Showing papers in "European Journal of Cancer Prevention in 1996"

The role of iron in cancer.

Abstract: Numerous laboratory and clinical investigations over the past few decades have observed that one of the dangers of iron is its ability to favour neoplastic cell growth. The metal is carcinogenic due to its catalytic effect on the formation of hydroxyl radicals, suppression of the activity of host defence cells and promotion of cancer cell multiplication. In both animals and humans, primary neoplasms develop at body sites of excessive iron deposits. The invaded host attempts to withhold iron from the cancer cells via sequestration of the metal in newly formed ferritin. The host also endeavours to withdraw the metal from cancer cells via macrophage synthesis of nitric oxide. Quantitative evaluation of body iron and of iron-withholding proteins has prognostic value in cancer patients. Procedures associated with lowering host iron intake and inducing host cell iron efflux can assist in prevention and management of neoplastic diseases. Pharmaceutical methods for depriving neoplastic cells of iron are being developed in experimental and clinical protocols.

Symmetry of projection in the quantitative analysis of mammographic images

Abstract: Mammographic parcnchymal patterns are among the strongest indicators of the risk of developing breast cancer. Risk evaluation through breast patterns may have an important role in studies of the aetiology of breast cancer and for monitoring changes in the breast in evaluating potential risk-modifyin

Dietary factors and risk of colon cancer: a prospective study of 50,535 young Norwegian men and women.

Abstract: The relationship of meat, fish, fat, fibre or calcium consumption to the risk of colon cancer was examined in a prospective study conducted by the Norwegian National Health Screening Service. Between 1977 and 1983, 50,535 Norwegian men and women aged 20-54 attended the health screening and completed a semi-quantitative questionnaire about food frequency. During a mean follow-up of 11.4 years, 143 cases of colon cancer were identified for analyses through a link with the Norwegian Cancer Registry. The relative risk of colon cancer was 3.5 (95% CI, 1.02-11.9) in women who consumed sausages as their main meal five or more times a month, compared with the risk in those who reported a consumption frequency of less than once a month. There was an increase in the relative risk with increasing frequency of consumption (P for linear trends = 0.03). Among men, the association was not statistically significant, but the trend was in the same direction as that of the women. The frequency of consuming meat meals in general, including meat stews, roasted meat, meat balls, fish or milk, was not associated with a risk of colon cancer. No trends in relative risks of colon cancer were found to be associated with intake of total energy intake or with energy-adjusted intake of total fat, saturated fat, monounsaturated fat, dietary fibre or calcium. In conclusions, this prospective study provided no evidence of association between intake of meat, fish, fat, energy, fibre or calcium and risk of colon cancer, although an increased risk with frequent consumption of sausages was suggested.

Barrett's esophagus: ordering the events that lead to cancer.

Abstract: A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of two antioxidant treatments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.

Tea and cancer: a review of the epidemiological evidence.

Abstract: Numerous recent reports of inhibition of carcinogenesis in experimental animals by tea or tea compounds raise the possibility that tea drinking may lower cancer risk in humans. Thus, studies around the world were reviewed to evaluate whether there is a consensus of epidemiologic evidence on the relation of tea drinking to cancer overall or to specific cancers. Ecological data suggest at most a modest benefit, since there is considerable international variation in tea consumption but generally small differences in cancer rates. More relevant case-control and cohort studies show mixed results. Detailed data from these studies on cancer risks according to amount and duration of tea intake are quite limited, and consistent dose-related patterns. have yet to emerge. Nevertheless, several investigations point to the possibility of lowered risks of digestive tract cancers among tea drinkers, especially those consuming green tea. Further research, particularly in population with wide ranges of tea consumption, is needed before definitive conclusions on tea's impact upon cancer risk can be reached.

Cigarette smoking and the risk of breast cancer.

Abstract: The relation between cigarette smoking and breast cancer risk was investigated in a multicentric case-control study conducted in Italy on 2,569 women with incident, histologically confirmed breast cancer and 2,588 control women admitted to hospital for acute, non-neoplastic, non-hormonal, non-gynaecological or smoking-related conditions. Compared with women who had never smoked, current smokers had a multivariate odds ratio (OR) of 0.84 [95% confidence interval (CI) 0.7-1.0] and former smokers an OR of 1.14 (5% CI 0.9-1.4), while the OR for ever vs never smokers was 0.93 (95% CI 0.8-1.1). The ORs were 1.02 for or = 25 cigarettes per day. No consistent pattern of risk was observed according to duration of smoking, age at starting and time since starting smoking. Compared with never smokers, former smokers had ORs of 1.45 for or = 16 years. No heterogeneity emerged across strata of selected covariates. Thus, this study, one of the largest conducted in Europe to date, does not support the presence of any association of practical importance between cigarette smoking and breast cancer risk.

Mammograms may convey more than breast cancer risk: breast arterial calcification and arterio-sclerotic related diseases in women of the DOM cohort.

Abstract: In a cohort of 12,239 women aged 50-69, who participated in a population-based breast cancer screening project (DOM-project) in Utrecht, The Netherlands, as well as being coded for micro-calcifications indicative of breast cancer, the mammograms were also coded for arterial calcifications. This allowed for a secondary analysis of associations between breast arterial calcification (BAC) and the occurrence of arteriosclerosis-associated morbidity (ie diabetes, hypertension, albuminuria, stroke, thrombosis and myocardial infarction). Arterial calcifications were seen on screening mammograms in 9.1% of the women. Significant relations were found between BAC and albuminuria [Relative risk (RR) 2.7; 95% CI 1.0-7.0], BAC and hypertension (RR 1.1; 95% CI 1.0-1.3), transient ischaemic attack (TIA)/stroke (RR 1.4; 95% CI 1.1-1.8), thrombosis (RR 1.5; 95% CI 1.0-2.2) and myocardial infarction (RR 1.8; 95% CI 1.1-2.9). In addition BAC were associated with diabetes in the oldest age-group (RR 1.7; 95% CI 1.2-2.4). All relations were adjusted for age, smoking, parity and Quetelet index. The results of the present study show that BAC as detected on breast cancer screening mammograms are associated with disorders related to increased or accelerated arterio-sclerosis. Where increased parity is associated with a decrease in breast cancer risk, parity increases the occurrence of BAC. The present study suggests that breast-cancer screening mammograms may allow for the early detection of enhanced cardiovascular disease risk among otherwise healthy women.

Butyrate, aspirin and colorectal cancer.

Abstract: In vitro, for animal cells generally, butyrate at millimolar concentrations is an inhibitor of growth. In vivo, however, colonocytes are able to grow in the environment of about 20 mM butyrate produced by bacterial fermentation on the luminal side of the colonic epithelium. An in vivo increase of the butyrate supply results in growth stimulation of cells in the colonic crypts. This discrepancy, namely, that in cell cultures butyrate is an inhibitor of growth, whereas in vivo it has a trophic effect, is the so called in vivo paradox of butyrate. In the present review it is pointed out that butyrate is an inhibitor of histone deacetylases and there is sufficient evidence for hyperacetylation being the mechanism of the in vitro growth-inhibiting effect of butyrate. As within animal cells hyperacetylation has to occur at a certain butyrate concentration (1-10 mM), it is postulated that the in vivo lack of inhibition and 'paradoxical' stimulation of growth is a result of a low intracellular steady state concentration of butyrate in the lower layers of the crypt in spite of the much higher butyrate concentration on the luminal side. As butyrate is the preferential source of energy for colonocytes, the in vivo trophic effect is not paradoxical, when in spite of an increase of the butyrate concentration in stool, the intracellular butyrate concentration of intestinal epithelial cells still remains below the inhibiting level. For mature non-dividing colonocytes which are programmed for apoptosis, there is no difference between the observations made in vitro or in vivo. Furthermore, recent developments are discussed which suggest that cyclo-oxygenase-2 may play an essential role in colonic carcinogenesis. Cyclo-oxygenase-2 is found to be expressed in most colorectal carcinomas, but not in normal non-transformed intestinal epithelial cells (DeWitt and Smith, 1995). Cyclo-oxygenase-2 overexpression makes intestinal epithelial cells resistant to butyrate-induced apoptosis (Tsujii and DuBois, 1995). This escape from butyrate-induced apoptosis appears to be an essential prerequisite for the development of colorectal cancer and suggests a functional role of butyrate in growth, differentiation and programmed cell death of colonic epithelial cells.

Breast size and mammographic pattern in relation to breast cancer risk.

Abstract: The relation of Wolfe's parenchymal patterns and radiographically-assessed breast size with breast cancer risk was evaluated in a population-based nested case-control study in Uppsala, Sweden. All women who attended a mammographic screening programme in Uppsala county starting in 1988 have been followed for the occurrence of breast cancer through 1993. The analysis was based on 295 cases and 589 age-matched controls, whose mammograms were blindly evaluated for parenchymal pattern and breast size. Women with P2 or DY pattern had a significantly elevated risk of breast cancer compared with women with N1 or P1 (OR = 2.09; 95% CI = 1.52-2.86). There was an inverse association of breast size with breast cancer risk, which disappeared after adjusting for parenchymal pattern, because breasts of smaller size tended to have high-risk parenchymal patterns. It is concluded that in Swedish women, and perhaps in Caucasian women in general, small breast size is associated with increasing breast risk through its association with high-risk parenchymal pattern. This is in contrast to the fact that Asian women, who in general have breasts of smaller size, have low prevalence of high-risk parenchymal pattern as well as low rates of breast cancer.

Hereditary and environmental risk factors; clinical and laboratory risk matters for head and neck, especially oral, cancer and precancer.

Abstract: The continuing high incidence and mortality of squamous cell carcinoma of the upper aerodigestive tract in South Asia, parts of France and central Europe, together with a rising incidence and mortality from a lower base elsewhere in the Western world, stimulates continuing research on risk factors and risk markers. Tobaccos (smoked and smokeless), heavy alcohol consumption, and areca nut remain the dominant risk factors, with confirmation of the protective effects of diets rich in antioxidants. There is emerging evidence of a small, but real, risk associated with occupational and other air pollution, and with family, part of which may be hereditary. Markers in peripheral blood and saliva are underexploited. Clinical staging and histological grading methods continue to be refined, with improved prognostic value, much aided by newer and simpler methods for estimating cell proliferation and apoptosis. Data on the significance of viral genes are still inadequate, but there is good progress describing the epidemiology of chromosomal abnormalities and abberations of a growing list of oncogenes and tumour suppressor genes. Unfortunately, as yet, these have only limited longitudinal or prognostic data.

Extra low frequency electric and magnetic fields in the bedplace of children diagnosed with leukaemia: a case-control study.

Abstract: This retrospective case-control study of 56 cases and 56 controls measured extra low frequency (ELF) electric and magnetic fields between 2000 h and 0800 h in the bedplaces of children with leukaemia. Mean ELF electric field (E-field) levels found in case homes of 13.9 Vm -1 (SD: 13.6) were significantly higher (P < 0.01) compared with only 7.3 Vm -1 (SD: 12.9) in controls matched for age and sex. Moreover, applying conditional logistic regression, a dose-response relationship emerged between E-field exposure and incidence: above 20 Vm -1 the relative risk was 4.69 (95% CI: 1.17-27.78; P = 0.025), whereas at levels of 10-19 Vm -1 it was 2.40 (95% CI: 0.79-8.09) and at levels of 5-9 Vm -1 it was only 1.46 (95% CI: 0.47-5.10). By contrast, similar readings of the rms ELF magnetic field found no significant case-control differences: mean levels in cases' homes of 0.070 μT (SD: 0.070) compared with 0.057 μT (SD: 0.038) in controls. Although there were imperfections in the study design, it is concluded that the importance of the E-field may have been overlooked in epidemiological studies to date.

Hormonal events during female puberty in relation to breast cancer risk.

Abstract: The time from puberty to the first pregnancy is particularly important for breast cancer risk, with early menarche increasing the risk of breast cancer. The onset of puberty is elicited by an increase in gonadotropin secretion, that can be modified by metabolic factors. Girls going to have an early menarche, have an earlier and greater increase of follicle stimulating hormone and oestradiol. After menarche, girls having had menarche before 12 years of age have a more rapid onset of ovulatory menstrual cycles, than girls having later menarche. Significantly higher serum oestradiol and lower sex hormone binding globulin concentrations are seen in women having had early menarche, and the differences still remain at 20-30 years of age. Thus, early menarche is associated with increased oestrogen and progesterone secretion, that might induce a higher degree of breast epithelial proliferation. Further research is required concerning the possible role of physical exercise and nutrition in modifying breast cancer risk.

A post-Chernobyl rise in thyroid cancer in Connecticut, USA.

Abstract: Recent analyses of children in Belarus and the Ukraine are the first to document large numbers of excess thyroid cancer cases only 4 years after exposure to radiation. In Connecticut (USA), a thyroid cancer increase of a much smaller magnitude occurred in 1990-93, 4-7 years after the Chernobyl accident, for both children and adults. Similar changes also occurred in the states of Iowa and Utah, which like Connecticut were exposed to low levels of radionuclides from Chernobyl fallout during May and June of 1986. Historical data from Connecticut also reveal substantial increases in thyroid cancer incidence about 5 years after large releases of iodine-131 from distant US nuclear weapons plants, after the largest atmospheric US atomic weapons tests in Nevada, and after substantial releases of iodine-131 from the Millstone nuclear power plant in Connecticut. Further analysis of this apparent 5-year latency period will enhance understanding of ionizing radiation's effects on thyroid function and on human health in general.

Pattern of pS2 protein expression in premalignant and malignant lesions of gastric mucosa.

Abstract: The aim of this study was to evaluate the pattern of pS2 protein expression in premalignant and malignant lesions of gastric epithelium. We analysed, by immunohistochemistry, the pS2 expression in six samples of normal gastric mucosa, 18 cases of chronic atrophic gastritis with intestinal metaplasia (IM), 10 hyperplastic polyps, 11 adenomatous polyps and 50 gastric carcinomas, together with the respective samples of adjacent non-neoplastic mucosa. pS2 is expressed throughout foveolar and superficial epithelium of normal gastric mucosa and this pattern is retained in chronic atrophic gastritis out of IM lesions. pS2 expression is confined to goblet cells in complete IM and occurs both in goblet and columnar cells in incomplete IM. Hyperplastic polyps displayed significantly higher pS2 expression than adenomatous polyps. In gastric carcinomas, pS2 expression was observed in 66.0% of cases, being significantly higher in diffuse (88.9%) than intestinal type carcinomas (53.6%). A subset of carcinomas of the latter group displayed pS2 immunoreactivity in a high percentage of cells with a pattern similar to that of hyperplastic polyps. Our results demonstrate there are major changes in pS2 expression, which can be used as a marker of gastric-type differentiation during the process of gastric carcinogenesis, and support the existence of at least two pathways of malignant transformation of gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.

A high performance liquid chromatography system for quantification of hydroxyl radical formation by determination of dihydroxy benzoic acids.

Abstract: The hypoxanthine/xanthine oxidase enzyme system is known to produce the superoxide ion and hydrogen peroxide during the hydroxylation of hypoxanthine via xanthine to uric acid. When chelated iron is included in this system, superoxide reduces iron (III) to iron(II) and the iron(II)-chelate further reacts with hydrogen peroxide to form the highly reactive hydroxyl radical. Because of the limitations of colourimetric and spectrophotometric techniques by which, to date, the mechanisms of hydroxyl radical formation in the hypoxanthine/xanthine oxidase system have been monitored, a high performance liquid chromatography method utilizing the ion-pair reagent tetrabutylammonium hydroxide and salicylic acid as an aromatic probe for quantification of hydroxyl radical formation was set up. In the hypoxanthine/xanthine oxidase system the major products of hydroxyl radical attack on salicylic acid were 2,5-dihydroxy benzoic acid and 2,3-dihydroxy benzoic acid in the approximate ratio of 5:1. That the hydroxyl radical is involved in the hydroxylation of salicylic acid in this system was demonstrated by the potency especially of dimethyl sulphoxide, butanol and ethanol as scavengers. Phytic acid, which is considered to be an important protective dietary constituent against colorectal cancer, inhibited hydroxylation of salicylic acid at a concentration one order of magnitude lower than the classical scavengers, but was only effective in the absence of EDTA. The method has been applied to the study of free radical generation in faeces, and preliminary results indicate that the faecal flora are able to produce reactive oxygen species in abundance.

Strengths and weaknesses of screening programmes for oral malignancies and potentially malignant lesions.

Abstract: Screening for oral cancer is in an early stage of development. No randomized controlled trials have been undertaken to determine the impact of screening on mortality or even on interim outcomes such as incidence or down-staging. Until such data are available, mass screening for oral cancer is not recommended as public health policy. Case finding studies to identify individuals at risk because of life-style, and to detect potentially malignant oral mucosal changes followed by appropriate intervention may, however, reduce the future incidence of oral cancer. Where manpower is available, opportunistic screening focused on high-risk subjects may be beneficial.

Case-control study of risk factors for cervical squamous cell neoplasia in Denmark. IV: role of smoking habits.

Abstract: The role of smoking and other risk factors for cervical neoplasia was investigated in a population-based case-control study of 586 women with histologically verified cervical squamous-cell carcinoma in situ (CIS), and 59 women with invasive squamous-cell cervical cancer from Copenhagen. Controls were randomly selected from the general female population using the computerized Danish Central Population Register. After adjustment for a variety of confounding variables, which were all significantly associated with CIS risk and included age, number of partners, proportion of sexually active life without barrier contraceptive use, years with intra-uterine devices, number of births, and age at first episode of genital warts (as a proxy measure for human papillomavirus exposure), current cigarette smoking was found to be significantly associated with CIS [adjusted relative risk (RR) = 2.4; 95% confidence interval (CI): 1.7-3.4]. Ex-smokers had a lower, but still significantly increased risk (RR = 1.6; 95% CI: 1.0-2.7). A dose-response relationship was present, especially for number of cigarettes smoked per day. In contrast, the crude estimates showed a weak association between invasive cervical cancer and smoking, which however disappeared after confounder control. The results of the present study support the hypothesis implicating smoking as a risk factor for CIS.

Expression of a peptide epitope of the colonic mucin MUC2 in precursor lesions to gastric carcinoma.

Abstract: Previous histochemical studies have shown that changes occur in the composition of mucins both in preneoplastic and neoplastic lesions of the gastric mucosa. Since monoclonal antibodies are now available which recognize the protein product of distinct mucin genes, they are likely to provide useful tools for evaluating these changes. Thus, a monoclonal antibody 996/1 raised against a peptide epitope of the colonic mucin MUC2 was examined for its potential as a prognostic indicator in gastric cancer. 996/1 works well on formalin-fixed paraffin sections and shows good staining of the colonic goblet cells in the region of the golgi, while there is no staining of normal control gastric mucosa. The epitope was detected in all cases of intestinal metaplasia (44 samples) and some but not all cases of dysplasia (26 samples) and gastric carcinoma (74 samples). There was no significant difference between the positivity of the tumours according to their classification, stage and lymph node status. These results unfortunately gave little indication that this antibody would be a useful prognostic tool in gastric cancer. However, the pattern of 996/1 staining provides useful information about the molecular changes in mucin expression that occur in gastric carcinogenesis.

Increased concentrations of octachlorodibenzo-p-dioxin in cases with breast cancer--results from a case-control study.

Abstract: Organochlorines are persistent and highly lipophilic environmental contaminants which bioaccumulate in the food chain. Some of these chemicals, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), have been suggested to be of significance in the aetiology of breast cancer. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an anti-oestrogen in animal studies and should thus lower the risk of breast cancer. The other isomers of polychlorinated dibenzo-p-dioxins (PCDDs) or the chemically related polychlorinated dibenzofurans (PCDFs) have not been tested regarding carcinogenesis of the breast. The purpose of this study was to investigate whether PCDDs or PCDFs influence the risk for breast cancer. Consecutive patients who underwent surgery for a breast disease between 1993 and 1995 were recruited for the study. Cases were 22 patients with infiltrative breast cancer and controls were 19 patients operated for a benign breast disease during the same time period. Approximately 10 g of breast tissue free from tumour was taken from the specimen and frozen until analysis. Fat was extracted, cleaned and analysed with a high-resolution gas chromatograph coupled to a high-resolution mass spectrometer. Median concentrations of octachlorinated dibenzo-p-dioxin (OCDD) were 598 (170-14,880) and 396 (103-1,847) pg/g lipid in the cases and in the controls, respectively. In a multivariate logistic regression analysis controlling for other risk factors for breast cancer increased odds ratio (OR) was obtained for OCDD: 401-1000 pg/g lipid yielded OR 3.8, 95% confidence interval (CI) 0.4-39, >1000 pg/g lipid gave OR 5.2, CI 0.4-72. When the lipid OCDD variable was examined as a continuous risk factor there was a 1.09 (9%), CI 0.95-1.25, increase in the adjusted OR for breast cancer per 100 unit (pglg lipid) increase in OCDD. No differences were found between cases and controls for the other six tested PCDDs. Mean concentration of TCDD was in the cases 3.6 (1.0-7.9) and in the controls 3.3 (1.1-6.3) pg/g lipid. For PCDFs no significant differences were found between cases and controls. The results were not changed if oestrogen or progesterone receptor status, S-phase fraction and DNA ploidy were considered. Breast tissue concentration of OCDD was increased in cancer patients, whereas the concentrations of other PCDDs and PCDFs were equal in cases and controls.

Menstrual and reproductive factors and biliary tract cancers

Abstract: The relationship between the risk of biliary tract cancers and menstrual and reproductive factors has been studied in a case-control study conducted in Milan, northern Italy, between January 1984 and February 1993 on 31 incident, histologically confirmed cases and 377 controls in hospital for acute, non-neoplastic, non-gynaecological, non-hormone-related conditions Odds ratios (ORs) together with their corresponding 95% confidence intervals (CIs) and the significance of the linear trends in risk were estimated by unconditional multiple logistic regression, after adjustment for age and cholelithiasis Menopause was associated with a decreased risk of biliary tract cancers (OR 02), while late menopause and the use of hormone replacement therapy tended to increase the risk (ORs 18 and 22 respectively) Age at menarche and regular menstrual cycles were not associated A trend in risk was found with parity, while total abortions and age at first and last birth were not related Thus, the protective effect of early menopause and the apparent association of multiple full-term pregnancies suggest a role of female hormones in the aetiology of biliary tract cancers

Breast size and breast cancer risk.

Abstract: The relationship between brassiere size, as an indicator of breast size, and breast cancer risk was considered in a case-control study conducted between 1991 and 1994 in six Italian centres. Cases were 2,557 women, below age 75, with histologically confirmed breast cancer, and controls were 2,566 women admitted to hospital for a wide spectrum of acute, non-neoplastic, non-hormone-related diseases. Odds ratios (ORs) of breast cancer and their 95% confidence intervals (CIs) were obtained from multiple logistic regression equations including terms for study centre and age, as well as main breast cancer risk factors. A slight inverse relationship was observed between breast size and the risk of breast cancer, with an OR of 1.37 (95% CI 1.05-1.80) for the smallest brassiere size compared with the largest; the increase in risk disappeared after adjustment for main recognized breast cancer risk factors, with an OR of 1.16 (95% CI 0.87-1.54) for brassiere size ≤ 1 compared with ≥ 5. No significant heterogeneity in risk of breast cancer with breast size was found in strata of age at diagnosis, parity, age at first birth, age at menopause, family history of breast cancer, benign breast disease, ever use of oral contraceptives and/or hormone replacement therapy. Thus, this study, based on a large number of caucasian women, provides conclusive evidence of a lack of appreciable association between breast size and breast cancer risk in this Italian population.

Mono- and bispecific single-chain antibody fragments for cancer therapy.

Abstract: Especially when dealing with solid cancers, single-chain antibody fragments (scFvs) have a lot of advantages. Due to their small size (27 kDa), these proteins clear more rapidly from the blood, and penetrate faster and deeper into tissues, than whole antibodies. Furthermore, the lack of constant regions ensures that they are not retained in tissues such as the liver and kidney. This reduces possible toxic side-effects. Single-chain construction is normally done by polymerase chain reaction (PCR). To decrease the overall cost of oligonucleotide primer synthesis, time-consuming primer design, multiple PCR reactions and individual PCR optimization, we designed a universal single-step overlap extension PCR protocol using hybridoma cDNA as a template. To overcome the lack of effector function, bispecific scFvs, consisting of an scFv produced against a tumour-associated antigen fused to a T cell marker-specific scFv, are being created, starting from already assembled scFv, by means of two additional PCR reactions. In this paper we describe both PCR methods that were successfully used to create scFvs against the human transferrin receptor, the human interleukin-2 receptor, the human CD3 molecule, a breast tumour-associated antigen and an anti-transferrin-anti-CD3 bispecific scFv.

Comparative descriptive epidemiology of oral and oesophageal cancers in Europe

Abstract: The two main determinants of oral and oesophageal cancer in Europe are alcohol and tobacco, and the two cancer sites show several similarities in their descriptive epidemiology. This study compares mortality from cancers of the oral cavity and oesophagus in European countries to evaluate similarities and differences. From official death certification numbers and population estimates, we obtained age-standardized rates for all ages and truncated (35-64 years). In most countries, rates for men tended to increase between 1955-59 and 1990-92 for both sites, although the increases were more marked for oral cancer. In the UK and Ireland, however, oral cancer decreased and oesophageal cancer increased, while in Finland and Iceland mortality for both sites decreased. The most striking increases were in Hungary, where the truncated rate in most recent calendar periods reached the highest levels in Europe. In France, rates for both cancers were extremely high : oral cancer increased from 1955-59 to the early 1980s, but started to decline afterwards. Mortality rates were much lower for women than men, and the correlation between the two sites was less marked. An age, period and cohort model, applied to the rates for men in selected European countries, suggested strong cohort effects for both cancers, generally more marked for oral cancer, with substantial increases in the cohorts born after 1920. The mortality rates of cancers of the oral cavity and oesophagus show several analogies, as expected from their relation to tobacco and alcohol ; but some discrepancies suggest that other, less well-identified, factors may also influence their rates and trends in Europe.