To determine whether platinum-DNA adducts and/or mRNA expression of the excision nuclease excision repair cross-complementation group 1 (ERCC1) from peripheral blood leukocytes (PBL) were associated with clinical outcome in women with epithelial ovarian cancer (EOC), participants that had previously untreated, optimally resected, stage III EOC were randomized to paclitaxel plus cisplatin or carboplatin. DNA and RNA were extracted from PBLs collected 20 to 28 h post-drug infusion. DNA adducts were measured by atomic absorption spectroscopy. ERCC1 expression was evaluated by reverse transcription-PCR. There were 170 cases fully evaluable for DNA adducts and ERCC1 mRNA expression. Adduct levels ranged from 0.43 to 131 fmol platinum/microg DNA in 140 samples; and adducts were not detectable in 30 samples. ERCC1 mRNA was detectable in 132 samples and undetectable in 38. ERCC1 mRNA expression in PBLs was not associated with any clinical end point measured. The presence of detectable versus undetectable adducts was associated with longer median progression-free survival (20.4 versus 15.6 months; P = 0.084) and overall survival (60.3 versus 36.3 months; P = 0.029), respectively. Unadjusted Cox regression modeling indicated a trend toward a reduced risk of disease progression [hazard ratio (HR), 0.686; 95% confidence interval (95% CI), 0.447-1.054; P = 0.086] and a statistically significant reduction in the risk of death (HR, 0.607; 95% CI, 0.385-0.958; P = 0.032) for women with detectable versus undetectable adducts. After adjusting for clinicopathologic variables, detectable adducts were not an independent predictor of progression-free survival or overall survival. The presence of platinum-DNA adducts, but not ERCC1 mRNA expression, in PBLs was associated with better survival, but was not an independent predictor of clinical outcome in optimal advanced EOC.

This study aimed to assess the utility of a standardised risk information tool with respect to the uptake of screening activities administered to an accessible population of first-degree relatives of patients with sporadic colorectal cancer.

The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systematically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power.

Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known.

Polymorphisms within the P1 isoenzyme of GST (GSTP1) are associated with alterations in enzyme activity and may change sensitivity to platinum-based chemotherapy. We investigated the relationship between exon 5 and exon 6 GSTP1 gene polymorphisms and treatment response, hematological, and nonhematological toxicity and overall survival for patients receiving platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC).

The epidermal growth factor receptor (EGFR) has been implicated in tumor growth and progression. Intron 1 of the EGFR gene contains a polymorphic simple sequence repeat (SSR) of 14 to 21 CA dinucleotides, the length of which correlates inversely with the level of EGFR transcription. The authors hypothesized that a shorter length of tumor SSR would be associated with poorer survival in patients with non-small cell lung cancer (NSCLC).

Hyperdiploid multiple myeloma (H-MM) is the most common form of myeloma. In this gene expression profiling study, we show that H-MM is defined by a protein biosynthesis signature that is primarily driven by a gene dosage mechanism as a result of trisomic chromosomes. Within H-MM, four independently validated patient clusters overexpressing nonoverlapping sets of genes that form cognate pathways/networks that have potential biological importance in multiple myeloma were identified. One prominent cluster, cluster 1, is characterized by high expression of cancer testis antigen and proliferation-associated genes. Tumors from these patients were more proliferative than tumors in other clusters (median plasma cell labeling index, 3.8; P < 0.05). Another cluster, cluster 3, is characterized by genes involved in tumor necrosis factor/nuclear factor-kappaB signaling and antiapoptosis. These patients have better response to bortezomib as compared with patients within other clusters (70% versus 29%; P = 0.02). Furthermore, for a group of patients generally thought to have better prognosis, a cluster of patients with short survival (cluster 1; median survival, 27 months) could be identified. This analysis illustrates the heterogeneity within H-MM and the importance of defining specific cytogenetic prognostic factors. Furthermore, the signatures that defined these clusters may provide a basis for tailoring treatment to individual patients.

Barrett's esophagus is a premalignant condition that is a risk factor for the development of esophageal adenocarcinoma, a disease whose incidence is rapidly increasing. Because aspirin and other nonsteroidal anti-inflammatory drugs, such as celecoxib, may decrease the risk of developing esophageal cancer, we investigated the effect of long-term administration of celecoxib in patients with Barrett's esophagus with dysplasia.

Preclinical data indicate that p-53 gene mutations predict resistance to doxorubicin (A) but not to docetaxel (Taxotere) (T). In the TAX 303 trial, A and T have been compared with advanced breast cancer patients.

Mutations in the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity of non-small cell lung cancer (NSCLC) to gefitinib, an EGFR tyrosine kinase inhibitor. The objective of this study was to prospectively evaluate the efficacy of gefitinib in patients with stage III/IV NSCLC whose tumors carried EGFR mutations, irrespective of previous chemotherapy.

The objective of this study was to assess the efficacy of adding chronic, intermittent, low-dose vinorelbine to gefitinib treatment for patients who had adenocarcinoma of the lung who failed>or=2 regimens of chemotherapy.

Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance (MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault protein (MVP), and the breast cancer resistance protein (BCRP/ABCG2). The clinical value of MDR1, MRP1, LRP/MVP, and BCRP messenger RNA (mRNA) expression was prospectively studied in 154 newly diagnosed AML patients >or=60 years who were treated in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count (respectively, p < 0.05, p < 0.001, p < 0.001 and p < 0.001). Higher BCRP mRNA was associated with secondary AML (p < 0.05). MDR1 and BCRP mRNA were highly significantly associated (p < 0.001), as were MRP1 and LRP mRNA (p < 0.001) expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1/BCRP coexpression, were associated with a lower complete response (CR) rate and with worse event-free survival and overall survival. When adjusted for other prognostic actors, only CD34-related MDR1/BCRP coexpression remained significantly associated with a lower CR rate (p = 0.03), thereby identifying a clinically resistant subgroup of elderly AML patients.

Family history is one the greatest risk factors for disease and one of the most important informational tools in medical genetics for the purpose of diagnosis, risk assessment, prevention and treatment. However, research is needed on the comparability of different methods of cancer family history assessment and the influence of psychosocial factors in family history reports. The purpose of this study was to determine if individuals had discrepancies between written and interview reports of cancer family history and the role of psychosocial factors in these discrepancies. Oncology patients (n=104) were administered a survey to assess psychosocial factors (i.e., information-seeking, worry, perceived risk, and health literacy) and were asked to provide family history in a written and an interview form. Randomization determined which form individuals received first. No differences in the amount of missing data or the amount of unspecified data were noted between the written and interview method. Psychosocial factors did not differentiate between those who had discrepancies in family history reports and those who did not have discrepancies in family history reports; although there was a trend for those with lower literacy and those who were blunters to be more discrepant on type of cancer diagnosis. In sum, this preliminary study indicates that written and interview methods of family history assessment for first degree relatives may be used interchangeably. The ability to use written methods will facilitate collection of basic family history information in the oncology clinic.

Individuals undergoing cancer genetic risk assessment have been found to have a poor understanding of the process, which may affect how well they cope with learning their risk. This paper reports free-text data from questionnaires completed by women undergoing a randomised controlled trial of a psychological intervention. Of the 268 women undergoing genetic assessment for familial breast/ovarian cancer risk who were invited to take part in the trial, 157 women returned research questionnaires. Of these, 97 women provided free-text comments upon referral to a cancer genetics clinic, 62 provided comments whilst waiting for risk information (average, moderate or high), and 36 women provided comments following notification of risk. This paper reports a thematic analysis of the free-text data. Themes reflected individuals' poor knowledge and uncertainty about genetic risk assessment. How well individuals responded to learning their risk depended upon whether expectations had been met. Regardless of risk, individuals undergoing cancer genetic risk assessment are likely to benefit from increased information about its process and timescales, and access to increased psychological support. Free-text comments can provide valuable data about individuals' expectations and knowledge of genetics services.

Expression of Bcl-2 protein is associated with chemotherapy resistance and decreased survival in chronic lymphocytic leukemia (CLL). We evaluated whether oblimersen would improve response to chemotherapy in patients with relapsed or refractory CLL.

Magnetic resonance imaging (MRI) permits the detection of diffuse and focal bone marrow infiltration in the absence of osteopenia or focal osteolysis on standard metastatic bone surveys (MBSs).

Genomic features including unmutated immunoglobulin variable region heavy chain (IgVH) genes, del(11q22.3), del(17p13.1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome.

Base excision repair (BER) corrects DNA damage caused by oxidative stress and low folate intake, which are putative risk factors for colorectal neoplasia. To examine the relationship between genetic variation in BER genes and colorectal adenoma risk, we conducted a case-control study of 767 cases of advanced colorectal adenoma and 773 controls from the baseline screening exam of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cases included participants diagnosed with advanced left-sided adenoma, and controls were subjects without evidence of a left-sided polyp by sigmoidoscopy, frequency-matched to cases on race and gender. Twenty single nucleotide polymorphisms were genotyped in four BER genes (APEX1, PARP1, POLB, and XRCC1), and conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association with colorectal adenoma. Two variants with possible functional significance were associated with risk. The APEX1 51H variant was associated with a borderline significant decreased risk of colorectal adenoma (OR, 0.66; 95% CI, 0.44-1.00), and the XRCC1 399Q variant was inversely associated with risk among Caucasians (OR, 0.80; 95% CI, 0.64-0.99). Homozygotes at two PARP1 loci (A284A and IVS13+118G>A) were also associated with a decreased risk of colorectal adenoma compared with wild-type carriers (OR, 0.70; 95% CI, 0.49-0.98 for both), which was restricted to advanced adenomas displaying histologically aggressive characteristics (OR, 0.51; 95% CI, 0.33-0.78, P = 0.002 for PARP1 A284A). This study suggests that polymorphisms in APEX1, XRCC1, and PARP1 may be associated with advanced colorectal adenoma.

Rarely has utilization of genetic counseling for Hereditary Breast and Ovarian Cancer (HBOC) been studied separately from utilization of testing. At Kaiser Permanente Colorado, consistently only 30% of all members referred for HBOC attend genetic counseling. To increase the volume of genetic counseling appointments, a patient navigator approach was pilot tested in a randomized-controlled trial over 3 months. A total of 125 members were referred for HBOC genetic counseling (55 randomized to PN, 70 randomized to usual care). Utilization of referrals for Navigator-assisted members was 44%, compared to 31% in the usual care arm (p=0.16). The patient navigator significantly decreased time to appointment, with over 80% of Navigator-assisted members seen for genetic counseling less than three months from referral date, compared to 32% in usual care (p=0.002). patient navigator assistance shortens time from referral to appointment for HBOC genetic counseling, and may increase utilization of such services.

The objective of this study was to identify the molecular processes responsible for the anti-lesional activity of imiquimod in subjects with actinic keratosis using global gene expression profiling.