Parity and the risk of pancreatic cancer: a nested case-control study

Three unusual cases of small-size leiomyosarcoma of the perirenal space were studied with CT. The renal capsule has been proved to be the origin of this type of tumor. A CT examination is accurate in suggesting the site of origin and excluding a renal cell carcinoma. However, unless evidence of invasion is noted, it is impossible on CT features to discriminate leiomyosarcoma from a benign leiomyoma.     

Avian exposure and risk of lung cancer in women in Missouri: population based case-control study

OBJECTIVE: To investigate the association, previously reported in three European studies, between ownership of pet birds and the risk of lung cancer. DESIGN: A population based case-control study with a structured questionnaire administered by telephone. SETTING: Missouri, a midwestern state in the United States with a population of about 5 million. SUBJECTS: All newly diagnosed cases of primary lung cancer in women aged 30-84 years in Missouri from 1 January 1993 to 31 January 1994 reported to the state cancer registry were invited to participate (n = 652); and 629 population based controls. MAIN OUTCOME MEASURES: Odds ratios were computed in relation to whether or not the study subject ever kept pet birds, the type of bird kept, and several measures of intensity or duration of exposure. Odds ratios were adjusted for smoking. RESULTS: The odds ratio (95% confidence interval) for the development of lung cancer associated with keeping pet birds was 0.84 (0.65 to 1.09). The results were similar for the type of pet bird kept, the number of birds kept, the location of the bird in the house, and the duration of ownership. CONCLUSION: The keeping of pet birds carries no excess risk for the development of lung cancer.     

Dietary nitrosodimethylamine and the risk of lung cancer: a case-control study from Uruguay

Evidence from animal studies indicates that various N-nitroso compounds are carcinogenic. We investigated whether consumption of nitrosodimethylamine (NDMA) and foods and beverages containing NDMA are carcinogenic for the lung. In a hospital-based case-control study in Uruguay, dietary intake of NDMA and its food sources was measured in 320 cases of lung cancer and 320 controls afflicted with diseases not related with tobacco use and diet. After adjusting for tobacco smoking and total energy intake, NDMA displayed a significant dose-response pattern, with a 3-fold increase in risk for the higher category of intake. The risks were slightly more elevated for adenocarcinoma of the lung. Also, salted meat consumption and beer intake were associated with an increased risk of lung cancer.     

Residential radon exposure and lung cancer among nonsmoking women

BACKGROUND: Radon at sufficiently high concentrations is known to cause lung cancer among underground miners and in experimental laboratory animals. PURPOSE: Our aim was to determine whether indoor levels of radon are associated with a detectable increase in lung cancer. Nonsmoking women were selected because they offer the best opportunity to detect radon-related risk while minimizing the potentially confounding influences of cigarette smoking and occupation. METHODS: A population-based, case-control study of incident lung cancer was conducted in Missouri. A total of 538 non-smoking white women diagnosed with lung cancer between 1986 and 1992 and 1183 age-matched control subjects were identified from the Missouri Cancer Registry and from driver's license and Medicare listings, respectively. Information on lung cancer risk factors was obtained by telephone interview. Year-long radon measurements were sought in every dwelling occupied for the previous 5-30 years. RESULTS: Radon measurements covered 78% of the relevant residential period, and women reported being indoors for 84% of this time. The time-weighted average radon concentrations were exactly the same for case subjects and control subjects (1.82 pCi/L of air [pCi L-1]). Radon levels greater than 4 pCi L-1 were experienced by 6.5% of the case subjects and 6.8% of the control subjects. For all data combined, there was little evidence for a trend of lung cancer with increasing radon concentrations (two-tailed trend test, P = .99 continuous data analysis; P = .19 categorical data analysis). A positive dose-response trend was suggested for the adenocarcinoma cell type and among directly interviewed women (two-tailed trend test; P = .31 continuous data analysis; P = .04 categorical data analysis), but not for other histologies or among those who had surrogate interviews. CONCLUSIONS: The possibility of detecting a risk from indoor radon in this study was maximized by (a) including a large number of nonsmoking women with high indoor occupancy, (b) conducting a large number of radon measurements near the time of the diagnosis of cancer, and (c) controlling for known causes of lung cancer. However, an association between lung cancer and the exposure to domestic levels of radon was not convincingly demonstrated. IMPLICATIONS: The magnitude of the lung cancer risk from radon levels commonly found in U.S. dwellings appears low.     

Lifestyle factors and prostate cancer risk: a case-control study in Sweden

We examined associations between lifestyle factors and subsequent risk of prostate cancer in a population-based case-control study. Information on smoking and alcohol habits, socioeconomic factors, marital status, family history, and sexual habits were obtained from a questionnaire and a face-to-face interview with 256 (74.6%) eligible patients and 252 (76.6%) selected controls, frequency matched by age and screened for prostate cancer with negative findings. Unconditional logistic regression was used to estimate the odds ratios (ORs). Risk was elevated among current smokers of cigarettes (OR, 1.8) and current users of hard liquor (OR, 1.4); however, the lack of dose-response trend for both of these exposures argues against a causal association. We found tentative evidence that early first intercourse, a larger number of sexual partners, and other indices of high sexual activity are associated with increased risk. Similarly, adult height, an indicator of nutrition during childhood and adolescence, was weakly positively associated with risk, although larger studies are needed to establish this link. Unmarried men had a lower risk than married men (OR, 0.3), and socioeconomic status did not appear to be strongly associated with prostate cancer. Men with a father who had prostate cancer had a more than 2-fold increased risk of prostate cancer, whereas those with a brother affected had about a 5-folk risk.     

Mechanistic model predicts a U-shaped relation of radon exposure to lung cancer risk reflected in combined occupational and US residential data

A mechanistically based cytodynamic two-stage (CD2) cancer model was shown recently to predict both ecologic US county data and underground-miner data on lung-cancer mortality (LCM) vs radon concentration, indicating biological plausibility of the apparent negative dose-response relation exhibited by the ecologic data. To further investigate this hypothesis, the CD2 model was fitted to combine age-specific LCM data vs estimated radon-exposure in white females of age 40+ years in 2821 US counties during 1950-1954 using new estimates of county-specific mean residential radon exposure, and in five cohorts of underground nonsmoking miners. The negative association of radon levels and corresponding county-level LCM rates apparent in women dying in 1950-1954 (11% of whom never smoked) was also apparent in women of age 60+ years (5% of whom never smoked). The CD2 fit obtained to the combined residential and occupational data was found to predict the combined data using biologically plausible parameter values, and also to predict inverse dose-rate effects exhibited in nonsmoking miner data to which the CD2 model was not fit. These results are consistent with the hypothesis that residential radon exposure has a nonlinear U-shaped relation to LCM risk, and that current linear extrapolation models substantially overestimate such risk.     

Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis

BACKGROUND: This study was performed to analyze the reasons for conversion of laparoscopic colorectal procedures to open surgery and to identify risk factors. METHODS: All patients who underwent laparoscopic colorectal surgery at our institution were enrolled in a prospective trial. The causes of conversion were analyzed. Statistical analysis, including a logistic regression model, was performed to identify factors that would predict an increased risk of conversion. RESULTS: A total of 300 laparoscopic or laparoscopic-assisted procedures for both benign and malignant diseases were performed within 5 years. Mean patient age was 61.4 years (range, 17-93). There were 218 women and 82 men. Major complications occurred in 8.6%, and 30-day-mortality rate was 1.1%. Postoperative hospitalization was 13.9 days (range, 6-47). Conversion occurred in 22 cases (7.3%). The mean age of the converted group was 64.7 years (range, 31-93). Postoperative hospital stay was 15.0 days (range, 10-25). The main reasons for conversion to open surgery were inflammation, obesity, anesthetic problems, technical difficulties, intraoperative complications, and intraoperative decisions concerning oncological resection. The conversion rate was 14.6% in patients who underwent sigmoid resection for diverticular disease. By univariate analysis, statistically significant factors defining a higher risk of conversion were male gender (p = 0.0029), age from 55 to 64 years (p = 0.0015), extreme body status (p = 0.0001), and diagnosis of diverticular disease (p = 0.0011). According to the logistic regression model, all four factors combined would give a probability of conversion of 70.3%. CONCLUSIONS: The risk factors contributing to the possibility of conversion included male gender, age between 55 and 64 years, extreme body status, and diverticular disease. Using these data, patients with an increased likelihood of conversion can be identified. However, if conversion is necessary, laparoscopic colorectal surgery can be safely applied to the patients with no additional morbidity.     

Alcohol consumption and risk of breast cancer: a multicentre Italian case-control study

The relationship between alcohol consumption and breast cancer risk was investigated using data from a co-operative case-control study conducted in Italy between 1991 and 1994 on 2569 incident, histologically confirmed breast cancer cases and 2588 controls in hospital for acute, non-neoplastic, non-hormone related conditions. Overall, 915 (38%) cases and 1048 (43%) controls were abstainers. Compared with them, the odds ratio (OR), adjusted only for age, was 1.31 (95% confidence interval (CI) 1.13-1.53) for drinkers and became 1.39 (95% CI 1.(1)21-1.60) after correction for measurement error. The multivariate OR was 1.21 for drinkers of < or = 5.87 g/day and 1.23, 1.19, 1.21, 1.41 for drinkers of 5.88-13.40, 13.41-24.55, 24.56-27.60, > 27.60 g/day, respectively. The trend in risk was significant (chi 2 = 12.28, P < 0.0005). The association was apparently stronger in premenopausal women (OR = 1.80 for > 27.60 g/day). Considering the different types of alcoholic beverages (wine, beer, digestives, grappa and other spirits), a significant direct trend in breast cancer risk was seen for wine with an OR of 1.27 (95% CI 1.06-1.53) for the category > 26.34 g/day. The ORs were also above unity for beer, grappa, digestives and spirits drinkers. No appreciable interaction was observed between alcohol drinking and body mass index, smoking, or any other covariate considered. Thus, the present data, based on a validated alcohol consumption questionnaire and on a population characterised by a relatively high alcohol consumption in women, confirmed that alcohol drinking is moderately related to breast cancer risk. If causal, this association could explain 12% (95% CI, 5-19%) of breast cancers in Italy, thus representing one of the major avoidable risk factor for breast cancer.     

Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico

Some, but not all, epidemiological studies have suggested that dichlorodiphenyltrichloroethane (DDT) may play a role in the development of breast cancer. These investigations have been conducted in countries where this substance has been banned for at least 20 years. We conducted a study in Mexico, a country in which DDT is still being used to control malaria. In a hospital-based case-control study, we compared 141 histologically confirmed cases of breast cancer with 141 age-matched controls (+/-3 years). All subjects were identified at three referral hospitals of Mexico City between March 1994 and April 1996. Reproductive histories and other variables were obtained by structured interviews, DDT/DDE levels were determined in serum by gas-liquid chromatography. The arithmetic mean of serum DDE in lipid basis was 562.48 +/- 676.18 ppb (range, 10.24-4661.44) for the cases and 505.46 +/- 567.22 ppb (range, 0.004 to 4361.75) for the controls, but this difference was not statistically significant. The age-adjusted odds ratios for breast cancer regarding the serum level of DDE were 0.69 (95% confidence interval, 0.38-1.24) and 0.97 (confidence interval, 0.55-1.70) for the contrasts between tertile 1 (lowest level) and tertiles 2 and 3, respectively. These estimates were unaffected by adjustment for body mass, accumulated time of breast-feeding and menopause, and other breast cancer risk factors. These results do not lend support to the hypothesis that DDT is causally related to breast cancer at the body-burden levels found in our study population but do not exclude the possibility that higher levels of exposure could still play a role in the etiology of this tumor.     

Breast cancer risk and alcohol consumption: results from a large case-control study

BACKGROUND: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk. METHODS: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking. RESULTS: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women.     

Helicobacter pylori infection and gastric cancer. A nested case-control study in a rural area of Japan

We conducted a seroepidemiological nested case-control study to determine the association of gastric cancer with Helicobacter pylori infection and atrophic gastritis. A cohort of 2858 participants in an annual multiphasic health check-up were followed for eight years. Data for 45 gastric cancer cases and 225 sex-, age-, and address-matched control subjects were analyzed. Helicobacter pylori infection was determined by IgG antibodies, and atrophic gastritis was diagnosed by both serum pepsinogen I level (< or = 70 ng/ml) and the pepsinogen I/II ratio (< or = 3.0). Univariate analysis showed that Helicobacter pylori and atrophic gastritis were significantly associated with gastric cancer. In a multivariate analysis, atrophic gastritis was associated with significantly increased risk of cancer (odds ratio, 3.38; 95% confidence interval, 1.54-7.42); however, Helicobacter pylori was not associated with cancer (odds ratio, 1.84; 95% confidence interval, 0.59-5.72). These results suggest that Helicobacter pylori infection alone is not directly associated with gastric carcinogenesis but has an indirect relation to gastric cancer through the development of atrophic gastritis.     

A nested case-control study of kidney cancer among refinery/petrochemical workers

Since permanently high levels of GnRH analogues are necessary to exert direct and/or indirect antitumor effect on mammary tumors, much emphasis was put on the development of retarded-release devices (e.g. microcapsules) for GnRH derivatives. Alternatively, these compounds can be covalently coupled to high-molecular mass carrier molecules for the design of bioconjugates acting as (a) prodrugs producing prolonged release or (b) macromolecular therapeutics. In order to evaluate the feasibility of this approach, a prototype construct has been prepared with a potent GnRH antagonist Ac(D-Trp1,3, D-Cpa2, D-Lys6, D-Ala10)-GnRH (MI-1544). As a carrier, a representative of a new generation of synthetic, biodegradable branched poly[Lys(Xi-DL-Alam)] (XAK) type polypeptides with poly(L-lysine) backbone has been used in which X is an acetylated derivative of glutamic acid (AcEAK). This polyanionic polypeptide with free gamma-carboxyl groups was conjugated to MI-1544, which has only a single amino group at position 6. In this paper, we describe (i) the synthesis and structure (primary structure, conformation) properties of the MI-1544-AcEAK conjugate with a 33% degree of substitution, (ii) the effect of the covalent attachment of MI-1544 to AcEAK on its blood clearance and tissue distribution, and (iii) the hormone-related indirect (ovulation inhibitory) or direct (antiproliferative) antitumor activity of the conjugate studied by in vitro assays. Data obtained with 111In- and 125I-labeled conjugates have demonstrated that in fact the body/blood survival of MI-1544 was prolonged by 1.5-3 times. The direct in vitro antitumor effect of MI-1544 was maintained or even enhanced in the MI-1544-AcEAK conjugate. Furthermore, we have shown that this conjugate was able to antagonize the effect of GnRH in vitro or to act as free MI-1544 both in short- and long-term inhibition of ovulation even after single subcutaneous injection. These data suggest that it is feasible to use a biodegradable polymeric polypeptide for development of a macromolecular therapeutic with GnRH antagonists.     

Differential exposure misclassification in case-control studies of environmental tobacco smoke and lung cancer

We review some of the literature on the effects of exposure misclassification on the statistical analysis of case-control studies. In particular, we focus on evidence for exposure misclassification which may be different for cases and controls in studies of environmental tobacco smoke (ETS). For example, such misclassification could induce relative risk estimates below unity for low exposure which appears to be the case in U.S. lung cancer and ETS studies. We describe procedures for systematically examining the sensitivity of dose-response statistics on exposure misclassification. The procedures demonstrate how p-values for the null hypothesis of no dose-response trend could be adjusted to account for exposure misclassification. The adjustment procedures were applied to an example based on a recently published large study of ETS and lung cancer in which a p-value for trend was reported as 0.03. In this example it is seen that modest differential exposure misclassification can induce substantial increases in the actual p-value, changing what appears to be statistically significant to decidedly nonsignificant.     

Anthropometric and other risk factors for ovarian cancer in a case-control study

Because it has been suggested that an environmental factor may play a role in the etiology of ovarian cancer, a case-control study was conducted to assess some environmental and other risk factors for ovarian cancer from 1994 to 1996 in northern Kyushu, Japan. We analyzed the data of 89 cases with epithelial ovarian cancer and 323 controls without any cancer or ovarian disorder. After controlling for the effect of potential confounders, the odds ratios of ovarian cancer across increasing quartiles of the heaviest body weight were 1.00, 1.15, 1.71, 2.29 (P = 0.008, test for trend). Significantly increased risks were noted for a history of diabetes mellitus (P < 0.05), and for a family history of ovarian cancer (P < 0.05). Significantly decreased trends for risk were obtained for the number of pregnancies (P < 0.01) and the number of live births (P < 0.001). This study provides additional support for an association between obesity and the risk of ovarian cancer. This relationship may at least partly explain the recent increase in the incidence of ovarian cancer in Japan, although possible contributions of other factors can not be ruled out.     

Mortality studies of machining fluid exposure in the automobile industry. IV: A case-control study of lung cancer

The taxanes represent a new class of clinical chemotherapeutic agents. A series of in vitro studies were independently of each other initiated in two different institutes (Amsterdam and Madison) to test the hypothesis that hyperthermia might enhance the cytotoxicity of taxanes. Clonogenic capacity experiments (Amsterdam) included the exposure of R1- and SW 1573-cells to 1, 4, or 24 h of paclitaxel with heat 43 degrees C x 60 min in the last hour of drug treatment or at 24, 48 as well as 72 h post drug treatment. Survival assay experiments (Madison) included the exposure of L-929-cells to paclitaxel and docetaxel for 24 h with heat 41.8 degrees C x 60 min the first or last hour of drug treatment as well as 24 and 48 h post treatment. No thermal enhancement of cytotoxicity for the taxanes was observed in these human and murine cell lines, with congruent data in both institutes. In addition, high performance liquid chromatography studies at 41.8 degrees C and 43 degrees C demonstrated paclitaxel and docetaxel were heat stable.     

Meat, fat and risk of breast cancer: a case-control study from Uruguay

To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.