Cancer detection and prevention最新文献

New oncologic treatments have improved survival in osteosarcoma and Ewing's sarcoma. However, these treatments may cause secondary malignancies after radiotherapy. This study evaluated the incidence of secondary malignancies after neoadjuvant chemotherapy. Between April 1972 and December 1990, 518 osteosarcoma and 299 Ewing's sarcoma patients entered neoadjuvant chemotherapy protocols. Follow-up records of all patients were analyzed and malignant tumors were reported. Nine patients developed another malignancy, including 5 leukemias, 1 astrocytoma, 1 liposarcoma, 1 parotid, and 1 breast carcinoma. Four leukemias were found in patients treated for osteosarcoma with chemotherapy, but not radiotherapy. Only one leukemia developed after Ewing's sarcoma treated with chemotherapy and radiotherapy. The incidence of leukemias is high, while the other tumors can be explained as unrelated cases. Incidence densities for leukemia were calculated for both groups of patients. Treated osteosarcoma patients seem to have a predisposition to develop leukemias, but whether this is chemotherapy induced needs to be investigated.

Preventive strategies require identification of cancer-susceptible individuals resulting from combinations of carcinogen exposure, cancer-predisposing genes, and lack of protective factors. To this aim, related to tobacco smoking and chewing (betel quid), we measured PAH-DNA adducts as exposure and susceptibility markers together with genetic polymorphism in drug-metabolizing enzymes related to CYP1A1, GSTM1, and GSTT1 genes in case-control studies. (+)-anti-Benzo(a)pyrene diol-epoxide (BPDE)-DNA adduct levels were quantitated in white blood cells (WBCs) and lung tissue DNA. CYP1A1 polymorphism and GSTM1 or GSTT1 gene deletion was analyzed in genomic DNA from lung parenchyma, WBCs, or oral biopsies (leukoplakia patients from India) and from oral exfoliated cells (healthy controls). Results from lung cancer patients and PAH-exposed coke oven workers correlated CYP1A1-GSTM1 genotype combinations with BPDE-DNA adduct levels. Smokers with homozygous CYP1A1 variant and GSTM1 null had the highest adduct levels and were, as shown in Japanese smokers, most susceptible to lung cancer. In oral premalignant leukoplakia cases associated with betel quid/tobacco chewing, the prevalence of the GSTM1 null and GSTT1 null genotypes was significantly higher, as compared to healthy controls. The combined GST null genotypes prevailed in 60% of the cases with none detected in controls. Based on this short review we conclude that (i) BPDE-DNA adduct levels resulting from "at risk" genotype combinations may serve as markers to identify most susceptible individuals; (ii) in Indian betel quid/tobacco chewers, the null genotypes of GSTM1 and GSTT1 greatly increased the risk for developing oral leukoplakia.

Expression of p53, K-ras, and proliferating cell nuclear antigen (PCNA) and mutations of p53 and K-ras genes in lung lesions of Han/Wistar rats were investigated by immunohistochemistry and direct DNA sequencing following a long-term exposure of animals to neutron-activated UO2 particles. The p53 protein was overexpressed in all five malignant tumors, in 62% of benign tumors, and in 42% of hyperplastic lesions examined. K-ras protein and PCNA levels were only slightly elevated in all types of lung lesions. In three malignant tumors a C-->T transition was detected in codon 288 (human 290) of the p53 gene, but this mutation was not present in seven other tumors analyzed. No mutations were detected in codons 12/13 and 61 of the K-ras gene in any of the five tumors analyzed. Our findings suggest that K-ras overexpression is a rare alteration, whereas p53 protein overexpression (sometimes associated with mutated p53 gene), as assessed with the CM5 antibody, is a relatively common phenomenon in hot particle-induced preneoplastic and neoplastic rat lung lesions.

Helicobacter pylori infection is associated with gastric adenocarcinoma. However, the mechanisms of this interaction are still unclear. This study was conducted to explore the effects of H. pylori infection on early and late stage gastric carcinogenesis. This study included 134 patients with adenocarcinoma of the stomach (ACS), 67 patients with chronic atrophic gastritis (CAG), and 65 normal controls recruited at Memorial Sloan-Kettering Cancer Center (MSKCC) from November 1, 1992 to November 1, 1994. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. H. pylori infection was diagnosed by pathological evaluation. Risk factors were analyzed using logistic regression. The odds ratio (OR) associated with H. pylori infection was 10.4 [95% confidence interval (CI): 2.6-41.6] for CAG and 11.2 (95% CI: 2.5-50.3) for gastric cancer in comparison with normal controls, with adjustment for pack-years of smoking, alcohol drinking, body mass index, total caloric intake, dietary fat and fiber intake, and Barrett's esophagus. But H. pylori infection was not associated with risk of stomach cancer when patients with stomach cancer were compared with patients with CAG (OR = 0.6, 95% CI: 0.3-1.3) after controlling for potential confounding variables. This association was persistent when only patients with both gastric cancer and chronic gastritis were considered as cases and patients with CAG were considered as controls (OR = 0.7, 95% CI: 0.3-2.0) in the multivariate analysis. Our results suggest that H. pylori infection may be involved in the early stage of development of CAG, but not in the development of stomach cancer from CAG, and indicate that strategies for prevention of stomach cancer should target the early stage to eliminate H. pylori infection in high-risk populations.

Meta-analyses of the relationship between dietary fat and breast cancer risk using different methodologies have reported conflicting results. This investigation compares methodologic aspects of meta-analyses of patient data (MAP) with meta-analyses of data from the literature (MAL), and computes relative risk (RR) estimates from a random effects model using 28 published studies of dietary fat and breast cancer. MAP and MAL results compare closely when homogeneity is verified. When statistical homogeneity is rejected, a random effects model adjusting for study design and location is appropriate. The highest RR was found for case-control studies of European women (RR: 1.46), followed by North American case-control studies (RR: 1.25), case-control studies of women on other continents (RR: 1.23), cohort studies in Europe (RR: 1.20), and cohort studies in North America (RR: 1.02). The overall risk estimate in a MAL with heterogeneous studies should be interpreted only in a conditional model.

This cohort of 252 subjects in the Roger Williams Hospital Polyp Registry who had adenomatous polyps removed in 1990, was followed for 6 years. Thirty subjects died during that period. Follow-up rate for the 222 living patients (88.1% of total) was 85%. New adenomatous polyps were found in 59% of the endoscoped subjects. Risk factors for new polyps included family history of colorectal carcinoma (p = 0.00079), right-sided location (p = 0.0108), and (probably) prior adenomatous polyps (p = 0.0595). In addition, three colorectal carcinomas, two of which were Dukes stage A, were found 1, 1, and 6 years after index polypectomy. If, as is common practice, the two first-year cancers are excluded, the observed incidence of metachronous colorectal cancer was 0.8/1000 patient years, which is substantially less than the expected incidence of such carcinomas in reference populations. Compared to the 1984 and 1987 cohorts in the polyp registry, colonoscopy was used more frequently and sigmoidoscopy less so for surveillance. Within the sigmoidoscopy group, the flexible instrument continued to rise in popularity as compared with rigid sigmoidoscopy. In addition to helping reduce the incidence of metachronous colorectal carcinomas, the polyp registry also serves the educational function of sensitizing physicians and their patients to the need to detect and treat these premalignant lesions. Enrollees in the registry also provide a source for studies designed to evaluate possible inhibitory effects of dietary, chemopreventive, and other agents on colorectal neoplasias.

The intracellular fluorescein fluorescence polarization (IFFP) test indicates that peripheral blood lymphocytes (PBL) of cancer patients display stimulatory sensitivity to a short incubation with specific tumor protein extracts. In this work, a human lymphocyte activation melanoma antigen (LAMA) was purified from supernatant of a human melanoma cell line (L1M1), which could specifically stimulate lymphocytes of melanoma patients. The results showed a significant stimulation of lymphocytes from healthy donors after incubation with phytohaemagglutinin (PHA), while no stimulation was observed after incubation with LAMA. On the other hand, lymphocytes from melanoma patients showed a significant stimulation with LAMA, while generally showing minor or no stimulation with PHA. Melanoma specificity of LAMA was demonstrated by no response in lymphocytes from patients of lung, colon, or breast cancer. The purified fraction is therefore considered to be a shared tissue-specific antigen which may be useful in immunodiagnosis and immunotherapy of melanoma.