific effects) on cancer risk. 相似文献5.
Burley VJ Greenwood DC Hepworth SJ Fraser LK de Kok TM van Breda SG Kyrtopoulos SA Botsivali M Kleinjans J McKinney PA Cade JE 《British journal of cancer》2010,103(11):1749-1754
Background:
No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide.Methods:
A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33 731 women aged 35–69 years from the UK Women''s Cohort Study followed up for a median of 11 years.Results:
In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day−1, 95% CI: 0.98–1.18, Ptrend=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0–1.3, Ptrend=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9–1.1, Ptrend=0.99).Conclusions:
There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation. 相似文献6.
《British journal of cancer》2009,101(12):2048-2054
Background:
In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers.Methods:
We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach.Results:
We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers.Conclusion:
This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out. 相似文献7.
Stevens KN Garcia-Closas M Fredericksen Z Kosel M Pankratz VS Hopper JL Dite GS Apicella C Southey MC Schmidt MK Broeks A Van 't Veer LJ Tollenaar RA Fasching PA Beckmann MW Hein A Ekici AB Johnson N Peto J dos Santos Silva I Gibson L Sawyer E Tomlinson I Kerin MJ Chanock S Lissowska J Hunter DJ Hoover RN Thomas GD Milne RL Arias Pérez JI González-Neira A Benítez J Burwinkel B Meindl A Schmutzler RK Bartrar CR Hamann U Ko YD Brüning T Chang-Claude J Hein R Wang-Gohrke S Dörk T Schürmann P 《British journal of cancer》2011,105(12):1934-1939
Background:
Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer.Methods:
A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC).Results:
Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95–0.99, P=4.6 × 10−3), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96–1.01, P=0.139).Conclusion:
Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer 相似文献8.
Jiang X Hiki N Nunobe S Kumagai K Kubota T Aikou S Sano T Yamaguchi T 《British journal of cancer》2012,107(2):275-279
Background:
The inflammation-based Glasgow prognostic score (GPS) has been shown to be a prognostic factor for a variety of tumours. This study investigates the significance of the modified GPS (mGPS) for the prognosis of patients with gastric cancer.Methods:
The mGPS (0=C-reactive protein (CRP)⩽10 mg l−1, 1=CRP>10 mg l−1 and 2=CRP>10 mg l−1 and albumin<35 g l−1) was calculated on the basis of preoperative data for 1710 patients with gastric cancer who underwent surgery between January 2000 and December 2007. Patients were given an mGPS of 0, 1 or 2. The prognostic significance was analysed by univariate and multivariate analyses.Results:
Increased mGPS was associated with male patient, old age, low body mass index, increased white cell count and neutrophils, elevated carcinoembryonic antigen and CA19-9 and advanced tumour stage. Kaplan–Meier analysis and log-rank test revealed that a higher mGPS predicted a higher risk of postoperative mortality in both relative early-stage (stage I; P<0.001) and advanced-stage cancer (stage II, III and IV; P<0.001). Multivariate analysis demonstrated the mGPS to be a risk factor for postoperative mortality (odds ratio 1.845; 95% confidence interval 1.184–2.875; P=0.007).Conclusion:
The preoperative mGPS is a simple and useful prognostic factor for postoperative survival in patients with gastric cancer. 相似文献9.
Background:
Genes of the adiponectin pathway are interesting candidates for colorectal cancer risk based on the potential association between colorectal cancer and obesity. However, variants of the adiponectin gene (ADIPOQ) have been demonstrated to be inconsistently associated with risk of colorectal cancer.Methods:
The current study attempted to evaluate these findings by examining several single nucleotide polymorphisms (SNPs) that were previously genotyped as part of a genome-wide association study in the ADIPOQ gene. Genotyping was also performed for a previously reported risk variant, rs266729, in 1062 individuals with a diagnosis of colorectal cancer and 1062 controls matched on age, gender and ethnicity (Jewish or not Jewish) as part of a population-based case–control study in Israel.Results:
No evidence was found for an association between ADIPOQ and risk of colorectal cancer. The single nucleotide variant previously associated with decreased risk of colorectal cancer, rs266729, revealed an adjusted odds ratio of 1.04; 95% confidence interval, 0.88–1.23.Conclusion:
The SNP, rs266729, was not strongly associated with colorectal cancer in patients of Ashkenazi Jewish descent or other ethnic groups in Israel. 相似文献10.
Background:
Obesity increases the risk of uterine cancer, but results by histological type have differed.Methods:
We followed 36 755 women for 17.8 years for uterine cancers.Results and conclusion:
Body mass index (BMI) was positively associated with uterine cancers as a whole, particularly for endometrioid adenocarcinomas, for which the relative risk for very obese women (BMI: ⩾40 kg m−2) compared with lean (BMI: 20–24 kg m−2) women, was 11.1 (95% confidence interval: 5.2–23.8). 相似文献11.
12.
Osorio A Milne RL Alonso R Pita G Peterlongo P Teulé A Nathanson KL Domchek SM Rebbeck T Lasa A Konstantopoulou I Hogervorst FB Verhoef S van Dooren MF Jager A Ausems MG Aalfs CM van Asperen CJ Vreeswijk M Waisfisz Q Van Roozendaal CE Ligtenberg MJ;HEBON;EMBRACE Easton DF Peock S Cook M Oliver CT Frost D Curzon B Evans DG Lalloo F Eeles R Izatt L Davidson R Adlard J Eccles D Ong KR Douglas F Downing S Brewer C Walker L Nevanlinna H Aittomäki K Couch FJ Fredericksen Z Lindor NM Godwin A Isaacs C 《British journal of cancer》2011,104(8):1356-1361
Background:
Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2.Methods:
Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers.Results:
An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3–34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.Conclusions and inte
No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers. 相似文献13.
Wong CS Lim GH Gao F Jakes RW Offman J Chia KS Duffy SW 《British journal of cancer》2011,104(5):871-874
Background:
Joint effects of mammographic density and other risk factors on breast cancer risk remain unclear.Methods:
From The Singapore Breast Screening Project, we selected 491 cases and 982 controls. Mammographic density was measured quantitatively. Data analysis was by conditional logistic regression.Results:
Density was a significant risk factor, adjusting for other factors. Density of 76–100% had an odds ratio of 5.54 (95% CI 2.38–12.90) compared with 0–10%. Density had significant interactions with body mass index and oral contraceptive use (P=0.02).Conclusions:
Percent density increases breast cancer risk in addition to effects of other risk factors, and modifies the effects of BMI and OCs. 相似文献14.
C-F Xu T Johnson J Garcia-Donas T K Choueiri C N Sternberg I D Davis N Bing K C Deen Z Xue L McCann E Esteban J C Whittaker C F Spraggs C Rodríguez-Antona L N Pandite R J Motzer 《British journal of cancer》2015,112(7):1190-1198
Background:
We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC).Methods:
The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N=241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N=729, study 2) and an observational study of sunitinib-treated patients (N=89, study 3).Results:
In study 1, four SNPs showed nominally significant association (P≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P≤0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P≤0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10−5; variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15–1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients.Conclusions:
Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies. 相似文献15.
V Abkevich K M Timms B T Hennessy J Potter M S Carey L A Meyer K Smith-McCune R Broaddus K H Lu J Chen T V Tran D Williams D Iliev S Jammulapati L M FitzGerald T Krivak J A DeLoia A Gutin G B Mills J S Lanchbury 《British journal of cancer》2012,107(10):1776-1782
Background:
Defects in BRCA1, BRCA2, and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of loss of heterozygosity (LOH).Methods:
Ovarian tumours from two independent data sets were characterised for defects in BRCA1, BRCA2, and RAD51C, and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines.Results:
Loss of heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 (P=10−11). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets (P=10−5 and 10−29), and identified breast and pancreatic cell lines with BRCA defects.Conclusion:
The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers. 相似文献16.
Kyle M. Walsh Terri Rice Paul A. Decker Matthew L. Kosel Thomas Kollmeyer Helen M. Hansen Shichun Zheng Lucie S. McCoy Paige M. Bracci Erik Anderson George Hsuang Joe L. Wiemels Alexander R. Pico Ivan Smirnov Annette M. Molinaro Tarik Tihan Mitchell S. Berger Susan M. Chang Michael D. Prados Daniel H. Lachance Hugues Sicotte Jeanette E. Eckel-Passow John K. Wiencke Robert B. Jenkins Margaret R. Wrensch 《Neuro-oncology》2013,15(8):1041-1047
Background
Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma.Methods
SNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between “number of risk alleles” and “age at diagnosis,” adjusted for sex and study site and stratified by tumor grade/histology where appropriate.Results
Four SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10−22 and P = 9.5 × 10−7, respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10−4 and P = 2.5 × 10−4, respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups.Conclusions
Carrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres). 相似文献17.
P N Munster D Marchion S Thomas M Egorin S Minton G Springett J-H Lee G Simon A Chiappori D Sullivan A Daud 《British journal of cancer》2009,101(7):1044-1050
Background:
Histone deacetylase inhibitors (HDACi) can sensitise cancer cells to topoisomerase inhibitors by increasing their access and binding to DNA.Methods:
This phase I trial was designed to determine the toxicity profile, tolerability, and recommended phase II dose of escalating doses of the HDACi vorinostat, with weekly doxorubicin.Results:
In total, 32 patients were treated; vorinostat was dosed at 400, 600, 800, or 1000 mg day−1 on days 1–3, followed by doxorubicin (20 mg m−2) on day 3 for 3 of 4 weeks. Maximal tolerated dose was determined to be 800 mg day−1 of vorinostat. Dose-limiting toxicities were grade 3 nausea/vomiting (two out of six) and fatigue (one out of six) at 1000 mg day−1. Non-dose-limiting grade 3/4 toxicities included haematological toxicity and venous thromboembolism. Antitumor activity in 24 evaluable patients included two partial responses (breast and prostate cancer). Two patients with melanoma had stable disease for ⩾8 months. Histone hyperacetylation changes in peripheral blood mononuclear and tumour cells were comparable. Histone hyperacetylation seemed to correlate with pre-treatment HDAC2 expression.Conclusion:
These findings suggest that vorinostat can be combined with weekly doxorubicin in this schedule at a dose of 800 mg day−1. The HDAC2 expression may be a marker predictive of HDAC inhibition. Antitumor activity of this regimen in breast cancer, prostate cancer, and melanoma seems interesting. 相似文献18.
Background:
Epoetin-β is used to treat patients with cancer undergoing chemotherapy to alleviate the symptoms of anaemia, reduce the risk of blood transfusions and improve quality of life (QoL).Methods:
This meta-analysis of all 12 randomised, controlled studies of epoetin-β evaluated the impact of therapy at different Hb-initiation levels and to different target Hb levels on overall survival, tumour progression and thromboembolic events (TEE). An analysis of risk factors pre-disposing patients to TEEs under epoetin-β therapy was also performed. A total of 2297 patients are included in the analysis.Results:
Analyses based on various Hb-initiation levels indicate no detrimental impact on survival (HR 0.99; 95% CI 0.70, 1.40) and a favourable impact on disease progression (HR 0.73; 95% CI 0.57, 0.94) when epoetin-β was used within its licensed indication (Hb initiation ⩽10 g dl−1) or the EORTC recommended level of 11 g dl−1. An increased risk of TEEs is seen for all Hb-initiation level strata and a detrimental impact on survival is seen when initiating epoetin-β therapy at Hb levels >11 g dl−1. We observe no association between high target Hb levels (⩾13 g dl−1) and an increased risk of mortality, disease progression or TEEs with epoetin-β compared with control.Conclusion:
The results of this analysis indicate that epoetin-β therapy has no detrimental impact on survival or tumour progression when initiated at Hb levels up to 11 g dl−1. Furthermore, there is no evidence to suggest that high Hb values achieved during epoetin-β therapy are associated with an increased mortality, disease progression or TEE rate. 相似文献19.
Soley Bayraktar Patricia A. Thompson Suk‐Young Yoo Kim‐anh Do Aysegul A. Sahin Banu K. Arun Melissa L. Bondy Abenaa M. Brewster 《The oncologist》2013,18(5):493-500
Background.
Several single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies (GWAS). We investigated whether eight risk SNPs identified in GWAS were associated with breast cancer disease-free survival (DFS) and overall survival (OS) rates.Patients and Methods.
A cohort of 739 white women with early-stage breast cancer was genotyped for eight GWAS-identified SNPs (rs2981582, rs1219648 [FGFR2], rs3803662, rs12443621, rs8051542 [TOX3], rs999737 [RAD51L1], rs6504950 [17q23], and rs4973768 [3p24]). Relationships between SNPs and breast cancer outcomes were evaluated using Cox proportional hazard regression models. The cumulative effects of SNPs on breast cancer outcomes were assessed by computing the number of at-risk genotypes.Results.
At a median follow-up of 121 months (range: 188–231 months) for survivors, 237 deaths (32%) and 186 breast cancer events (25%) were identified among the 739 patients. After adjusting for age, clinical stage, and treatment, rs12443621 (16q12; p = .03) and rs6504950 (17q23; p = .008) were prognostic for OS but not DFS. A higher risk for death was also found in the multivariable analysis of patients harboring three or four at-risk genotypes of the GWAS SNPs compared to patients carrying two or less at-risk genotypes (hazard ratio: 1.60, 95% confidence interval: 1.23–2.24; p = .0008).Conclusion.
The study results suggest that previously identified breast cancer risk susceptibility loci, rs12443621 (16q12) and rs6504950 (17q23), may influence breast cancer prognosis or comorbid conditions associated with overall survival. The precise molecular mechanisms through which these risk SNPs, as well as others that were not included in the analysis, influence clinical outcomes remain to be determined. 相似文献20.