共查询到20条相似文献,搜索用时 15 毫秒
1.
Kringen Pedro Wang Yun Dumeaux Vanessa Nesland Jahn M Kristensen Gunnar Borresen-Dale Anne-Lise Dorum Anne 《BMC cancer》2005,5(1):1-8
After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation.
Design
The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment.Discussion
The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers. 相似文献2.
Abnormalities in several genes are known to confer susceptibility to breast cancer. In the present study, we investigated the incidence of allelic imbalance at the BRCA1, BRCA2 and TP53 loci, in 82 sporadic breast carcinomas using a bank of highly polymorphic microsatellite markers located at the BRCA1, BRCA2 and TP53 regions. Genetic alterations were observed in 58/82 (71%) cases in at least one microsatellite marker, at one of the three regions. Twenty-seven out of 82 (33%) cases exhibited loss of heterozygosity (LOH) at BRCA1 locus while in 20/82 (34%) cases LOH was observed for the BRCA2 region. Allelic deletions were detected in 28/82 (34%) cases for the TP53 locus. Our results suggest that allelic deletion at the above genetic loci play an important role to the development of sporadic breast tumours. 相似文献
3.
Wang Y Helland A Holm R Skomedal H Abeler VM Danielsen HE Tropé CG Børresen-Dale AL Kristensen GB 《British journal of cancer》2004,90(3):678-685
We conducted the present study to evaluate the frequency and prognostic importance on long-term survival of TP53 mutations and TP53 protein accumulation in a cohort of 178 patients with early-stage ovarian carcinomas. TP53 mutations scored as aberrant temporal temperature gradient gel electrophoresis pattern from all exons were observed in 39.9% of the tumours. Full screening of exons 5-8, followed by sequencing, was successful in 135 cases, and 48 mutations altering the protein were detected in 39 cases (28.9%). TP53 mutations were slightly less common in the Federation of Gynecologists and Obstetricians stage IA than in IB/IC (P=0.05). No significant correlations with histological type, grade of differentiation, DNA ploidy status or age at diagnosis were found. TP53 protein accumulation analysed by immunohistochemistry was found in 32.6% of all tumours, and was a poor predictor of TP53 mutations with 56.4% sensitivity, 77.1% specificity, 50% positive predictive value and 81.3% negative predictive value. Neither TP53 mutations nor TP53 protein accumulation influenced the prognosis significantly in this group of patients. 相似文献
4.
Zsofia K. Stadler Emmanuel Saloustros Nichole A. L. Hansen Alice E. Schluger Noah D. Kauff Kenneth Offit Mark E. Robson 《Breast cancer research and treatment》2010,123(2):581-585
A substantial proportion of Ashkenazi Jewish (AJ) breast and ovarian cancer families carry one of three founder mutations
in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT). Non-founder mutations are identified in another 2–4% of such families. The extent to which major genomic rearrangements
in BRCA contribute to breast and ovarian cancer in the Ashkenazim is not well understood. We identified AJ individuals with breast
and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious
mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. For each proband, the pre-test probability of identifying a deleterious BRCA mutation was estimated using the Myriad II model. We identified 108 affected individuals who underwent large rearrangement
testing (80 breast cancer, 19 ovarian cancer, nine both breast and ovarian cancer). The mean estimated AJ specific pre-test
probability of a deleterious mutation in BRCA1 and BRCA2 was 24.7% (range: 4.4–88.9%). No genomic rearrangements were identified in either the entire group or in the 26 subjects
with pre-test mutation prevalence estimates exceeding 30%. Major gene rearrangements involving the BRCA1 and BRCA2 genes appear to contribute little to the burden of inherited predisposition to breast and ovarian cancer in the Ashkenazim. 相似文献
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6.
Jin Ho Kim Doo Ho Choi Dae Yeon Cho Sei Hyun Ahn Byung Ho Son Bruce G. Haffty 《Breast cancer research and treatment》2010,122(1):303-306
PALB2 is a recently discovered breast cancer susceptibility gene, and mutations in the gene have been demonstrated to confer about
twofold higher risk of breast cancer. Truncating mutations in PALB2 gene have been identified in varied populations. However, PALB2’s significance to breast cancer has not been investigated in the Korean population. In this study, we evaluated the frequency
of PALB2 1592delT and 229delT mutations in 300 Korean breast cancer patients diagnosed with either familial or early-onset breast
cancer. All patients were confirmed negative for BRCA1 and BRCA2 mutations. Neither 1592delT nor 229delT mutations was found in any of the study cohort. Our results imply that these mutations
are absent or rare in Korean patients who are negative for BRCA1 and BRCA2 mutations. We found no evidence to recommend screening for these mutations in the Korean population. However, PALB2 mutations have been demonstrated infrequent and inhomogeneous across investigated populations. Thus, screening the whole
PALB2 gene for novel mutations is required to elucidate its significance in predisposition to breast cancer in Korean women. 相似文献
7.
Christopher Schroeder Fanny Stutzmann Bernhard H. F. Weber Olaf Riess Michael Bonin 《Breast cancer research and treatment》2010,122(1):287-297
Breast cancer is the most frequent form of carcinoma in European females (incidence 65 per 100,000). In about 10% of all cases,
pedigree analysis predicts a hereditary breast-ovarian cancer syndrome (HBOC) to be causative for the disease. Frequently,
mutations in two genes, BRCA1 (Chr. 17q21) and BRCA2 (Chr. 13q12), are associated with HBOC. In females, mutations in these genes result in a lifetime risk of 80–85% for breast
cancer and 54% (BRCA1) or 23% (BRCA2) for ovarian cancer. Current genetic diagnostic tools for BRCA1 and BRCA2 remain laborious and expensive. Here, we present the first oligonucleotide resequencing microarray covering the complete
coding sequence of both genes. In total, 36 previously characterized DNAs were resequenced; all 11 patients with single-nucleotide
mutations and, due to a special mutational design, eight patients with heterozygous deletions were detected correctly. In
total, 47 different single-nucleotide variants (SNVs) were found. A newly developed software, SeqC, reduced the number of
ambiguous calls with the help of a statistical module comparing the acquired data to an online-database. SeqC improved the
average call rate to 99% (GSeq: 97%) and reduced time and efforts for manual analysis. SeqC confirmed the results obtained
by GSeq and found an additional 33 sequences changes representing 14 SNVs. In total, 945 kb were screened and the overall
turnaround time for each patient took approximately 3 days, including analysis. 相似文献
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10.
A Dørum P Møller E.J Kamsteeg H Scheffer M Burton K.R Heimdal L.O Mæhle E Hovig C.G Tropé A.H van der Hout M.A van der Meulen C.H.C.M Buys G.J te Meerman 《European journal of cancer (Oxford, England : 1990)》1997,33(14):2390-2392
We searched for a founder mutation in a population from one geographic region of Norway with prevalent breast/ovarian cancer families. We sampled 33 breast/ovarian cancer families and determined haplotypes of four markers linked to the BRCA1 region. Of the affected 33 index women, 13 (39.4%) shared one haplotype. In five (15% of total), an identical mutation was indicated by an abnormal truncated protein test (PTT) of exon 11 and shown to represent a 1675delA mutation. In the other index women, PTT of exon 11 showed no abnormality. No other BRCA1 founder mutation of this prevalence is likely because no other haplotype was more frequent in affecteds than in controls. All families with the 1675delA mutation in this geographic region may be considered as part of one large kindred. This allows a genotype–phenotype correlation to be precisely determined and used in genetic counselling for predictive testing within this kindred. Identification of identical haplotypes between unrelated affected individuals may be used to estimate the extent of founder effects for any mapped disease, without knowledge of the specific founder mutation. 相似文献
11.
Smith TR Liu-Mares W Van Emburgh BO Levine EA Allen GO Hill JW Reis IM Kresty LA Pegram MD Miller MS Hu JJ 《Carcinogenesis》2011,32(9):1354-1360
Defective DNA repair may contribute to early age and late stage at time of diagnosis and mutations in critical tumor suppressor genes, such as TP53 in breast cancer. Using DNA samples from 436 breast cancer cases (374 Caucasians and 62 African-Americans), we tested these associations with 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways: (i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) double-strand break repair: NBS1 E185Q and XRCC3 T241M; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A and MSH6 G39E and (iv) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q. Younger age at diagnosis (<50) was associated with ERCC2 312 DN/NN genotypes [odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.10, 2.81] and NBS1 185 QQ genotype (OR = 3.09; 95% CI = 1.47, 6.49). The XPC 939 QQ genotype was associated with TP53 mutations (OR = 5.80; 95% CI = 2.23, 15.09). There was a significant trend associating younger age at diagnosis (<50) with increasing numbers of risk genotypes for ERCC2 312 DN/NN, MSH6 39 EE and NBS1 185 QQ (P(trend) < 0.001). A similar significant trend was also observed associating TP53 mutations with increasing numbers of risk genotypes for XRCC1 399 QQ, XPC 939 QQ, ERCC4 415 QQ and XPC 499 AA (P(trend) < 0.001). Our pilot data suggest that nsSNPs of multiple DNA repair pathways are associated with younger age at diagnosis and TP53 mutations in breast cancer and larger studies are warranted to further evaluate these associations. 相似文献
12.
卵巢癌患者血清DNA BRCA1/TP53基因杂合性丢失的研究 总被引:2,自引:0,他引:2
目的 通过对卵巢癌患者血清DNA及其相应肿瘤组织DNA的BRCA1/TP5 3等位基因杂合性丢失 (LossofHeterozy gosity ,LOH)的研究 ,探讨上述基因变异与卵巢癌发生发展之间的相关性。方法 采用PCR并结合二核苷酸 (CA)n重复序列多态性的方法 ,分别对 76例卵巢癌 (其中 17例伴有匹配新鲜手术标本 )及 10例卵巢良性肿瘤患者的血清DNA中 4个微卫星标志BRCA1(D17S5 79、D17S85 5 )和TP5 3(TP5 3、D17S786 )进行LOH检测。结果 17对卵巢癌血清DNA与相应肿瘤组织DNA中BRCA1/TP5 3LOH发生频率之间存在明显的相关性 (P <0 .0 5 )。在 76例血清DNA标本中 5 9例 (77.6 % )至少存在一个位点LOH ,以及 4 3例 (5 6 .6 % )可出现两个以上位点LOH ,而 10例良性肿瘤患者血清DNA均未发现LOH。卵巢癌患者血清DNA中上述基因杂合性丢失频率以及所累及的微卫星位点的数目与FIGO分期呈正相关。结论 本文结果提示卵巢癌患者血清DNA与肿瘤组织DNA中BRCA1及TP5 3基因LOH密切相关 ,从而证实了卵巢癌患者血清DNA主要来源于原发肿瘤组织。鉴于血清BRCA1/TP5 3LOH与卵巢癌恶性程度相关 ,故检测卵巢癌患者血清DNABRCA1/TP5 3等位基因LOH有望作为一种反映癌症患者分期及预后的分子标记。 相似文献
13.
OBJECTIVE: The purpose of this study was to determine whether two mutations detected frequently in a population of breast and/or ovarian cancer families originating from the northeastern part of France could be due to a founder effect. METHODS: 83 index cases of families ascertained to have a familial breast and/or ovarian cancer history, were screened for mutations in all coding exons of the BRCA1 gene, using combined DGGE and direct sequencing. For haplotype analysis, six polymorphic markers were used for allelotyping of mutation carriers and non carriers from nine families with 3600del11 mutation and four families with G1710X mutation. RESULTS: Of 83 index cases, 27 (32%) had 14 different BRCA1 mutations, one of which (G1710X), had not been reported in other populations. Two mutations were particularly common: 3600del11 in exon 11 accounted for 37% and the nonsense mutation G1710X in exon 18 for 15% of all mutations. We identified a common haplotype for each mutation suggesting a common founder for each recurrent mutation. No specific phenotype could be assigned to any of the common mutations. CONCLUSIONS: These data demonstrate geographical clustering and suggest a founder effect for particular BRCA1 mutations, which identification will facilitate carrier detection in French families with breast cancer and breast and/or ovarian cancer. 相似文献
14.
Helland A Kraggerud SM Kristensen GB Holm R Abeler VM Huebner K Borresen-Dale AL Lothe RA 《International journal of cancer. Journal international du cancer》2000,88(2):217-222
Chromosome arm 3p is re-arranged in many tumor types, including cervical carcinomas. Putative tumor-suppressor genes on 3p have been proposed, including the FHIT gene, which maps to chromosome band 3p14.2. We have analyzed 79 primary cervical carcinomas for allelic imbalance (AI) at 17 chromosome 3 loci, including 3 within the FHIT gene. Expression of the FHIT gene was evaluated after immunohistochemistry with an antibody against the pFHIT protein. Previously determined human papillomavirus status, defined after in situ hybridization, showed type 16 or 18 in 56/77 tumors. Tumors were also analyzed for AI at loci within the RB1 (chromosome band 13q14.2) and the TP53 (17p13) genes for AI. AI was found at 1 or more 3p loci in 50/79 tumors, at frequencies ranging from 30% to 52% at the individual loci. Two smallest regions of overlapping deletion (SROs) were found, 1 including parts of the FHIT gene (SRO flanked by D3S1481 and D3S1313) and another more distal SRO between D3S32 and D3S1286. FHIT protein expression was reduced in 57/69 (83%) tumors but not associated with AI at FHIT loci (p = 0.56). AI was found in TP53 and RB1 in 18% and 29% of the samples, respectively. Relapse-free survival was associated with AI in the TP53 gene in both a univariate (p = 0.0003) and a multivariate (p = 0.004) analysis. This study confirms a high frequency of AI at chromosome arm 3p in primary cervical carcinomas. The AI results and the reduced FHIT protein staining indicate that FHIT alterations are important in cervical carcinogenesis. 相似文献
15.
Qinghua Wu Ragnhild A Lothe Terje Ahlquist Ilvars Silins Claes G Tropé Francesca Micci Jahn M Nesland Zhenhe Suo Guro E Lind 《Molecular cancer》2007,6(1):45
Background
The epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52) and their in vitro models (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3) by methylation-specific polymerase chain reaction (MSP). Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features. 相似文献16.
Katarina Zavodna Tomas Krivulcik Maria Gerykova Bujalkova Tomas Slamka David Martinicky Denisa Ilencikova Zdena Bartosova 《BMC cancer》2009,9(1):405
Background
Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (MMR) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. 相似文献17.
目的:评价卵巢癌P-糖蛋白、P53、P185表达对近期化疗效果的影响及相互关系。方法:免疫组织化学ABC法检测49例卵巢癌P-糖蛋白、GST-π、P53、P185表达。结果:1.卵巢癌P-糖蛋白、GST-π、P53、P185表达阳性者的近期化疗有效率分别为14.3%。27.3%、41、67%、24、63%,而表达阴性者的近期化疗有效率分别为53.6%(P0.05)、75.0%(P<0.005)。2.P-糖蛋白、P185的表达存在相关性(P<0.05)。结论:卵巢癌P-糖蛋白、GST-π、P185的表达明显影响其近期化疗效果。P-糖蛋白、P185表达的相关性值得进一步研究。 相似文献
18.
Margaret Wrensch Alex McMillan John Wiencke Joe Wiemels Karl Kelsey Joe Patoka Hywel Jones Victoria Carlton Rei Miike Jennette Sison Michelle Moghadassi Michael Prados 《Clinical cancer research》2007,13(1):197-205
PURPOSE: Our aim was to discover possible inherited factors associated with glioblastoma age at diagnosis and survival. Although new genotyping technologies allow greatly expanded exploration of such factors, they pose many challenges. EXPERIMENTAL DESIGN: In this pilot study, we (a) genotyped 112 newly diagnosed glioblastoma patients ascertained through a population-based study (group 1) with the ParAllele assay panel of approximately 10,000 nonsynonymous coding single-nucleotide polymorphisms (SNP), (b) used several statistical and bioinformatic techniques to identify 17 SNPs potentially related to either glioblastoma age at diagnosis or survival, and (c) genotyped 16 of these SNPs using conventional PCR methods in an independent group of 195 glioblastoma patients (group 2). RESULTS: In group 2, only one of the 16 SNPs, rs8057643 (located on 16p13.2), was significantly associated with glioblastoma age at diagnosis (nominal P = 0.0017; Bonferroni corrected P = 0.054). Median ages at diagnosis for those with 0, 1, or 2 T alleles were 66, 57, and 59 years in group 1 and 64, 57, and 55 years in group 2 (combined P = 0.001). Furthermore, Cox regression analyses of time to death with number of T alleles adjusted for gender and patient group yielded a hazard ratio of 0.82 (95% confidence interval, 0.68-0.98; P = 0.03). CONCLUSIONS: Although limited by a relatively small sample size, this pilot study, using well-characterized, unambiguous disease characteristics, illustrates the necessity of independent replication owing to the likelihood of false positives. Several other challenges are discussed, including attempts to incorporate information on the potential functional importance of SNPs in genome-disease association studies. 相似文献
19.
Hong S Bardwell WA Natarajan L Flatt SW Rock CL Newman VA Madlensky L Mills PJ Dimsdale JE Thomson CA Hajek RA Chilton JA Pierce JP 《Breast cancer research and treatment》2007,103(2):225-232
Background Physical activity levels among breast cancer survivors are typically low, and knowledge of the correlates of increased physical
activity among cancer survivors is limited. The purpose of this study was to examine factors that are associated with physical
activity or inactivity among breast cancer survivors.
Methods Data from 3088 women participating in the Women’s Healthy Eating and Living (WHEL) Study, collected prior to randomization,
were the focus of the current analyses. Self-reports of physical activity levels, quality of life, depression, and dietary
intakes were collected. Pearson correlation analyses were employed to examine the associations among these variables, and
multiple regression analyses were performed to examine the relationship between selected health behaviors and physical activity
levels, after controlling for demographic, breast cancer-related, and psychosocial variables.
Results Demographic and psychosocial variables were related to physical activity levels (P < 0.001 for all). Cancer treatment type and cancer stage were correlated with survivors’ physical activity levels (P < 0.01), but the associations were no longer significant after controlling for demographic variables. Physical activity levels
were strongly associated with other health behaviors, especially dietary intakes (P < 0.001), even after controlling for demographic, cancer-related, and psychosocial factors.
Conclusion Low physical activity levels in breast cancer survivors are associated with specific behavioral and other factors, which can
be considered as indicators of women at higher risk. Findings of significant differences in physical activity levels based
on demographic characteristics suggest the importance of promoting physical activity particularly among breast cancer survivors
of ethnic minority or lower education levels. 相似文献
20.
Konstantopoulou I Rampias T Ladopoulou A Koutsodontis G Armaou S Anagnostopoulos T Nikolopoulos G Kamakari S Nounesis G Stylianakis A Karanikiotis C Razis E Gogas H Keramopoulos A Gaki V Markopoulos C Skarlos D Pandis N Bei T Arzimanoglou I Fountzilas G Yannoukakos D 《Breast cancer research and treatment》2008,107(3):431-441
127 Greek breast/ovarian cancer families were screened for germline BRCA1/2 mutations by dHPLC followed by direct sequencing. Our results indicated 16 and 5 breast/ovarian cancer families bearing deleterious
mutations in the BRCA1 and BRCA2 genes, respectively. Two novel BRCA2 germline mutations (G4X and 3783del10) are reported here for the first time. Subsequent compilation of our present findings
with previously reported mutation data reveals that in a total of 287 Greek breast/ovarian cancer families, 46 and 13 carry
a deleterious mutation in BRCA1 and BRCA2, respectively. It should be noted that two BRCA1 mutations, 5382insC and G1738R, both located in exon 20, account for 46% of the families found to carry a mutation. Based
on our mutation analysis results, we propose here a hierarchical, cost-effective BRCA1/2 mutation screening protocol for individuals of Greek ethnic origin. The suggested protocol can impact on the clinical management
of breast-ovarian cancer families on a national healthcare system level.
Irene Konstantopoulou and Theodore Rampias equally contributed to this work. 相似文献