Showing papers in "International Journal of Cancer in 1990"

Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case-control study.

Abstract: The importance of age at menarche, age at menopause, height, and obesity as risk factors for breast cancer, and the possible interactions among these factors in breast cancer causation were investigated in a data set collected in the late 1960's, in an international multicenter case-control study. Multiple logistic regression procedures were used to model data from 3,993 breast cancer cases and 11,783 controls from 7 study centers representing the range of international variation of breast cancer incidence. Height and obesity (measured through the weight/height2 index) were independent risk factors for breast cancer among post-menopausal but not pre-menopausal women; post-menopausal women taller by 10 cm had a 12% higher risk of breast cancer (95% confidence interval, CI, 3-21%) and post-menopausal women of average height (say 158 cm) had an 11% higher risk of breast cancer (CI 7-16%) when they were heavier by 10 kg (and, therefore, more obese by 4 kg/m2). Age at menarche was a risk factor among both pre-menopausal and post-menopausal women, a delay of 2 years corresponding to a 10% reduction in breast cancer risk (CI 6-15%). Age at menopause was also a breast cancer risk factor, women with menopause at each 5 year age difference having a 17% higher risk of breast cancer (CI 11-22%). There is evidence of an interaction (deviation from the logistic regression-postulated multiplicativity) between obesity and age at menarche, implying that the protective effect of late menarche may not apply to overweight women or that late menarche may become detrimental in obese women. The estimated relative risk coefficients, when applied to average risk factor levels observed among control women, can explain only a small fraction of the difference in breast cancer incidence between Boston and Tokyo.

Age at first birth, parity and risk of breast cancer: a meta-analysis of 8 studies from the Nordic countries.

Abstract: Several large epidemiological studies in the Nordic countries have failed to confirm an association between age at first birth and breast cancer independent of parity. To assess whether lack of power or heterogeneity between the countries could explain this, a meta-analysis was performed of 8 population-based studies (3 cohort and 5 case-control) of breast cancer and reproductive variables in the Nordic countries, including a total of 5,568 cases. It confirmed that low parity and late age at first birth are significant and independent determinants of breast-cancer risk. Nulliparity was assoclated with a 30% increase in risk compared with parous women, and for every 2 births, the risk was reduced by about 16%. There was a significant trend of increasing risk with increasing age at first birth, women giving first birth after the age of 35 years having a 40% increased risk compared to those with a first birth before the age of 20 years. Tests for heterogeneity between studies were not significant for any of the examined variables. In the absence of bias, this suggests that several individual Nordic studies may have had too little power to detect the weak effect of age at first birth observed in the meta-analysis.

Patterns of expression of the p53 tumour suppressor in human breast tissues and tumours in situ and in vitro.

Abstract: An extensive series of histological sections reflecting the various states of normal breast tissue, and a range of benign and malignant lesions, were examined for the expression of the p53 protein using a panel of anti-p53 antibodies. In 2 separate series the results of using frozen or methacarn-fixed, paraffin-embedded sections were compared. Strong positive staining for p53 was detected in over 50% of the malignant lesions when frozen sections were used. This number fell to just over 20% when methacarn-fixed sections were examined. In neither series was any p53 staining seen in normal breast or in the benign lesions. Studies by Western blotting on breast cell lines confirmed that this histological signal is due to a pronounced over-expression of the p53 protein. Earlier studies show that this over-expression is associated with mutation of the p53 gene. Mutation of the p53 gene with over-expression of the mutant protein is therefore one of the most frequent specific genetic changes in malignant breast cancer.

Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China.

Abstract: To examine the geographic association between Helicobacter pylori infection and gastric cancer, we have assessed the prevalence of IgG antibodies to H. pylori in plasma samples taken in 1983 from 1882 men, aged 35-64 years, in 46 rural counties of the People's Republic of China. The gastric cancer mortality rates in these countries in 1973-75 varied from 3 per 1,000 (cumulative rate, 0-64 years) to 69 per 1,000, while the proportions of the population positive for H. pylori antibodies (based on an average of about 41 men per county) varied from 28% to 96%. After correction for the limited number of blood samples per county, the estimated correlation between H. pylori antibody prevalence and gastric cancer mortality was 40% (p = 0.02). No other type of cancer showed a significant association with H. pylori.

The 4th nation-wide study of adult T-cell leukemia/lymphoma (ATL) in Japan : estimates of risk of ATL and its geographical and clinical features

Abstract: To estimate the annual incidence of adult T-cell leukemia/lymphoma (ATL) by district in Japan, a large-scale nationwide survey of ATL and of non-Hodgkin's lymphoma was performed in 1988. Questionnaires for the registration of ATL and of T-cell and non-T-cell lymphoma were distributed to the physicians in charge of this survey in 1,287 hospitals with 200 or more beds throughout Japan. From the positive rate of anti-HTLV-I antibody in adults, the annual incidence of ATL was estimated at 697, independently of the present survey. In fact, 657 cases (47% of the estimated number), newly diagnosed during the 2 years January 1986 to December 1987, were registered from 191 general hospitals throughout Japan. Major results obtained from the present survey are as follows: (1) among all ATL cases registered, 51% were from Kyushu and 29% were from metropolitan areas (Kanto, Chubu and Kinki) and most, but not all, patients with ATL in the metropolitan areas had come from the ATL-endemic areas and settled in the metropolitan areas; (2) the estimated annual incidence rates of ATL per million adults were 40.4 in males and 26.4 in females in Kyushu, the overall risk of ATL being 1.5 times as high in males as in females; (3) the age-specific incidence rate in Kyushu increased steeply with age until the age of 70, and then decreased markedly in both sexes; (4) the ratio of T-cell versus non-T-cell lymphomas was 2.9 in Kyushu but 0.5 in other districts of Japan, however, this difference regressed to the average for the whole of Japan if ATL cases were excluded; (5) 26.5% of patients with ATL had a family history of cancer, and among these, 14 (8.2%) were ATL, 21 (12.2%) were lymphoma and 17 (9.9%) were hematopoietic malignancies, the incidence of which was markedly higher than in the general population; (6) with regard to clinicopathological features of ATL, there were more advanced cases in south Kyushu than in other districts, however, these differences were not statistically significant. To clarify the chronological changes and geographical variations in the annual incidence of ATL in Japan, continuous systematic nationwide surveillance is necessary and further nation-wide studies are being prepared.

Detection of EBV gene expression in Reed-Sternberg cells of Hodgkin's disease

Abstract: EBV DNA has been detected by Southern blot hybridization in 20-25% of Hodgkin's disease tumor specimens and localized to the Reed-Sternberg cells by in situ hybridization. In the present investigation we used a 3H-labelled EBER I anti-sense RNA for in situ hybridization of archival formalin-fixed paraffin-embedded Hodgkin's disease specimens previously shown by Southern Blot hybridization to be EBV-positive. In 6 of 8 specimens neoplastic cells showed an intense signal in virtually all of the tumor cells. The background lymphocytes, eosinophils, plasma cells and histiocytes did not demonstrate significant hybridization. In each case hybridization tended to spare the nucleoli. Hybridization was detected in specimens with histologies of mixed cellularity and nodular sclerosis. The intensity of signal relative to background is better than that in previous studies utilizing 35S-labelled large internal repeat probes for EBV in Reed-Sternberg cells. The exposure time is one week in contrast to the 4-5 weeks reported by others for detection of EBV in Hodgkin's disease. Both increased relative intensity and shorter exposure requirements may be attributed to the very high number of EBER transcripts in the target cells. The demonstration that EBER I is expressed is consistent with a role for EBV in growth regulation of Reed-Sternberg cells and suggests that the virus is not merely a silent passenger in Hodgkin's disease.

A population-based case-control study of colorectal cancer in majorca. I. Dietary factors

Abstract: A population-based case-control study was conducted between July 1984 and February 1988 in the Spanish island of Majorca; 286 incident colorectal cancer cases, 295 population controls and 203 hospital controls were interviewed using a food frequency questionnaire. In a multivariate analysis, an increased risk of colon cancer was found for high consumption of fresh meats (RR = 2.87) while a high consumption of cruciferous vegetables afforded protection (RR = 0.48). For rectal cancer an increased risk was associated with dairy products (RR = 3.08) while a protection was afforded by consumption of cruciferae (RR = 0.50). For colorectal cancer, the cereal food group also showed an increase in risk (RR = 1.92). When cases were compared to hospital controls, the effects of cruciferae in colon and rectum and those of dairy products in rectal cancer remained. The magnitude of the RR estimates was decreased for most comparisons, although in general terms the direction of the associations was the same. In addition, univariate analyses of food groups also suggested significant increases in risk of colorectal cancer for increasing consumption of cereals, potatoes, pastry, eggs and number of meals per day. An indication was found of a reduction in risk for consumers of coffee. An analysis based on risk scores was also conducted and a 4-fold increase in the risk of colorectal cancer and a highly significant statistical trend was found for high consumption of fresh meat, dairy products and cereals combined with low consumption of cruciferae.

Cytosolic NAD(P)H:(quinone-acceptor)oxidoreductase in human normal and tumor tissue : effects of cigarette smoking and alcohol

Abstract: NAD(P)H:(quinone-acceptor)oxidoreductase (QAO), previously known as DT-diaphorase, catalyzes the reduction of quinones to hydroquinones. Enhanced activity of the enzyme has been suggested to protect cells against the cellular toxicity and carcinogenicity of quinones, but may activate some cytotoxic anti-tumor quinones. Cytosolic levels of QAO, carbonyl reductase (CR) and total quinone reductase activity have been measured in normal and tumorous human tissues. QAO was the major component of the total cytosolic quinone reductase activity in all the tissues investigated. CR represented 10 to 28% of the total cytosolic quinone reductase activity in normal tissue. Normal tissue QAO was high in the stomach and kidney, and lower in the lung, liver, colon and breast. Primary tumor from lung, liver, colon and breast had elevated levels of QAO compared to normal tissue, while tumor from kidney and stomach had lower levels. CR was not significantly altered in tumor tissue, except in the case of lung and colon tumor which showed an increase compared to normal tissue. A major determinant of the variability of human lung tumor QAO was the cigarette-smoking history of the donor. Non-smokers and past smokers had high levels of tumor QAO compared to normal tissue. Smokers had levels of tumor QAO that were not significantly different from those of normal tissue QAO. Smokers had a small increase in normal lung QAO compared to non-smokers. Alcohol use was associated with an increase in lung tumor QAO but had no effect on QAO in normal lung. The function of QAO in tumors is not known but the elevated activity of QAO in some tumors and the apparent depressant effect of smoking could influence the response of these tumors to quinone drugs or toxic agents that are metabolized by QAO.

Lack of benefit from semi-annual screening for cancer of the lung : follow-up report of a randomized controlled trial on a population of high-risk males in Czechoslovakia

Abstract: Cigarette-smoking males (6,364), aged 40-64, were randomized into an intervention group which received 6-monthly screening by chest X-ray and sputum cytology, and a control group which received no asymptomatic investigation. After 3 years, both groups entered a follow-up period during which they received annual chest X-rays. Lung cancer cases detected by screening were identified at an earlier stage, more often resectable, and had a significantly better survival than "interval" cases diagnosed mainly because of symptoms. Comparison of the 2 groups showed a higher incidence of lung cancer in the intervention group, despite the follow-up period when both groups received annual examinations. There was no significant difference in mortality between the 2 groups.

Incidence and determinants of skin cancer in a high‐risk australian population

Abstract: In a Queensland community, we surveyed the incidence of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC), and associated risk factors. In December, 1986, 2,095 residents were examined by dermatologists for skin cancer. Of these, 1,770 further participated in a follow-up postal survey in December, 1987, regarding all skin cancers in the preceding 2 years, and 87 reported being treated for skin cancer in the 2-year period between December 1985 and November 1987. The estimated annual incidence rates of non-melanoma skin cancer in men and women aged 20-69 years were 2,389/100,000 and 1,908/100,000 respectively, with an overall ratio of BCC cases to SCC cases of 4.5 to one. While both tumour types occurred more commonly in fair-complexioned people, the risk associated with high sun exposure was greater for SCC than for BCC. Clinical signs of solar skin damage, especially the number of solar keratoses on the face, were the strongest predictors of both types of skin cancer.

Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues.

Abstract: The human homolog of the rat neu oncogene, HER2 (also termed c-erbB2) has been demonstrated in amplified form in human breast tumors with poor prognosis. Although amplification of the gene correlates with expression of a 185-kDa transmembrane glycoprotein, no extensive information is available regarding the extent of tissue and tumor specificity of this gene product. We have addressed this issue by immunohistochemically evaluating the expression of p185 HER2 in normal tissue and various tumors using monoclonal antibodies (MAbs) to distinct epitopes of its extracellular domain. No detectable levels of p185 HER2 were found in fetal tissues analyzed, with the exception of renal tubules in 2 out of 3 specimens tested and in intestinal epithelium. In adult tissues, detectable levels of this glycoprotein were found in a restricted number of cell types, the expression being heterogeneous among individuals and cell histotypes. Among the neoplasms assayed p185 HER2 was expressed in 46% of primary breast cancers, in 28% of ovarian tumors and in 30% of colon rectum malignancies. No male breast adenocarcinomas were p185-positive. A large number of other tumors tested revealed only a low incidence of expression of the p185. In metastatic breast tumors p185 HER2 was demonstrated homogeneously among multiple autologous lesions and almost invariably (80%) the expression of p185 in the primary lesion correlated with that of the deriving metastases. Our findings indicate that the expression of the p185 HER2 represents a tumor marker of clinical relevance in breast cancer. Whether this holds true for other malignancies remains to be explored.

A case-control study of gastric cancer and diet in Italy: II. Association with nutrients

Abstract: A case-control study involving interviews with 1,016 gastric cancer (GC) patients and 1,159 population-based controls in high- and low-risk areas was conducted to evaluate dietary factors and their contribution to the marked geographic variation in mortality from this cancer within Italy. Risks of GC were found to vary significantly with estimated nutrient intake. Risk rose with increasing consumption of nitrites and protein, and decreased in proportion to intake of ascorbic acid, beta-carotene, alpha-tocopherol, and vegetable fat. The associations with nitrite and beta-carotene tended to fade, however, in multivariate analyses adjusting for intake of other nutrients. Ascorbic acid showed the strongest geographic gradient, with highest consumption in low-risk areas. The findings suggest that the protective effects we previously reported for consumption of fresh fruit, fresh vegetables and olive oil may be linked to the vitamins C and E contained in these foods. The findings are consistent with the hypothesis that N-nitroso compounds are involved in GC risks, since elevated risks were apparent for agents (nitrites, protein) that promote nitrosation, while decreased risks were found for nutrients (ascorbic acid and alpha-tocopherol) which inhibit the process.

Loss of MHC class‐I expression in cervical carcinomas

Abstract: The expression of MHC class-I antigens was analysed in 67 cervical carcinoma biopsies; 16% of the biopsies showed complete or heterogeneous loss of HLA expression as judged by reactivity with antibodies recognizing monomorphic determinants of the class-I heavy chain bound to beta 2 microglobulin (beta 2m). In addition, other biopsies showed a loss in expression of particular allelic products: 23% for HLA-A2; 17% for HLA-A3; 23% for HLA-Bw4 and 19% for HLA-Bw6. Three biopsies showed changes at 2 alleles, 2 of which were at both HLA-A and -B loci. Down-regulation of class-I expression may be virally mediated and HPV DNA is frequently found in cervical carcinomas. However, there appeared to be no direct correlation between the detection of HPV 16 or 18 DNA in these tumours and changes in HLA expression. There was also no correlation with the expression of the oncofoetal antigen 5T4. Our results show that a significant proportion (at least 30%) of the cervical carcinomas showed some alteration in MHC class-I expression. Such changes may allow tumours to evade immune surveillance with more rapid progression. There was, however, no correlation with tumour type, degree of differentiation or stage of disease at presentation.

Risk of pancreatic cancer in relation to medical history and the use of tobacco, alcohol and coffee.

Abstract: A population-based case-control study was conducted to examine the relationship between certain medical conditions, the use of tobacco, alcohol and coffee, and the incidence of pancreatic cancer. Cases (N = 148) were married men ages 20 through 74 years diagnosed with pancreatic cancer from July 1982 through June 1986. Controls (N = 188) were identified by random digit dialing. Wives, responding as surrogates for both cases and controls, were interviewed by telephone and completed, alone, a food frequency questionnaire. The risk of pancreatic cancer was increased in individuals with a history of diabetes or pancreatitis, and decreased in those with a history of tonsillectomy. Individuals who had ever smoked cigarettes were at elevated risk of disease. This excess risk was confined to current smokers, in whom the odds ratio was 3.2 (95% CI 1.8-5.7); the risk among former smokers resembled that in those who had never smoked. There was no excess risk of pancreatic cancer among those who had ever used other forms of tobacco, including pipe tobacco, cigars and chewing tobacco. After adjustment for demographic and dietary characteristics, there was no association between pancreatic cancer risk and the intake of coffee, beer, red wine, hard liquor or all alcohol combined; a slight reduction in risk was seen among those consuming white wine daily.

General primer-mediated polymerase chain reaction permits the detection of sequenced and still unsequenced human papillomavirus genotypes in cervical scrapes and carcinomas.

Abstract: A newly developed general primer-mediated polymerase chain reaction (GP-PCR) was used for the detection of a broad spectrum of Human Papilloma-virus (HPV) genotypes, including unsequenced types, in cytologically normal and abnormal cervical smears and in biopsies of cervical carcinomas. This PCR method used different general primer sets, located in strongly conserved E1 and L1 regions of the HPV genome. Comparison between results of GP-PCR and HPV-type-specific PCR (TS-PCR) revealed an increase in overall HPV prevalence to 25%, 80% and 88% in scrapes with normally, slightly and severely dysplastic cells, respectively. Unsequenced HPV types were detected in 11% of cytologically normal swabs and in up to 30% of scrapes with dysplastic cells. Further characterization showed that unsequenced types concern HPV 13, 30, 31, 45, 51 and some other, possibly unknown HPV types. More than 90% of carcinomas in situ and invasive cervical carcinomas contained HPV. In the latter, only HPV16 and HPV18 were present. HPV16 was most frequently found in both normal and dysplastic cells, the rate being highest in neoplastic tissue. These results indicate that GP-PCR is a powerful approach for detecting as yet uncharacterized HPV types associated with neoplastic transformation of cervical squamous cell epithelium.

The tumour spectrum in hereditary non-polyposis colorectal cancer: A study of 24 kindreds in the netherlands

Abstract: The hereditary colonic cancer syndrome without polyposis, hereditary non-polyposis colorectal cancer (HNPCC), is usually divided into 2 main categories: hereditary site-specific colorectal cancer (Lynch syndrome I) and colorectal cancer in association with other forms of cancer (Lynch syndrome II). One problem associated with Lynch II is the uncertainty as to which types of cancer form part of the hereditary tumour spectrum. The present study was performed to obtain more information about the tumour spectrum of HNPCC. In the 24 HNPCC families studied, 104 patients had colorectal cancer (mean age at diagnosis: 46 years) and in 4 of the families this was the only type of cancer to occur. Sixty-five extra-colonic tumours were diagnosed in 20 families. Endometrial carcinoma was found in 16 patients belonging to 12 families. Cancer of the stomach occurred in 10 patients representing 5 families, and mainly in the older generations. Urinary-tract tumours were found in 8 patients from 4 families. Second primary tumours were diagnosed in 13 of the 16 patients with endometrial cancer, in 4 of the 10 patients with stomach cancer and in 7 of the 8 patients with a urinary-tract tumour. Many other types of carcinoma were found as well, but less frequently. In our families, the trait appears to be transmitted by patients with cancer of the stomach, endometrium or urinary tract, because some of their children have developed colorectal cancer. The findings suggest that, in these 24 HNPCC families, carcinomas of the endometrium, stomach and urinary tract belong to the hereditary tumour spectrum. Definite assignment of tumours to this spectrum will become possible only after a sensitive and specific biomarker becomes available. The screening programme should depend on which and how many extra-colonic tumours occur in a family.

Metallothionein gene expression and resistance to cisplatin in human ovarian cancer.

Abstract: Intracellular thiols have been proposed as mediators of resistance to alkylating agents and cisplatin. As metallothionein is the predominant protein thiol, we examined its relationship to cisplatin resistance in human ovarian cancer cell lines. A human ovarian carcinoma cell line, A2780, derived from an untreated patient, was treated with cisplatin in several ways and the induced resistance to cisplatin ranged from 13- to 68-fold. The degree of resistance was dependent upon the method of selection. The drug-resistant cell lines also developed low levels of cross-resistance to cadmium. Additional cell lines established from untreated patients or ovarian cancer patients refractory to cisplatin- and/or carboplatin-containing combination chemotherapy were studied. The most cisplatin-resistant cell lines, OVCAR-8 and -10, were from patients previously treated with intensive chemotherapy. OVCAR-8 was relatively cross-resistant to cadmium while OVCAR-10 appeared relatively sensitive. Cell lines were examined for expression of metallothionein mRNA to evaluate the relationship between cisplatin resistance, cadmium cross-resistance and metallothionein expression. Only two of the cell lines with in vitro-induced resistance to cisplatin, 2780E80 and 2780CP70B3, had detectable metallothionein mRNA. The other cell lines selected in vitro for cisplatin resistance, as well as the parental A2780 ovarian cancer cell line, showed no expression at our level of detection. There was variable expression of metallothionein among the OVCAR cell lines. Cell lines from untreated patients, OVCAR-5 and -7, did express metallothionein, while the most cisplatin-resistant cell lines, OVCAR-8 and -10, did not. We also examined cisplatin induction of metallothionein mRNA in the cell lines. Only 2780CP70B3 among the cell lines with in vitro-induced cisplatin resistance showed increased expression after short-term exposure to cisplatin. OVCAR-4 also had a slight increase in expression after exposure to cisplatin. Mouse C127 cells transfected with a bovine papilloma virus-metallothionein gene construct were compared for cisplatin sensitivity to the same cell type transfected with bovine papilloma virus alone. In this model system, metallothionein expression did not influence cisplatin cytotoxicity. On the basis of these studies, we conclude that there is no causal relationship between metallothionein expression and cisplatin resistance.

Evidence for the role of 34-kDa galactoside-binding lectin in transformation and metastasis.

Abstract: The endogenous M, 34,000 galaictoside-binding lectin (L-34) is found at elevated levels in a wilde variety of neoplastic cells and correlative evidence suggests that it is involved in tumor metastasis in vivo and in transformation in vitro. We demonstrate here that introduction of recombinant L-34 into tumorigenic, weakly metastatic UV-2237-cl- I 5 fibrosarcoma cells results in an increased incidence of experimental lung metastases in syngeneic and nude mice. Transfection of normal BALB/c-A3 I cloned fibroblasts with functional L-34 results in acquisition of anchorage-independent growth and in morphological transformation in vitro but not in tumorigenicity in vivo. These results provide direct evidence that the cellular expression of L-34 is associated with some aspects of transformation and with metastasis, but not with tumorigenicity per se.

Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells.

Abstract: The presence of carcinogen-DNA adducts in human tissues is evidence of exposure to carcinogens and may be an indicator of cancer risk. DNA was isolated from non-tumorous bronchial tissue of 37 cigarette smokers, 8 former smokers and 8 non-smokers and analyzed for the presence of aromatic and/or hydrophobic DNA adducts in the 32P-post-labelling assay. Adducts were detected as bands of radioactive material when 5'-32P-labelled deoxyribonucleoside 3',5'-bisphosphates were chromatographed on polyethyleneimine-cellulose tlc plates, and the patterns indicated the formation of adducts by a large number of compounds. Adduct levels detected in DNA from non-smokers, former smokers and current smokers were 3.45 +/- 1.62, 3.93 +/- 1.92 and 5.53 +/- 2.13 adducts/10(8) nucleotides, respectively. The differences in adduct levels between smokers and former and non-smokers were statistically significant (p less than 0.01); and among the smokers, significant correlations were found between adduct levels and both daily cigarette consumption and total cigarette consumption (daily consumption X number of years smoked). DNA was also isolated from the peripheral-blood leukocytes of 31 heavy smokers (greater than 20 cigarettes/day) and 20 non-smokers and analyzed by 32P-post-labelling. Adduct levels in the smokers' samples were not significantly different from levels in the non-smokers' samples (2.53 +/- 1.31 and 2.12 +/- 1.44 adducts/10(8) nucleotides, respectively). Thus, evidence for carcinogen exposure was found in human bronchial epithelium, a target tissue for tobacco-induced tumour formation, but not in peripheral-blood cells, indicating possible limitations in the use of the latter as a surrogate, non-target tissue source of DNA for monitoring human exposure to inhaled carcinogens.

Occupational and other non-dietary risk factors for nasopharyngeal carcinoma in Guangzhou, China.

Abstract: We conducted interviews on 306 histologically confirmed incident cases of nasopharyngeal carcinoma (NPC) occurring in residents of Guangzhou City, China, who were under the age of 50, and an equal number of age-, sex-, and neighborhood-matched controls. We also interviewed 110 mothers of patients under 45 and 139 mothers of controls who were matched to patients under age 45, to obtain information on childhood exposures of study subjects. Occupational exposure to products of combustion (RR = 2.4, p = 0.001) and cotton dust (RR = 0.3, P = 0.01) was independently related to risk of NPC. Use of tobacco products showed a moderate association with NPC; a lifetime exposure of 30+ pack-year equivalents conferred a 2-fold increased risk. A history of chronic ear or nose condition (rhinitis, sinusitis, nasal polyp, otitis media) was another risk factor for NPC (RR = 2.2, p less than 0.0005), and 18 cases compared to 3 controls had a first-degree relative with NPC (RR = 6.0, p = 0.001).

Vitamin A supplements, fried foods, fat and urothelial cancer. A case-referent study in Stockholm in 1985-87.

Abstract: In a population-based case-referent study of urothelial cancer in Stockholm during 1985-87, information was obtained from 78% of 418 identified cases and 77% of 511 selected referents. The relative risk (with 95% confidence interval) for intake of vitamin A supplements was 0.5 (0.2–1.0), with a dose-response relationship with increasing frequency of consumption. Increased risks of urothelial cancer were seen for several fried foods, for example fried meat [relative risk 1.4 (1.0–1.8) for weekly intake] and fried potatoes [relative risk 1.6(1.1–2.6) for weekly intake]. Subjects with a high intake of fried foods, as defined by a collapsed variable, had a relative risk of 2.4 (1.4–4.2). A dose-response relationship was also seen with an increasing average daily intake of fat [relative risk 1.7 (1.0–2.8) in the highest quintile], but adjusting for fried foods decreased the relative risk, and it is uncertain whether the adjustment allowed for residual confounding. No association was noted for meat other than fried, but the analysis was based on small numbers.

Dietary factors and breast-cancer risk in Denmark

Abstract: The influence of dietary factors, in particular the intake of fat and beta-carotene, on breast-cancer risk was evaluated in a case-control study including 1,486 breast cancer cases diagnosed over a 1 year period in Denmark. The control group was an age-stratified random sample of 1,336 women from the general population. Data on usual diet prior to the breast cancer diagnosis were collected by self-administered questionnaires of the semi-quantitative food frequency type. A highly significant trend (p less than 0.001) of increasing risk was observed with increasing fat intake, the RR for the highest quartile being 1.45 (95% Cl 1.17-1.80) compared with the lowest. However, information was not available to allow adjustment for the possible confounding effect of energy intake. The risk of breast cancer was not associated with consumption of vegetables rich in beta-carotene, multi-vitamin tablets or other dietary supplements, coffee, tea, sugar or artificial sweeteners.

Somatostatin receptor incidence and distribution in breast cancer using receptor autoradiography: relationship to EGF receptors.

Abstract: Somatostatin receptors (SS-R) were measured with in vitro receptor autoradiography using the SS analog 125I-[Tyr3]-SMS 201-995 as radioligand in 342 breast-tumor samples. In a group of 158 "small" tumor samples (mean section surface: 14 mm2 +/- 0.4; mean +/- SEM), 34 tumors (21%) were SS-R positive. In a group of 72 "large" tumor samples (mean size: 180 mm2 +/- 8; mean +/- SEM), 33 tumors (46%) were SS-R positive. In this second group, more than half of the tumors had a non-homogeneous distribution of SS-R, i.e., tumor regions within SS-R positive tumors were SS-R negative. In a group of 48 additional patients, we could show that primaries and their metastases, or double primaries from right and left breasts, or 2 primaries resected consecutively, could both occasionally be SS-R positive. Finally, in 71 SS-R-positive primary tumors, 18 tumor samples were found to have simultaneously Epidermal Growth Factor receptors (EGF-R); in 12 of these 18 cases, the 2 receptor types were not topographically overlapping. Whereas SS-R were located on tumor tissue, EGF-R were often seen on adjacent normal lobules and ducts. These results show that a subgroup of breast tumors contain SS-R, in several cases non-homogeneously distributed. Their location does not coincide with that of EGF-R. Metastasis of SS-R-positive primaries may be SS-R-positive, as are sometimes second primaries. For evaluation of SS-R incidence and distribution, autoradiography is of advantage, specially if it is performed on large tumor samples, since it allows precise identification of the tissue elements containing these receptors.

Dietary factors and risk of pancreatic cancer: Results of a Canadian population-based case-control study

Abstract: Dietary information from a case-control study of pancreatic cancer conducted in Metropolitan Toronto between 1983 and 1986 is reported. A total of 249 cases and 505 population-based controls completed quantitative diet histories from which total caloric intake and the intake of a number of nutrients were estimated. A positive association with total caloric intake was observed with a relative risk of 2.39, 95% confidence interval 1.18-4.83 (highest versus lowest quartile), due primarily to the intake of carbohydrates. Inverse associations were seen with fibre from fruit, vegetable and cereal sources, with a relative of risk of 0.42, 0.22-0.78 (highest versus lowest quartile), for total fibre intake.

4. The role of the epidermal growth factor receptor and the c‐erbB‐2 protein in breast cancer

Abstract: Breast cancer cells are derived from epithelial cells lining the ducts of the breast One of the fundamental characteristics that distinguish tumour cells from normal cells is that cancer cells grow in an apparently unregulated way Understanding the mechanisms that regulate the growth and differentiation of normal breast epithelial cells and the differences between these systems in cancer cells is one of the central goals of research into the cell biology of breast cancer

Intraperitoneal radio‐localization of tumors pre‐targeted by biotinylated monoclonal antibodies

Abstract: We describe 2-step and 3-step strategies for intraperitoneal tumor radio-localization by means of monoclonal antibodies (MAbs). Nude mice bearing intraperitoneal human colon carcinoma tumors were injected i.p. with biotinylated MAb AUAI, followed 24 hr later by radioiodinated streptavidin (2-step). The uptake of radioactivity in tumor and normal tissues was measured 4 hr after injection of radioactive compound. A 3-step strategy consisted in administering biotinylated antibody, cold avidin after 24 hr and 111In-labelled biotin after a further 4 hr; mice were then killed 2 hr later. Tumor localization of intraperitoneally-administered biotinylated antibody and direct targeting of radioactive streptavidin to biotinylated antibody bound to tumor sites were demonstrated using immunohistochemistry and autoradiography. Our results show that (i) the 2-step approach increased the percentage of radioactivity uptake by tumor with respect to directly labelled antibodies (24% vs. 6%) and improved the tumor/non-tumor ratio; (ii) the 3-step approach allowed faster blood clearance of the radioactive probe (111In-biotin) and yielded high tumor/non-tumor ratios. "Pre-targeting" methods appear to have advantages over the conventional 1-step approach with directly radiolabelled antibody.

Human papillomavirus (HPV) DNA in esophageal precancer lesions and squamous cell carcinomas from China

Abstract: A series of 51 biopsies derived from the same number of patients with established invasive squamous-cell carcinoma of the esophagus in Linxian, a high-risk area for esophageal cancer in China, were analyzed histologically and by in situ DNA hybridization to demonstrate human papillomavirus (HPV) infection. Epithelial changes suggesting HPV infection within or adjacent to the carcinoma lesions were found in 25 cases (49.0%). Esophageal lesions with HPV morphology showed both flat (25 cases) and inverted condylomas (2 cases) resembling those found in the genital tract. HPV 6, 11, 16 or 18 DNA sequences were detected in 22/51 (43.1%) of the esophageal specimens. HPV DNA was most frequently localized in epithelium adjacent to carcinomas in areas showing either epithelial hyperplasia (36.1%) or dysplasia (22.2%). Of the lesions with morphological HPV changes, 64% (16/22) were shown to contain HPV DNA. In 2 specimens, HPV DNA was found in frankly malignant cells. High-risk types HPV 16 and/or 18 DNA sequences were found in 16 of the 22 HPV DNA-positive cases (72.7%). Our results confirm previously reported HPV involvement in esophageal squamous-cell lesions, and support the hypothesis of HPV as a possible etiological agent in esophageal carcinogenesis.

Overexpression of the mdr1 gene in blast cells from patients with acute myelocytic leukemia is associated with decreased anthracycline accumulation that can be restored by cyclosporin-A.

Abstract: Typical multi-drug resistance (MDR) in human and animal cell lines is caused by overactivity of a unidirectional drug efflux pump. This pump is composed of a 170-kDa transmembrane glycoprotein (P-glycoprotein) that is encoded by the so-called mdr1 gene. The functionally relevant characteristic of MDR cells is a defect in drug accumulation that can be restored by agents which inhibit the P-glycoprotein pump. The purpose of our study was to find out whether P-glycoprotein inhibitors could increase the daunorubicin (DNR) accumulation in acute myelocytic leukemia (AML) cells, overexpressing the mdr1 gene. Using dot blot analysis with an mdr1-specific cDNA probe, we identified leukemic cell samples, obtained from chemotherapy-resistant AML patients, that had relatively high levels of mdr1 expression. These leukemic cells showed a reduced ability to accumulate DNR in vitro, as quantitated by flow cytometry. Addition of cyclosporin-A (Cy-A), a drug known to inhibit the P-glycoprotein pump, to the incubation medium resulted in an increase (up to 60%) in steady-state drug uptake by the leukemic cells. The degree of Cy-A-induced increase in drug accumulation in the leukemic cells correlated approximately with the level of overexpression of the mdr1 gene. Our data indicate that Cy-A is a good candidate for combination chemotherapy with cytotoxic drugs in clinical trials, aimed at the treatment of drug resistance in AML.

Diet, body mass and colorectal cancer: a case-referent study in Stockholm.

Abstract: A population-based case-referent study on diet (total energy, protein, fat, dietary fiber), body mass and colorectal cancer was performed in Stockholm in 1986–1988. The study included 1,081 subjects. The relative risks (RR, with a 95% confidence interval, highest versus lowest quintile) for colon cancer were as follows: total energy (1.7, 1. 0–3.0), protein (2.4, 1.5–4.0), total fat (2.2, 1.3–3.6), dietary fiber for men (0.5, 0.2–1.1), dietary fiber for women (1.2, 0.7–2.3) and body mass (2.0, 1.3–3.1). The relative risks for rectal cancer were: total energy (2.4, 1.2–4.7), protein (3.6, 2.0–6.4), total fat (2.5, 1.4 4.6), dietary fiber (0.5, 0.3–0.9), body mass for men (1.7, 0.7–4.0), and body mass for women (1.0, 0.5–1.9). Adjustment for physical activity, body mass (in the diet analysis), the abovementioned dietary factors (in the body mass analysis), and browned meat surface had little or no influence on the results.