Comparison between hospitalized and screening controls in studies assessing breast cancer risk.

BACKGROUND: In case-control studies, selection of an appropriate group of controls is a critical step which may affect the outcome of the analysis. METHODS: We studied the differences in reproductive, lifestyle, and anthropometric variables between controls from a hospital-based study and controls from a screening clinic. Odds ratios for breast cancer were calculated using the two types of controls, and the impact on the resulting odds ratio was studied. RESULTS: Some interesting differences in odds ratios obtained with the two sets of controls were found. Among premenopausal screening subjects, the odds ratio for breast cancer did not change across quartiles of body mass,while among hospital subjects, the risk of breast cancer significantly decreased with increasing body mass. For liquor and beer consumption, a three-fold increase in breast cancer risk was observed among premenopausal hospital subjects, whereas no association was found among screening subjects. Among postmenopausal women, a significant decrease in breast cancer risk with ovariectomy was only observed in the hospital-based study. CONCLUSIONS: Our results suggest that in examining the association between body mass, alcohol consumption, or ovariectomy and breast cancer risk, the choice of control group used should be carefully considered.

Smoking and lung cancer risk in American and Japanese men: an international case-control study.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

Cancer mortality in the United States and Germany.

PURPOSE: The USA and Germany are currently two of the world's leading industrial nations with comparable standards of living and considerable similarities in lifestyle. Fifty years ago, i.e., in the years following the Second World War, the living conditions in the two countries were completely different. If it is true that the major part of cancer occurrence is lifestyle-related, we should see corresponding discrepancies and assimilations on the level of cancer occurrence. METHODS: As an exercise in descriptive epidemiology, we compare the time trends in German and US cancer mortality in order to examine whether they parallel indeed the differences and changes in lifestyle factors of the two countries. RESULTS: Overall, we found the cancer mortality of the two countries converging to rather similar rates. However, in detail, the data indicate various inconsistencies between the patterns of lifestyle factors and cancer mortality in the two countries: similar lung cancer rates, despite rather different patterns of cigarette consumption, or decreasing rectal cancer mortality, despite increasing prevalence of risk factors, are examples. CONCLUSIONS: Promising changes with regard to relevant risk factors indicate that the recent decline of cancer mortality in both countries will continue. Nevertheless, vigorous action towards primary prevention in Germany and more effective screening programs in both countries appear recommendable.

Reevaluation of the confounding effect of cigarette smoking on the relationship between alcohol use and lung cancer risk, with larynx cancer used as a positive control.

BACKGROUND: The effect of smoking on lung cancer risk has been well documented, while the effect of alcohol remains controversial. We examined the hypothesis that the apparent association between alcohol intake and lung cancer risk is fully due to the confounding effect of cigarette smoke. METHODS: Our sample of hospitalized patients included 2,953 male and 1,622 female lung cancer cases; 521 male and 159 female larynx cancers cases; and 8,169 male and 4,154 female controls, admitted to participating hospitals between 1981 and 1994. All controls had been diagnosed with non-smoking-related diseases. Larynx cancer was used as a positive control for lung cancer. Relative risks were estimated through odds ratios, adjusted through multiple logistic regression. RESULTS: Although the odds ratios for alcohol had been significantly elevated prior to adjustment for smoking (OR = 2.4, 95% CI = 2.0-2.8), alcohol had no effect on lung cancer following this adjustment (OR = 1.2, 95% CI = 1.0-1.4). By contrast, the effect of alcohol on larynx cancer remained high even after adjustment for smoking (OR = 5.6, 95% CI = 3.7-8.6). CONCLUSION: The often-reported association between alcohol and lung cancer risk can be fully explained by the confounding effect of cigarette use.

Handheld cellular telephone use and risk of brain cancer.

CONTEXT: A relative paucity of data exist on the possible health effects of using cellular telephones. OBJECTIVE: To test the hypothesis that using handheld cellular telephones is related to the risk of primary brain cancer. DESIGN AND SETTING: Case-control study conducted in 5 US academic medical centers between 1994 and 1998 using a structured questionnaire. PATIENTS: A total of 469 men and women aged 18 to 80 years with primary brain cancer and 422 matched controls without brain cancer. MAIN OUTCOME MEASURE: Risk of brain cancer compared by use of handheld cellular telephones, in hours per month and years of use. RESULTS: The median monthly hours of use were 2.5 for cases and 2.2 for controls. Compared with patients who never used handheld cellular telephones, the multivariate odds ratio (OR) associated with regular past or current use was 0.85 (95% confidence interval [CI], 0.6-1.2). The OR for infrequent users (<0. 72 h/mo) was 1.0 (95% CI, 0.5-2.0) and for frequent users (>10.1 h/mo) was 0.7 (95% CI, 0.3-1.4). The mean duration of use was 2.8 years for cases and 2.7 years for controls; no association with brain cancer was observed according to duration of use (P =.54). In cases, cerebral tumors occurred more frequently on the same side of the head where cellular telephones had been used (26 vs 15 cases; P =.06), but in the cases with temporal lobe cancer a greater proportion of tumors occurred in the contralateral than ipsilateral side (9 vs 5 cases; P =.33). The OR was less than 1.0 for all histologic categories of brain cancer except for uncommon neuroepitheliomatous cancers (OR, 2.1; 95% CI, 0.9-4.7). CONCLUSIONS: Our data suggest that use of handheld cellular telephones is not associated with risk of brain cancer, but further studies are needed to account for longer induction periods, especially for slow-growing tumors with neuronal features.

Increased expression of cyclooxygenase-2 in rat lung tumors induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone: the impact of a high-fat diet.

Aberrant or excessive expression of cyclooxygenase (COX)-2 has been implicated in the pathogenesis of many disease processes, including carcinogenesis. COX-2 expression was immunohistochemically examined in archival samples (D. Hoffmann et al., Cancer Res., 53: 2758-2761, 1993) of lung neoplasms (adenomas, adenocarcinomas, and adenosquamous carcinomas) induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in male F344 rats that had been fed either a semipurified AIN-76A diet with high-fat (HF; 23.5% corn oil) or low-fat (LF; 5% corn oil) content. The intensity and extent of COX-2 positivity was graded from 0 (undetectable or negligible expression) to grades 1 (<30% expression), 2 (30-60% expression), 3 (60-90% expression), and 4 (>90% expression). The scoring criteria were similar to those used with specimens from human lung cancers (T. Hida et al., Cancer Res., 58: 3761-3764, 1998). In group 1 (NNK plus HF diet), adenomas, adenocarcinomas, and adenosquamous carcinomas were of mean grades 2, 3, and 4, respectively; in group 2 (NNK plus LF diet), the corresponding mean grades were 1, 1, and 3. Although control rats, given HF (group 3) or LF (group 4) diets but no NNK, developed spontaneous lung tumors, the expression of COX-2 was either negligible (one adenoma of grade 0 in group 3) or of a very low grade (one adenocarcinoma of grade 1 in group 4). In addition, the latency of the tumors in the peripheral lung in assays with NNK is significantly shorter in rats maintained on the HF diet than in those on LF diet. COX-2 expression was not evident in normal lung tissues. We report here for the first time that NNK induces increasingly higher levels of COX-2 expression with progressive stages of lung tumorigenesis when rats are fed the HF diet. The increase in COX-2 expression may be associated with the development of lung tumors induced by NNK. This well-defined animal model is valuable for studying modulation of COX-2 expression in lung carcinogenesis by various factors, including dietary components.

Oral enzyme therapy and experimental rat mammary tumor metastasis.

Although there has been much interest over the years in the medical use of orally administered proteolytic enzymes, there is considerable controversy about their efficacy against advanced stages of cancer. In light of this, the goal of the present study was to assess the inhibitory effects of different doses of an orally administered porcine pancreas preparation on the growth and metastasis of the R13762 transplantable rat mammary tumor. Five groups of 12 F-344 female retired breeders were inoculated orthotopically with a 2mm3 tumor implant and placed on the following diets: (1) AIN-76A diet + 20% porcine pancreas preparation (PPP); (2) AIN-76A + 20% PPP + 10 mg Mg citrate/rat/day; (3) AIN-76A + 2% PPP; (4) AIN-76A + 2% PPP + 10 mg Mg citrate and (5) AIN-76A only (control). Primary tumor development was monitored for 40 days and following sacrifice, lungs were excised, stained and metastatic foci quantitated. Metastatic foci were sorted into 3 groups based on their radii: small (<1mm), medium (1-3mm) and large (>3mm), and volumes calculated. The oral enzyme preparation had no effect on primary tumor growth or on body weight change over the duration of the study. The percent (incidence) of rats with pulmonary metastases among the five groups were not significantly different. However, among the three size categories of pulmonary foci, decreased incidence was found only in the large (>3mm) volume subset of the 2% PPP group supplemented with Mg++. When assessed in terms of mean number of pulmonary foci/rat, the 20% PPP group exhibited the highest and controls the lowest frequency with the important exception of the 2% PPP + Mg++ group (large volume) which exhibited the lowest frequency of all treatment groups. In general, the presence of Mg++ resulted in marked decreases in mean number of pulmonary foci/rat compared to groups fed PPP without the Mg++ supplement. Similar results were obtained when foci were quantitated in terms of metastatic volume rather than frequency. The results of this laboratory animal study suggest that to show effective inhibition of metastatic dissemination of the R13762 tumor by PPP, lower doses of PPP and larger numbers of animals, to account for the high variability in the model, will be required.

The past, present, and future of the prevention of lung cancer.

The article relates details of the history of research into the causal association of cigarette smoking and lung cancer on the basis of multidisciplinary studies that have explored the epidemiology, biology, chemistry, and biochemistry of tobacco carcinogenesis and research in behavioral sciences and health education that has sought to address one of our nation's foremost public health problems. Recalling past and present challenges and achievements in all of these areas, the author then outlines his vision for addressing this health problem in the future. This is laid out for various segments of the research community and for society as a whole, i.e., Cancer Centers and hospitals, epidemiologists, laboratory scientists, legislators, educators and behavioral scientists, and the media. It is proposed that for the current policy initiatives in tobacco-related cancer control to succeed, there needs to be a focus on preventing the initiation of tobacco use among children and adolescents. All segments of society can help to achieve this goal. In the nation's research planning, there needs to be a proper balance between basic and applied research, including research on and application of preventive principles, because cancer need not be an inevitable consequence of aging but is largely preventable.

Alcohol use and prostate cancer in U.S. whites: no association in a confirmatory study.

BACKGROUND: In a recent study among U.S. men with prostate cancer, alcohol consumption was associated with an increase in prostate cancer risk. This finding could have considerable public health implications. We therefore set out to confirm the reported association in a study of comparable scale, using the same alcohol exposure categories. METHODS: The association was evaluated in a case-control study of 699 white prostate cancer cases and 2,041 matched controls, admitted between 1977-1991 to 20 U.S. hospitals. RESULTS: No association was seen between prostate cancer and alcohol intake comparing ever, current, and former to never drinkers, not even for the highest reported level of alcohol consumption. CONCLUSIONS: Our failure to confirm the reported association agrees with the findings of most studies that, within a wide range of alcohol intake, there is no relation between alcohol consumption and prostate cancer. However, some studies suggest that alcoholics may have an increased prostate cancer risk. This needs further exploration.

A case/control study of risk factors for major salivary gland cancer.

BACKGROUND: Salivary gland cancer (SGC) is a rare disease with a largely unknown origin. Because cancer of the tongue and mouth floor is caused primarily by smoking and alcohol consumption, we investigated the role of tobacco, alcohol, and other possible risk factors in the development of SGC in a hospital-based study. METHODS: Interviews were obtained from 128 patients with newly diagnosed histologically confirmed SGC and from 114 age- and gender-matched controls by using a structured questionnaire. All patients were interviewed at bedside by a trained interviewer. RESULTS: No differences in levels of education were found between the two groups. Cigarette smoking and alcohol consumption did not independently or jointly increase the risk of SGC. Chewing tobacco and snuff use were also unrelated factors. The odds ratio for low body mass in men was 0.46 (p = 0.05). There was no relation with body mass in women. An examination of employment history and job-related exposures revealed no occupational risk factors. CONCLUSION: These findings show that smoking, alcohol consumption, and most occupational exposures are unrelated to SGC.

Lung cancer risk and workplace exposures in black men and women.

There are little data on workplace exposures and lung cancer risk in blacks. An ongoing case-control study of lung cancer that included 550 black men and women with lung cancer and 386 age-matched controls was examined by reported occupational exposures and job titles. In men, significant associations were observed with reported exposure to asbestos [odds ratio (OR), 1.8; 95% confidence intervals (CI) 1.03-3.1] and coal dust (OR, 2.8; 95% CI 1.1-7.0). Elevated but nonsignificant risks of 1.4 or more were detected for the following occupations: police/security guards, farmers/farm workers, laborers, and motor-vehicle drivers. In women, nonsignificant increased risks were found with reported exposure to paint (OR, 1.8) and gas fumes (OR, 4.9). Women employed as farmers/farm workers and building maintenance workers had elevated but nonsignificant risks.

Parakeets, canaries, finches, parrots and lung cancer: no association.

The relationship between pet bird keeping and lung cancer according to exposure to tobacco smoking was investigated in a case-control study in hospitals of New York City and Washington, DC, USA. Newly diagnosed lung cancer cases (n = 887) aged 40-79 years were compared with 1350 controls with diseases not related to smoking, of the same age, gender and date of admission as the cases. The prevalence of pet bird keeping was 12.5% in men and 19.1% in women. There was no association between ever keeping a pet bird and lung cancer in never smokers (men adjusted odds ratio (OR) = 0.70, 95% confidence interval (CI) 0.15-3.17; women, 1.32, 95% CI 0.65-2.70), or in smokers and non-smokers combined, after adjustment for ever smoking (men: 1.28, 95% CI 0.88-1.86; women: 1.17, 95% CI 0.83-1.64; all: 1.21, 95% CI 0.95-1.56). Risk did not increase in relation to duration of pet bird keeping. Cases and controls kept similar types of birds. There was a tenfold increase of lung cancer risk associated with smoking among non-bird keepers (adjusted OR = 9.15). There was no indication of a synergism, either additive or multiplicative, between smoking and pet bird keeping with respect to lung cancer risk. Either alone or in conjunction with smoking, keeping parakeets, canaries, finches or parrots is not a risk factor for lung cancer among hospital patients in New York and in Washington, DC.

Smoking trends in the United States between 1969 and 1995 based on patients hospitalized with non-smoking-related diseases.

BACKGROUND: This study examines smoking trends in the United States by race, gender, education, and occupation. METHODS: The data were collected between 1969 and 1995 through a hospital-based case-control study on tobacco-related cancers, including 21,057 male and 14,448 female control subjects who had been diagnosed of non-smoking-related diseases. Smoking measures were adjusted through direct standardization and regression methods. RESULTS: Despite the decline in smoking, daily cigarette consumption remained high among current smokers. Women's smoking prevalence decreased more slowly than men's and their age at smoking initiation also declined, while the inverse effects on smoking by education and occupation were more pronounced in men than in women. Smoking prevalence was higher, but daily cigarette consumption was lower in blacks compared to caucasians. CONCLUSIONS: Despite an overall downward trend in smoking, lung cancer remains a major public health concern, particularly among women, blacks, and white men with low education. The development of a systematic mechanism for more detailed, regular monitoring of tobacco use by various subpopulations is, therefore, crucial to future public health planning.

Tobacco as a cause of lung cancer: some reflections.

PIP: This is a historical review of the long effort to establish the link between cigarette smoking and lung cancer. The author examines why it was so difficult to attract attention to the vital scientific and public health issues inherent in this linkage, focusing on the apathy of the health professionals concerned and their reasons for not accepting or promoting the evidence relating lung cancer to smoking.^ieng

Cigarette smoking and prostate cancer: no relation with six measures of lifetime smoking habits in a large case-control study among U.S. whites.

BACKGROUND: The study was undertaken to describe the association between lifetime cigarette smoking habits and prostate cancer. Whereas most case-control and cohort studies report no association, the positive findings from some large cohort studies are difficult to ignore. The available information on lifetime smoking habits from most studies is limited however. METHODS: In a study of 1,097 prostate cancer cases and 3,250 matched controls, admitted between 1969 and 1991 to U.S. hospitals, several ordinal measures of lifetime smoking were compared to look for dose-response or threshold associations. RESULTS: No association was seen between prostate cancer and former or current smoking, age started smoking, number of years smoked, cigarettes per day smoked, the number of years since quitting, and lifetime tar exposure. CONCLUSIONS: Our data provide the most complete dose-response smoking information to date, and support the findings from the majority of studies that prostate cancer is not associated with cigarette smoking.

Risk of squamous cell carcinoma and adenocarcinoma of the lung in relation to lifetime filter cigarette smoking.

BACKGROUND: Over the past few decades, the incidence of adenocarcinoma (AC) of the lung increased much more rapidly than that of squamous cell carcinoma (SCC) in men and women. During this time period, filter cigarettes with substantially reduced "tar" and nicotine yields in the smoke came to dominate the market. METHODS: The risk of SCC and AC in lifelong smokers of filter cigarettes relative to lifelong nonfilter cigarette smokers was assessed in a case-control study performed between 1977 and 1995 with 2292 lung carcinoma patients and 1343 hospital controls who were current smokers. RESULTS: Odds ratios (OR) for SCC in male and female subjects who had smoked filter cigarettes exclusively during their lives were slightly reduced relative to lifetime nonfilter cigarette smokers in men (OR = 0.8; 95% confidence interval [CI], 0.5-1.2), and significantly reduced in women (OR = 0.4; 95% CI, 0.2-0.8). No reduction in risk was observed for AC of the lung in men or women. CONCLUSIONS: Evidence that the increasing predominance of AC over SCC may be due in part to the reduced risk of SCC (but not AC) associated with lifelong filter cigarette smoking is strongest in women; for men, further studies that include larger numbers of lifetime filter smokers are needed to confirm this finding. A lack of protection against AC from low yield filter cigarettes may result from smokers' "compensating" with deeper and more frequent inhalation, thereby increasing delivery of carcinogens to the peripheral lung. The smoke of modern cigarettes also contains higher concentrations of nitrosamines that primarily produce AC.