Cancer In High-risk Groups Research Articles

Serum Proteomic Profiling of Lung Cancer in High-Risk Groups and Determination of Clinical Outcomes

Lung cancer remains the leading cause of cancer-related mortality worldwide. Currently known serum markers do not efficiently diagnose lung cancer at early stage. In the present study, we developed a serum proteomic fingerprinting approach coupled with a three-step classification method to address two important clinical questions: (i) to determine whether or not proteomic profiling differs between lung cancer and benign lung diseases in a population of smokers and (ii) to assess the prognostic impact of this profiling in lung cancer. Proteomic spectra were obtained from 170 pathologically confirmed lung cancer or smoking patients with benign chronic lung disease serum samples. Among the 228 protein peaks differentially expressed in the whole population, 88 differed significantly between lung cancer patients and benign lung disease, with area under the curve diagnostic values ranging from 0.63 to 0.84. Multiprotein classifiers based on differentially expressed peaks allowed the classification of lung cancer and benign disease with an area under the curve ranging from 0.991 to 0.994. Using a cross-validation methodology, diagnostic accuracy was 93.1% (sensitivity 94.3%, specificity 85.9%), and more than 90% of the stage I/II lung cancers were correctly classified. Finally, in the prognosis part of the study, a 4628 Da protein was found to be significantly and independently associated with prognosis in advanced stage non-small cell lung cancer patients (p = 0.0005). The potential markers that we identified through proteomic fingerprinting could accurately classify lung cancers in a high-risk population and predict survival in a non-small cell lung cancer population.

Cost-utility analysis of screening high-risk groups for anal cancer

Cost-utility analysis of screening for anal cancer in high-risk groups from a UK perspective. Criteria for the assessment of screening programmes were combined in a Markov model representing the natural history of anal cancer and HIV infection in the UK population of men who have sex with men (MSM). Alternative screening programmes were overlaid on the natural history model to evaluate their impact. The model was populated using data derived from a systematic review of the literature, and calibrated probabilistically to represent joint uncertainty in the input parameters. Reference case results showed screening is unlikely to be cost-effective. Sensitivity analyses identified two important parameters: regression from low-grade anal intra-epithelial neoplasia (AIN) and utility effects. Increased AIN regression rates resulted in a minimum incremental cost per QALY gained of 39,405 pounds, whereas a best case scenario reduced the ratio to 20,996 pounds. There are major areas of uncertainty. New analyses of existing primary data, undertaken specifically to inform regression rates may usefully update key parameters at little additional cost. If these analyses increase the likelihood that screening is cost-effective, further studies of the utility effects of treatment for high-grade AIN, and potential screening attendance rates may be justified.

Breast Cancer Onset in Twins and Women With Bilateral Disease

Little is known of the onset of breast cancer in high-risk populations. We investigated the risk of breast cancer in twin sisters and in the contralateral breast taking family history into consideration. We analyzed a Scandinavian population-based cohort of 2,499 female twin pairs, in which at least one had a diagnosis of breast cancer and estimated the risk of breast cancer in the sister. Using a total of 11 million individuals in Sweden with complete family links, we identified 93,448 women with breast cancer and estimated the risk of a bilateral breast cancer. The incidence of breast cancer in twin sisters of breast cancer patients was 0.64% per year and 0.42% per year in mono- and dizygotic twin sisters, respectively. In comparison, the risk of familial (affected first-degree relative) and nonfamilial bilateral breast cancer was 1.03% per year and 0.68% per year, respectively. Contrary to the risk of unilateral disease, the risk of cancer in the nonaffected twin and the opposite breast was not affected by age or time since first event. The relative risk of familial bilateral cancer was 52% higher (incidence rate ratio [IRR] = 1.52; 95% CI, 1.42 to 1.64) and the relative risk in the dizygotic twin sister was 25% lower (IRR = 0.75; 95% CI, 0.61 to 0.91) compared with the risk of nonfamilial bilateral cancer. The elevated risk of breast cancer in high-risk groups is little affected by age and time since diagnosis. Our findings suggest that susceptible groups of women might have already aggregated genetic prerequisites for breast cancer.

Examination of a gastric cancer high-risk group in a mass screening of the stomach using interleukin 1-beta polymorphism an alysis and the serum pepsinogen test

Examination of a gastric cancer high-risk group in a mass screening of the stomach using interleukin 1-beta polymorphism an alysis and the serum pepsinogen test

Incidence and Detection of Contralateral Breast Cancer

In this study we estimated the efficacy of contralateral breast biopsy as a subsidiary method of early detection of bilateral breast cancer. We performed blind biopsies in the upper outer quadrant of the opposite breast in 195 patients undergoing surgical treatment for primary breast cancer. The histologic examination of the biopsy specimens showed 12 malignant lesions, which accounts for an incidence of 6.1%. In detail, we had two infiltrating ductal cancers, two infiltrating lobular cancers, three ductal in situ cancers, and five lobular in situ cancers. The overall incidence of invasive disease was 2.05%. We concluded that contralateral breast biopsy should be reconsidered as a method for enhancing early detection of contralateral breast cancer in high-risk groups, especially when it meets the emotional needs of patients. Permission given, it is included in the main surgical treatment of patients, avoiding the cost and complications of anesthesia, and it is cosmetically acceptable, without being an emotional burden for the woman.

Screening for Lung Cancer in High-Risk Groups: Current Status of Low-Dose Spiral CT Scanning and Sputum Markers

Lung cancer is the number one cause of death from cancer in the United States. Currently, there is no official recommendation to screen for lung cancer even in high-risk populations. Accordingly, we wait for patients to present with symptoms. Only 15-20% of patients are stage I lung cancer at diagnosis. Past screening trials with chest roentgenogram and sputum cytology did not show a reduction of lung cancer mortality in the screened population. Since the completion of those trials in the early 1980s we have learned that the chest X ray is not sensitive at detecting lesions <2 cm in size, and patients with chronic obstructive pulmonary disease (COPD) have a 4- to 6-fold increased risk of lung cancer independent of their smoking history. Recent trials with spiral computed tomography (CT) scan screening have detected 80-85% of lung cancers while they are stage I. The problems related to spiral CT screening are the cost and the frequent detection of benign lesions. Algorithms are being developed to try and prevent unnecessary biopsies and/or surgery. Sputum cytology is currently the only clinically approved sputum test for detecting lung cancer. However, in patients with moderate dysplasia of cytology, the LIFE autofluorescence bronchoscopy system may yield an increased sensitivity of detecting precancerous or cancerous lesions. More studies are needed before the LIFE system can be adopted as a standard clinical tool. Currently, investigators are evaluating the sputum for early lung cancer detection markers. The marker that is the most developed is the monoclonal antibody to the heterogeneous nuclear ribonucleoprotein A2/B1 on the sputum epithelial cell surface. Encouraging preliminary results have been reported and trials are ongoing. The future looks bright for the field of lung cancer screening.

Plasma Insulin-Like Growth Factor-I and Serum IGF-Binding Protein 3 Can Be Associated with the Progression of Breast Cancer, and Predict the Risk of Recurrence and the Probability of Survival in African-American and Hispanic Women

In vitro studies have shown that insulin-like growth factor (IGF) is a mitogen for breast cancer cells. However, the associations of plasma IGF-I with tumor histopathology in high-risk groups need further investigation. We hypothesize that plasma IGF-I and serum IGFBP3 concentrations in breast cancer patients may provide useful information on the progression of their disease, and determine the probability of recurrence and survival. We have carried out a retrospective study on 130 minority breast cancer patients. Plasma IGF-I and serum IGFBP3 were correlated with tumor histopathology, menopausal status, treatment modality, recurrence rates, and probability of survival. Plasma IGF-I and serum IGFBP3 were measured by radioimmunoassay. Our studies show that breast cancer patients have elevated plasma IGF-I and serum IGFBP3 levels. In addition we observed the following: IGF-I did not correlate with age and nodal stage. IGF-I and IGFBP3 increased with tumor size (T4). IGF-I did not correlate with estrogen receptor status, but did increase in progesterone-receptor-positive patients. IGF-I levels were higher in premenopausal patients and in women with cancer recurrence. Tamoxifen reduced IGF-I levels significantly and reduced the risk of recurrence. The survival probability was greater in patients with plasma IGF-I levels <120 ng/ml. In conclusion, lowering of plasma IGF-I may offer the following benefits: (a) reduce the risk of developing breast cancer in high-risk groups; (b) slow the progression of breast cancer in patients at early stages of cancer; (c) lower the risk of recurrence, and (d) increase the probability of survival.

Intestinal absorption of epoxy-β-carotenes by humans

An increased intake of fruits and vegetables has been shown to be associated with reduced risk of cancer. In epidemiological studies, supplements of β-carotene, which is abundant in fruits and vegetables, were not found to be beneficial in reducing the incidence of lung cancer in high-risk groups. Epoxycarotenoids are abundant in nature. 5,6-Epoxy-β-carotene was much more active than β-carotene in the induction of differentiation of NB4 cells [Duitsman, Becker, Barua and Olson (1996) FASEB J. 10, A732]. Epoxycarotenes may, therefore, have protective effects against cancer. In order to do this, however, epoxycarotenoids must be absorbed by the human body. There is no evidence that epoxycarotenoids, despite their abundance in dietary fruits and vegetables, are absorbed by humans. In this paper, it is demonstrated that orally administered dietary or synthetic epoxy-β-carotenes are absorbed by humans, as indicated by their appearance in the circulating blood.

Intestinal absorption of epoxy-β-carotenes by humans

An increased intake of fruits and vegetables has been shown to be associated with reduced risk of cancer. In epidemiological studies, supplements of beta-carotene, which is abundant in fruits and vegetables, were not found to be beneficial in reducing the incidence of lung cancer in high-risk groups. Epoxycarotenoids are abundant in nature. 5,6-Epoxy-beta-carotene was much more active than beta-carotene in the induction of differentiation of NB4 cells [Duitsman, Becker, Barua and Olson (1996) FASEB J. 10, A732]. Epoxycarotenes may, therefore, have protective effects against cancer. In order to do this, however, epoxycarotenoids must be absorbed by the human body. There is no evidence that epoxycarotenoids, despite their abundance in dietary fruits and vegetables, are absorbed by humans. In this paper, it is demonstrated that orally administered dietary or synthetic epoxy-beta-carotenes are absorbed by humans, as indicated by their appearance in the circulating blood.

Effects of antioxidants on vascular health

Substantial in vitro and animal model evidence implicates the free radical-mediated oxidation of low density lipoprotein and its subsequent preferential uptake by macrophages in the arterial intima as an important factor in the development of vascular disease. In addition, antioxidants which prevent the oxidation of LDL in vitro also reduce the severity of vascular disease in animal models. Although some epidemiological studies also suggest that inadequate antioxidant status is related to the development of vascular disease, particularly cardiovascular disease, results from intervention trials have been contradictory. Whereas vitamin E may have a role in reducing the incidence of vascular disease, evidence is less strong for vitamin C, flavonoids and beta-carotene. Additionally, supplementation with some antioxidants such as beta-carotene may increase the incidence of cancer in high risk groups. Although increasing antioxidant intake is generally beneficial for health, this should perhaps be achieved by an increased dietary intake of antioxidant-rich foods rather than by use of supplements.

Does Beta‐Carotene Supplementation Reduce (or Increase) Cancer Risk?

Epidemiologic studies have been very consistent in showing that consumption of dietary fruits and vegetables is inversely related to risk of certain cancers, especially lung cancer. It has been suggested that carotenoids, particularly β‐carotene, are the chemopreventive agents. Four long‐term, large, randomized intervention trials have been conducted to test the effectiveness of β‐carotene supplementation on cancer risk. The Alpha‐Tocopherol, β‐Carotene Cancer Prevention (ATBC) Study tested daily supplementation with 20 mg β‐carotene and 50 mg α‐tocopherol in smokers. The β‐Carotene and Retinol Efficacy Trial (CARET) tested daily supplementation with 30 mg β‐carotene and 25,000 IU of retinyl palmitate in adults at high risk for lung cancer (smokers, asbestos‐exposed). The Physicians’ Health Study (PHS) tested supplementation with 50 mg β‐carotene on alternate days in adults, 11% of whom were smokers. The Linxian (Chinese) Study tested daily supplementation with 15 mg β‐carotene, 50 μg selenium, and 30 mg α‐tocopherol in vitamin‐ and mineral‐deficient adults. The ATBC and CARET studies reported that β‐carotene increased the incidence of lung cancer in high risk groups. The PHS showed no effect of β‐carotene supplementation on cancer incidence. The Chinese study reported a lower mortality of total cancers. These results suggest that supplementation with β‐carotene for the prevention of cancer may pose a risk in smokers and asbestos workers and is of little benefit in preventing cancer in well‐nourished populations. Health benefits are more likely from increasing consumption of fruits and vegetables, including those rich in carotenoids. ▪ Key Words: carotenoids, beta‐carotene, cancer

Familial risk of lung cancer among nonsmokers and their relatives.

The role of family history of lung cancer in predicting lung cancer risk among nonsmokers and their relatives was evaluated in a population-based family study conducted in metropolitan Detroit. Lung cancer risk factor data were collected through telephone interviews with 257 nonsmoking lung cancer cases 40-84 years of age diagnosed between 1984 and 1987, their 2,252 relatives, 277 nonsmoking controls, and their 2,408 relatives. Lung cancer in a first-degree relative was associated with a 7.2-fold (95% confidence interval 1.3-39.7) increased risk of lung cancer among nonsmokers in the 40- to 59-year-old age group. This significant increased risk remained after adjustment for the smoking, occupational, and medical history of each family member (relative risk = 6.1, 95% confidence interval 1.1-33.4). Offspring of nonsmoking cases comprised another lung cancer high risk group (relative risk = 7.2, 95% confidence interval 0.5-103). A positive family history did not increase lung cancer risk among nonsmokers 60-84 years of age or their relatives. These findings suggest that susceptibility to lung cancer in families of nonsmoking cases may be evident only in a subset of relatives of early-onset nonsmoking cases.

Medium-term protocols for in vivo evaluation of chemical modifiers of carcinogenesis

Cancer development is a long-term multistep process which allows interventional measure before the clinical disease emerges. The detection of natural substances which can block the process of carcinogenesis is as important as the identification of anti-tumoral drugs since they might be used in chemoprevention of cancer in high-risk groups. In vivo rodent models of chemical carcinogenesis have been used to study plant-derived inhibitors of carcinogenesis such as indoles, coumarins, isothiocyanates, flavones, phenols and allyl-sulfides. Since the standard in vivo rodent bioassay is prolonged and expensive, shorter reliable protocols are needed. Two in vivo medium-term protocols for evaluation of modifiers of carcinogenesis are presented, one related to liver and the other to bladder cancer. Both protocols use rats, last 8 and 36 weeks and are based on the two-step concept of carcinogenesis: initiation and promotion. The protocols use respectively the development of altered foci of hepatocytes expressing immunohistochemically the placental form of glutathione S-transferase and the appearance of pre-neoplastic urothelium and papillomas as the "end-points". The use of these protocols for detection of plant-derived inhibitors of carcinogenesis appear warranted.

Molecular and Cellular Biological Approaches and Techniques in the Detection of Bladder Cancer and Enhanced Risk for Bladder Cancer in High-Risk Groups

Recent advances in molecular cell biology, immunology, and toxicology enhance detection of actual and incipient disease and the definition of risk. Tumor-associated antigens may greatly improve detection of low-grade tumor cells. Several new strategies depend upon detecting molecular lesions of the genes controlling cell growth (oncogenes) at either the gene or protein levels. Highly sensitive techniques detecting DNA adducts are refining the ability to detect specific DNA damage shortly after exposure. The recognition of controls that actively stop proliferation (tumor suppressor genes), regulate differentiation or of relationships between metabolism and carcinogenesis may lead to new ways to identify persons genetically at increased risk from carcinogenic exposure. Current technologies, those on the near horizon, and long-term research needs are analyzed critically in terms of screening objectives.

Screening for Bladder Cancer in High-Risk Groups: Delineation of the Problem

Since 1895, various exogenous chemicals and occupations have been identified as risk factors for bladder cancer. The aromatic amines are among the most notable chemicals. To date, numerous groups of workers and, in some cases, community residents, who are at increased risk of bladder cancer have come to the attention of health officials and have sought guidance concerning screening for bladder cancer. Most of these persons are asymptomatic, but they may not have attained the average length of preclinical latency for aromatic amine-induced cancer. Although the principal public health strategy for combatting occupational exposure to carcinogens is primary prevention, screening is another strategy that can be used for those already exposed to known or suspected carcinogens. Screening also can be used to assess whether or not environmental controls are needed or need to be improved. For more than a decade the question of screening has been problematic with regard to occupational groups where known exposures have been documented. The question facing government, labor, industry, and academia is what to recommend with regard to screening high-risk groups.

Detection of Exfoliated Bladder Cancer Cells by Monoclonal Antibodies to Tumor- Associated Cell Surface Antigens

Monoclonal antibodies (Mabs) to human tumor antigens have potential for tumor detection and treatment. For bladder carcinoma, the detection of exfoliated tumor cells in urinary specimens may be accomplished with Mabs reacting to tumor cell-surface components. This method may be useful for screening and monitoring carcinogen-exposed workers. A Mab generated by our laboratory, 3G2-C6, reacts with high affinity to a cell-surface component expressed by bladder tumor cells. The potential utility of this Mab in detecting exfoliated tumor cells was evaluated in bladder wash specimens. The Mab method detected positive cells in 87% (56/64) of specimens from patients with bladder cancer, including a great majority with grade 1 tumor and carcinoma in situ, superior to the routine cytology done on the same specimens. Cells in specimens from patients with urinary calculi, chronic cystitis, and history of bladder cancer also reacted with the Mab, suggesting that other stimuli can induce antigen expression. The Mab method can also be performed on urine samples, thus allowing evaluation of the ability of the Mab to identify premalignant, malignant, and other abnormal exfoliated cells in urine. The Mab method represents a unique opportunity to develop noninvasive detection of bladder cancer and to monitor and screen bladder cancer high-risk groups.

Screening for lung cancer high-risk groups.

Screening for lung cancer high-risk groups.