Inequalities in cancer screening participation: examining differences in perceived benefits and barriers.

OBJECTIVE: Inequalities exist in colorectal cancer (CRC) screening uptake, with people from lower socioeconomic status backgrounds less likely to participate. Identifying the facilitators and barriers to screening uptake is important to addressing screening disparities. We pooled data from 2 trials to examine educational differences in psychological constructs related to guaiac fecal occult blood testing. METHODS: Patients (n = 8576) registered at 7 general practices in England, within 15 years of the eligible age range for screening (45-59.5 years), were invited to complete a questionnaire. Measures included perceived barriers (emotional and practical) and benefits of screening, screening intentions, and participant characteristics including education. RESULTS: After data pooling, 2181 responses were included. People with high school education or no formal education reported higher emotional and practical barriers and were less likely to definitely intend to participate in screening, compared with university graduates in analyses controlling for study arm and participant characteristics. The belief that one would worry more about CRC after screening and concerns about tempting fate were strongly negatively associated with education. In a model including education and participant characteristics, respondents with low emotional barriers, low practical barriers, and high perceived benefits were more likely to definitely intend to take part in screening. CONCLUSIONS: In this analysis of adults approaching the CRC screening age, there was a consistent effect of education on perceived barriers toward guaiac fecal occult blood testing, which could affect screening decision making. Interventions should target specific barriers to reduce educational disparities in screening uptake and avoid exacerbating inequalities in CRC mortality.

Phase I dose escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors.

PURPOSE: This phase I study endeavored to estimate the maximum tolerated dose and describe the dose-limiting toxicities (DLTs) of oral irinotecan with gefitinib in children with refractory solid tumors. METHODS: Oral irinotecan was administered on days 1-5 and 8-12 with oral gefitinib (fixed dose, 150 mg/m(2)/day) on days 1-12 of a 21-day course. The escalation with overdose control method guided irinotecan dose escalation (7 dose levels, range 5-40 mg/m(2)/day). RESULTS: Sixteen of 19 patients were evaluable, with serial pharmacokinetic studies in ten patients. Diagnoses included osteosarcoma (N = 5), neuroblastoma (N = 3), sarcoma (N = 3), and others (N = 5). Patients received a median of two courses (range 1-20), with at least two patients treated on dose levels 2-7. Three patients had five DLTs; the most common being metabolic (hypokalemia, N = 2 and hypophosphatemia, N = 1) at dose levels two (10 mg/m(2)) and four (20 mg/m(2)). One patient experienced grade 3 diarrhea (40 mg/m(2)). Irinotecan bioavailability was 2.5-fold higher when co-administered with gefitinib, while the conversion rate of irinotecan to SN-38 lactone was unaffected. The study closed due to poor accrual before evaluation of the next recommended irinotecan dose level (35 mg/m(2)). Of 11 patients receiving at least two courses of therapy, three had stable disease lasting two to four courses and one patient maintained a complete response through 18 courses. CONCLUSIONS: The combination of oral gefitinib and irinotecan has acceptable toxicity and anti-tumor activity in pediatric patients with refractory solid tumors. Pharmacokinetic analysis confirms that co-administration of gefitinib increases irinotecan bioavailability leading to an increased SN-38 lactone systemic exposure.

Follicle-derived thyroid cancer in young people: the Duke experience.

Follicle-derived thyroid cancer is rare in the young. The authors examined a population with a low rate of radiation exposure and who were treated at a single institution. The records of 56 patients diagnosed before the age of 25 years were analyzed. The majority of patients presented with an asymptomatic thyroid mass. All patients were treated surgically and half received postoperative ablation with 131I. Recurrent disease was detected in 29%. The presence of local metastases at initial surgery was a predictor of recurrence. No patient presented with distant metastases and no patient died of thyroid cancer. Although radiation exposure remains a risk factor for thyroid cancer in the young, only a minority of patients with thyroid cancer have a known history of exposure. Patients who are diagnosed at a young age have a high rate of long-term recurrence, and should be followed closely throughout their lives.

K-ras and p53 in pancreatic cancer: association with medical history, histopathology, and environmental exposures in a population-based study.

Pancreatic cancer is a highly fatal cancer with few identified risk factors. Increased risk of pancreatic cancer in tobacco smokers and among diabetic patients is well established, and some reports have suggested associations with coffee consumption and occupational exposure to organochlorines. At present, there is little information regarding the possible association of these risk factors with the known genetic alterations found in pancreatic cancers, such as activation of the K-ras oncogene and inactivation of the p53 tumor suppressor gene. Knowledge of such relationships may help to understand the molecular pathways of pancreatic tumorigenesis. We investigated the association between these molecular defects and risk factors for pancreatic cancer in 61 newly diagnosed patients identified through an ongoing study of pancreatic cancer in the San Francisco Bay Area. Interview information was obtained regarding environmental exposures, medical history, and demographic factors. Serum levels of dichlorodiphenyltrichloroethylene (DDE) and polychlorinated biphenyls were available on a subset of 24 patients. Tumor blocks were located from local hospitals and used for K-ras mutational analysis at codon 12 and for p53 protein immunohistochemistry. The molecular analyses were facilitated through the use of laser capture microdissection, which provides a reliable method to obtain almost pure populations of tumor cells. Mutations in K-ras codon 12 were found in 46 (75%) of 61 pancreatic cancers. A prior diagnosis of diabetes was significantly associated with K-ras negative tumors (P = 0.002, Fisher's exact test). The absence of this mutation was also associated with increased serum levels of DDE, although this association was not statistically significant (P = 0.16, Wilcoxon's test). There was no difference in polychlorinated biphenyl levels between the K-ras wild-type and mutant groups. Immunohistochemical staining for p53 protein did not differ by patient characteristics or clinical history, but significant associations were found with poor glandular differentiation (P = 0.002, chi2 trend test), severe nuclear atypia (P = 0.0007, chi2 trend test), and high tumor grade (P = 0.004, chi2 trend test). Our results are suggestive of the presence of K-ras codon 12 mutation-independent tumorigenesis pathways in patients with prior diabetes and possibly in patients with higher serum levels of DDE. Our results also support a role for the p53 tumor suppressor protein in the maintenance of genomic integrity.

Papillary adenocarcinoma of the thyroid in a thyroglossal duct cyst.

A case report is presented of an 8-year-old boy who underwent resection of a thyroglossal duct cyst to illustrate a rare, but significant, complication of a common clinical problem. Pathological examination revealed that it contained a papillary adenocarcinoma of the thyroid, presumably arising from ectopic glandular tissue in the cyst. Thyroglossal duct cysts are a common cause of midline neck masses in children. Occult thyroid carcinoma is a rare co-morbid finding. It infrequently leads to death, but thyroglossal duct cysts may also contain the only functioning, albeit ectopic, thyroid tissue. Patients with clinical thyroglossal duct cysts should be carefully evaluated preoperatively for the presence of tumor and other functioning thyroid tissue prior to excision of the cyst.

Roles of trk family neurotrophin receptors in medullary thyroid carcinoma development and progression.

Although initiating mutations in the ret protooncogene have been found in familial and sporadic medullary thyroid carcinoma (MTC), the molecular events underlying subsequent tumor progression stages are unknown. We now report that changes in trk family neurotrophin receptor expression appear to be involved in both preneoplastic thyroid C cell hyperplasia and later tumor progression. Only a subset of normal C cells expresses trk family receptors, but, in C cell hyperplasia, the affected cells consistently express trkB, with variable expression of trkA and trkC. In later stages of gross MTC tumors, trkB expression was substantially reduced, while trkC expression was increased and often intense. In a cell culture model of MTC, exogenous trkB expression resulted in severely impaired tumorigenicity and was associated with 11-fold lower levels of the angiogenesis factor vascular endothelial growth factor. These results suggest that trk family receptor genes participate in MTC development and progression, and, in particular, that trkB may limit MTC tumor growth by inhibition of angiogenesis.

Expression and function of Trk-C in favourable human neuroblastomas.

Human neuroblastomas express the neurotrophin receptors trk-A and trk-B. Favourable outcome is associated with expression of trk-A, while unfavourable, MYCN amplified tumours express trk-B. In this study we examined the expression of trk-C in primary neuroblastoma tumour-derived cell lines. We found by Northern blot analysis that trk-C mRNA is expressed in 14 of 55 (25%) primary tumours. Trk-C was expressed in significantly more lower stage tumours (stage 1, 2, 4S) than higher stage tumours (stage 3, 4, P < 0.04). The expression of trk-C was correlated positively with survival and negatively correlated with MYCN amplification. We also studied the function of trk-C in transfected cell lines and found that NT-3 promotes both cell survival and differentiation. Our results suggest that trk-C is involved in the biology of favourable neuroblastomas.

Molecular cloning of the cDNA for human TrkC (NTRK3), chromosomal assignment, and evidence for a splice variant.

TrkC is a receptor tyrosine kinase that is activated by neurotrophin-3, a factor important in the development of certain areas of the central nervous system. We have cloned and sequenced the human trkC cDNA and found that the predicted amino acid sequence is 97 to 98% homologous to the rat and porcine trkC sequences, respectively. The rat trkC has several isoforms due to alternative splicing in the tyrosine kinase domain. We cloned one human splice variant that has a nucleic acid sequence identical to the rat isoform with an insert of 14 amino acids. The human trkC cDNA also has a (CGG)n repeat in the 5'-untranslated region. This sequence was not highly polymorphic in that 79 of 80 chromosomes examined had eight repeats, while 1 chromosome had four repeats. By PCR analysis of a somatic cell hybrid panel and fluorescence in situ hybridization with the cDNA clone, human trkC was mapped to chromosome 15q24-q25.

Cytomegalovirus homologs of cellular G protein-coupled receptor genes are transcribed.

The genome of human cytomegalovirus (HCMV) contains three genes with homology to cellular G protein-coupled receptors (GCRs). Evidence is presented here that all three HCMV GCR genes are transcribed during infection, that they are transcribed as two sets of 3'-coterminal mRNAs, and that their transcription is restricted to the late phase of infection.