Artificial sweetener use and bladder cancer: a case-control study.

In a case-control study of 302 male and 65 female bladder cancer patients and an equal number of other patients matched to them in age, sex, hospital, and hospital-room status, no association was found between use of artificial sweeteners or diet beverages and bladder cancer. No dose-response was observed with respect to quantity or duration of use of the two combined. No evidence was found to suggest that artificial sweeteners or diet beverages promote the tumorigenic effect of tobacco smoking. Artificial sweetener and diet beverage use strongly reflected socioeconomic status among controls with various diagnoses.

Ignoring puff counts: another shortcoming of the Federal Trade Commission cigarette testing programme.

OBJECTIVES: To examine reasons behind the failure of the Federal Trade Commission (FTC) to preserve puff count information from standard cigarette testing and to elucidate the importance of puff count to overall tar yields. METHODS: We reviewed industry documents on origins of the FTC test and datasets provided by the Tobacco Institute Testing Laboratory to the tobacco industry and FTC for reporting purposes. RESULTS: The majority of the tobacco industry argued for "dual reporting" of tar yields-both per cigarette and per puff. Despite a request from the Tobacco Institute in 1967 that puff count information be preserved, documents and recent communications with the FTC indicate that puff number data have not been maintained by the government. In contrast, for the cigarette industry, puff count data are a fundamental and routine part of testing and important to cigarette design. A sample of puff counts for cigarettes tested in 1996 (n = 471) shows that on average 100 mm cigarettes have 18% more puffs taken on them than do 85 mm cigarettes in standard tests (7.66 vs 9.03; p<0.01). The 10th percentile puff count is 6.8 and the 90th percentile is 8.8 for king size; the 10th percentile puff count is 8.2 and the 90th percentile is 10.0 for 100 mm cigarettes, indicating that puff counts can vary substantially among brands. CONCLUSIONS: The FTC has failed to seek or preserve puff count information that the industry finds important. Any standard test of tar and nicotine yields should at minimum preserve puff count information.

Impact of long-term filter cigarette usage on lung and larynx cancer risk: a case-control study.

A case-control study was conducted among 1.034 white male and female hospital patients with histologically proved lung cancer (Kreyberg type l) or larynx cancer. After adjustment for duration of the smoking habit, inhalation, and butt length, relative risks of developing lung or larynx cancer were consistently lower among long-term smokers of filter cigarettes than among smokers of nonfilter cigarettes, irrespective of quantity smoked. Relative risks in all groups declined with increased years of smoking cessation. The observed risk reduction among current smokers of filter cigarettes was consistent with that expected, considering that these persons had smoked the older high-tar nonfilter cigarettes for a large proportion of their lives.

Smoking habits and tar levels in a new American Cancer Society prospective study of 1.2 million men and women.

In 1982 the American Cancer Society (ACS) enrolled over 1.2 million American men and women in a prospective mortality study of cancer and other causes in relation to environmental and life-style factors. Biennial follow-up is planned through 1988. At the time of enrollment, 23.6% of the men and 20.0% of the women were current smokers of cigarettes. Compared with a similar ACS study of 1 million subjects enrolled 23 years earlier, among men the proportion of current smokers was halved and that of ex-smokers doubled, while among women the proportion of ever-smokers increased by 10% and that of ex-smokers quadrupled. Most smokers of filter cigarettes had smoked nonfiltered cigarettes earlier in life. The median year for switching to filters was 1964, the year of the first Surgeon General's report. More than one-third of male smokers' and one-half of female smokers' current brands had tar yields below 12 mg; less than 9% of male smokers' and 4% of female smokers' current brands had tar yields of 20.2 mg or more (nonfilters). The study population differed in many respects from the general U.S. population; the study population had, for example, a much higher average educational level. Nevertheless, distributions of smoking habits changed a few percentage points after adjustment to the educational level of the general population.

Doses of nicotine and lung carcinogens delivered to cigarette smokers.

BACKGROUND: Cigarette smoke yields of tar and nicotine obtained under the Federal Trade Commission (FTC)-specified machine-smoking protocol (35-mL puff volume drawn for 2 seconds once per minute) may not accurately reflect the delivery of toxins and carcinogens to the smoker. We conducted this study to obtain more realistic estimates of exposure to components of cigarette smoke that affect lung cancer risk. METHODS: We used a pressure transducer system to evaluate puffing characteristics for 133 smokers of cigarettes rated by the FTC at 1.2 mg of nicotine or less (56 smokers of low-yield cigarettes [

Smoking and lung cancer in women: findings in a prospective study.

Lung cancer rates in relation to smoking habits were studied in a cohort of 619,225 women traced over a 4-yr period (1982 to 1986). A total of 1,006 lung cancer deaths was recorded. The standardized mortality ratio (SMR) for women smokers was 12.7 for current smokers and 4.8 for exsmokers. For those women without a history of chronic diseases, the SMR rose to 17.6 for current smokers. The SMRs rose with the number of cigarettes smoked per day to 22.0 for women who smoked 31 or more per day. SMRs also increased with depth of inhalation; this increase was independent of the number smoked per day. SMRs also increased by duration of smoking and decreased with cessation of smoking. Mortality ratios for lung cancer in women ranged from about 2 to 1 to 3 to 1 in studies carried out in the 1950s and 1960s. As women have begun to smoke earlier in life, smoke more cigarettes a day, and inhale more deeply, we are now observing much higher SMRs in women with lung cancer, similar in magnitude to those seen in men in the earlier studies.

Comparative epidemiology of tobacco-related cancers.

In a retrospective study, interviews were obtained with 3,716 patients with histologically proven cancer of the lung (Kreyberg types I and II), mouth, larynx, esophagus, or bladder and with over 18,000 controls. For each of these cancers, the relative risk of both male and female present smokers increased with the quantity smoked and the duration of the habit. The strongest increase occurred for cancer of the lung and larynx, and the least increase occurred for cancer of the esophagus and bladder. For exsmokers the risk decreased with years of cessation. The risk for mouth cancer of pipe and cigar smokers who inhaled much less than cigarette smokers was less than that of the latter and increased with the quantity smoked. The risk of mouth, larynx, and esophagus cancer among smokers increased with the quantity of alcohol consumed. Greater smoking habits and lesser cessation rates were noted among lower socioeconomic groups, suggesting that these groups will bear an ever increasing proportion of the burden of tobacco-related cancer.

An extremely compensatible cigarette by design: documentary evidence on industry awareness and reactions to the Barclay filter design cheating the tar testing system.

BACKGROUND: The Barclay cigarette (Brown & Williamson) was introduced in 1980 in the USA in the most expensive launch in history. In the USA and around the world, Barclay was later determined to have a grooved filter design that was compromised by human smokers in the normal act of smoking, but that was measured as ultra-low tar using the standard tar testing protocol. OBJECTIVES: To evaluate whether Brown & Williamson knew of the compensatability of Barclay during the design process and before it was released; to evaluate initial responses of competing tobacco companies to Barclay, before complaints were made to the Federal Trade Commission in 1981. METHODS: Internet databases of industry documents (Tobacco Documents Online, Legacy Tobacco Documents Library, Brown & Williamson Litigation discovery website, Guildford and major company websites) were searched using key words, key dates, and targeted searches. Documents related specifically to the development, evaluation and release of the Barclay cigarette and related to the responses by competing tobacco companies were examined. RESULTS: Documents indicate the manufacturer was aware of Barclay design problems and was planning, before release, to respond to criticism. Competing companies quickly detected the filter groove stratagem and considered developing their own similar filter, but eventually backed off. CONCLUSION: The design problems with Barclay were readily understood by cigarette manufacturers, including the maker of Barclay, before official governmental evaluations occurred. Testing involving measured exposures to human smokers may in the end be crucial to identifying problems with novel cigarette designs.

Smoking and pancreatic cancer in men and women.

Most studies of smoking and pancreatic cancer have used male subjects or combined men and women together in statistical analyses. There is little information on the relative risk of smoking and pancreatic cancer in women. Because of the high case-fatality rate, many of these studies were also based on information gathered from proxy respondents, in which smoking habits may not be recalled with certainty. A hospital-based study of 484 male and female patients with pancreatic cancer and 954 control subjects was conducted based on direct interviews of incident cases. Compared to never smokers, the odds ratio (OR) for current cigarette smokers was 1.6 [95% confidence interval (CI), 1.1-2.4] for men and 2.3 (95% CI, 1.4-3.5) for women. In women, but not in men, there was a trend in the ORs with years of daily cigarette consumption (P < 0.01). Filter cigarettes offered no protective advantage compared to nonfilter cigarettes. Among men, the OR was 2.1 (95% CI, 1.2-3.8) for pipe/ cigar smokers and 3.6 (95% CI, 1.0-12.8) for tobacco chewers. Tobacco smoke causes pancreatic cancer when inhaled into the lungs. Tobacco juice may also cause pancreatic cancer when ingested or absorbed through the oral cavity. These data suggest that smoking is a cause of pancreatic cancer in women and that the risks for female smokers are comparable to male smokers. Nevertheless, the causes of most pancreatic cancers are unknown.

Cigarette smoking and large cell carcinoma of the lung.

Large cell carcinoma is the fourth most common histological type of lung cancer in the United States. Cigarette smoking causes large cell lung cancer, but it is uncertain whether the effect varies with the amount and duration of smoking. This uncertainty stems from ambiguity in the histopathological classification of large cell cancer, especially before 1971, and the relatively infrequent occurrence of large cell cancer in epidemiological studies. The present case-control investigation demonstrates that the risk of large cell cancer increases with both the frequency and number of years of cigarette smoking. The odds ratio associated with smoking two or more packs/day was 37.0 (95% confidence interval, 16.4-83.2) in men and 72.9 (35.4-150.2) in women. It is concluded that cigarette smoking is the predominant cause of large cell lung cancer.

Breast cancer risk in relation to adipose concentrations of organochlorine pesticides and polychlorinated biphenyls in Long Island, New York.

To assess a possible etiological role of organochlorine compounds in breast cancer development on Long Island, a high-risk region of New York State, concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs) were measured in the adipose tissue of 232 women with breast cancer and 323 hospital controls admitted to surgery for benign breast disease or non-breast-related conditions. Seven pesticide residues and 14 PCB congeners were assayed via a supercritical fluid extraction method followed by gas chromatography with electron capture detection. After adjustment for age and body mass index, which were strongly correlated with organochlorine levels, adipose concentrations of 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, and total polychlorinated biphenyls (PCBs) did not differ significantly between cases and controls. The relative abundance of individual pesticide species and PCB congeners was similar in cases and controls. Odds ratios adjusted for age, BMI, hospital, and race gave no evidence of a dose-response for 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, or total PCBs, whether stratified by estrogen receptor status or not. Breast cancer risk among Long Island residents was not elevated compared with residents of the adjacent New York City borough of Queens. We did not confirm a previously reported association between breast cancer risk and levels of PCB congener 118 (2,3',4,4',5-pentachlorobiphenyl), nor did we observe an association with the most abundant congener 153 (2,2',4,4',5,5'-hexachlorobiphenyl), a strong inducer of phase I enzymes that was reported recently to have estrogenic properties. Only PCB congener 183 (2,2',3,4,4',5',6-heptachlorobiphenyl), which is also an inducer, was significantly associated with risk, with an adjusted odds ratio of 2.0 (95% confidence interval, 1.2-3.4) in women with adipose levels >5.67 ng/g; the biological importance of this observation is unclear without confirmation in additional studies. Although neither the present nor other studies have provided convincing evidence of an association between body burden of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane and PCBs with cancer of the breast, these compounds are rated as "possible" and "probable" human carcinogens, respectively, by the International Agency for Research on Cancer. Investigations of associations with cancer at other sites should be carried out.

Role of polymorphisms in codons 143 and 160 of the O6-alkylguanine DNA alkyltransferase gene in lung cancer risk.

O6-Alkylguanine DNA alkyltransferase (AGT) plays an important role in the repair of alkylating agent-induced DNA damage and protection from the carcinogenic effects of environmental agents. To examine the importance of the AGT codon 143 and codon 160 polymorphisms in risk for lung cancer and to assess the prevalence of these polymorphisms in different racial groups, we performed genotype analysis of lung cancer patients and matched controls. The prevalence of the AGT143Val allele in controls was 0.07 in Caucasians and 0.03 in African Americans. The AGT143Val allele was not detected in an unmatched Asian control cohort. The prevalence of the AGT160Arg variant allele was 0.01 in Caucasians, 0.02 in African Americans, and 0.03 in Asians. A marginally significant association was observed between the AGT codon 143 (isoleucine/valine) genotype and risk for lung cancer (odds ratio = 2.1; 95% confidence interval = 1.01-4.7). The prevalence of the AGT160Arg variant allele was similar in lung cancer cases versus matched controls. These results suggest that the AGT codon 143 polymorphism may play an important role in risk for lung cancer.

Relative abundance of organochlorine pesticides and polychlorinated biphenyls in adipose tissue and serum of women in Long Island, New York.

Some organochlorine pesticides (OCPs) and PCBs are under investigation as possible risk factors for breast cancer because of their estrogenic properties and widespread presence in the environment. It is important to know whether adipose tissue used by some investigators and serum assays used by others can provide comparable information on body burden. Concentrations of seven OCPs or their breakdown products as well as 14 PCB congeners were measured in the adipose tissue and serum of 293 women enrolled as controls in a case-control study of environmental factors for breast cancer in Long Island, New York, a high-risk region. Adipose OCP/PCB levels were measured using a supercritical fluid extraction method developed by the authors. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene (p,p'-DDE) was detected in all adipose and serum samples; two chlordane derivatives, beta-hexachlorocyclohexane (a lindane isomer) and hexachlorobenzene, were detected in at least 92% of adipose samples. The di-ortho hexachlorinated PCB congeners 2,4,5,2',4',5'-hexachlorobiphenyl and 2,3,4,2',4',5'-hexachlorobiphenyl were detected in all adipose and over 98% of serum samples. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene comprised 77% of total pesticide residues in adipose and 71% in serum. 2,4,5,2',4',5'-Hexachlorobiphenyl comprised 24% of adipose and 21% of serum PCBs. The relative concentration patterns of the 14 PCB congeners were similar to those reported in other human studies and were also typical of patterns reported in environmental samples from various biota, including mammals and birds, but differed substantially from patterns reported in occupationally exposed workers. All adipose-serum correlations for pesticides and most PCBs were statistically significant. Either serum or adipose OCP/PCB levels of a variety of environmental organochlorine compounds may serve as useful biomarkers of body burden.

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.

Handheld cellular telephones and risk of acoustic neuroma.

The hypothesis that intracranial energy deposition from handheld cellular telephones causes acoustic neuroma was tested in an epidemiologic study of 90 patients and 86 control subjects. The relative risk was 0.9 (p = 0.07) and did not vary significantly by the frequency, duration, and lifetime hours of use. In patients who used cellular telephones, the tumor occurred more often on the contralateral than ipsilateral side of the head. Further efforts should focus on potentially longer induction periods.

The epidemiology of left-handedness in a hospital population.

PURPOSE: We evaluated the association between left-handedness (LH) and age, education, cigarette smoking, alcohol consumption, and disease status in a case-control study of 8801 hospitalized patients with cancer and those with other conditions. METHODS: Subjects were interviewed in person using a structured questionnaire that contained detailed sections of lifestyle behaviors. RESULTS: The overall prevalences of LH were 7.6% among men and 6.5% among women. Among both sexes LH declined with increasing age (P < 0.05). After adjustment for age, the following associations were observed. Men had a higher risk of LH than women. The prevalence of LH was lower in ever-married subjects compared with never-married subjects (odds ratio [OR] for men, 0.7; 95% confidence intervals [CI], 0.5-0.9; for women, OR, 0.5; 95% CI, 0.3-0.9). Among men, the prevalence of LH was not associated with race, years of education, smoking status, or levels of alcohol consumption. The risk of LH was elevated in men diagnosed with fractures as compared with all other male patients (OR, 2.4; 95% CI, 1.3-6.7). Among women, LH was not associated with race, smoking, or hormonal and reproductive factors, but LH was more common among female high-school and college graduates and among self-reported alcoholics. The odds ratio of LH was significantly lower in women with breast cancer (OR, 0.3; 95% CI, 0.1-0.7). CONCLUSIONS: The increased risk of serious injuries in LH is not a result of higher alcohol use. Handedness might be an important factor in the safe use of industrial equipment.

Exposure to Agent Orange and occurrence of soft-tissue sarcomas or non-Hodgkin lymphomas: an ongoing study in Vietnam.

Agent Orange was the most common herbicide used in the Second Indochina War in the course of military operations in the former South Vietnam. Agent Orange is contaminated by the carcinogen 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in mean concentrations of 2 mg/kg. After much dispute of a causal association between exposure to herbicides containing TCDD and occurrence of soft-tissue sarcoma and non-Hodgkin lymphoma, two simultaneous case-control studies were set up in Vietnam to examine possible relationships. Subject recruitment is ongoing, with target numbers of 150 cases of soft-tissue sarcoma and 150 cases of non-Hodgkin lymphoma and diagnoses at the Cancer Center at Ho Chi Minh City, Vietnam. Two hospital controls are matched to each case. As in other studies of cancer in persons occupationally or otherwise exposed to herbicides and their contaminants, evaluation of past exposure of the recruited subjects is among the most complicated issues. Because accurate records are usually unavailable, surrogate measures of likely exposure are often calculated. As a first approach in our studies we used the Stellman and Stellman exposure index. The index is based on matching subjects' history of residence and the information on times and locations of Agent Orange spraying recorded on HERBS tape by the U.S. Army and taking into account the distance from the spraying as well as environmental and biologic half-life of TCDD. The exposure index is calculated in two centers, New York and Hanoi, with slightly different assumptions. In addition, samples of body tissues from the subjects (20 ml blood, 2 g adipose tissue, and tumor sections in paraffin blocks) are taken and stored. Their future analysis will provide additional source of exposure assessment. Strengths and weaknesses of both exposure measures are discussed in this paper.

Smoking prevalence in neighborhood and hospital controls: implications for hospital-based case-control studies.

It is widely believed that the prevalence of smoking among hospital patients is greater than that of the general population because many conditions for which patients are hospitalized are caused by or associated with smoking, and that this increased prevalence may bias results of case-control studies of tobacco-related diseases. For this reason, many authors have suggested excluding from the control series patients hospitalized for tobacco-related illnesses. The present study investigated potential selection bias for hospital compared to neighborhood controls in studying tobacco-related diseases. The 709 cases from six U.S. cities had tobacco-related cancers or myocardial infarction. They were individually matched to one hospital control and to one neighbor. After excluding patients with tobacco-related diseases, hospital controls were less often current smokers and more often former smokers than neighborhood controls. Among male ever smokers, hospital controls tended to smoke more cigarettes per day than neighborhood controls. Compared with the U.S. population, there was an overrepresentation of smokers in neighborhood controls rather than an under-representation of smokers in hospital controls. Relative risk estimates varied according to type of control. Choosing between hospital and neighborhood controls in case-control studies should be dictated by criteria related to the study hypothesis, participation, or cost. In particular, exclusion of hospital controls with diseases known to be tobacco-related seems to be a successful strategy for reducing selection bias.

Proportional mortality ratios among Korean immigrants to New York City, 1986-1990.

BACKGROUND: About 13,000 people immigrated to New York City from the Republic of Korea between 1986 and 1990, creating an important ethnic minority. METHODS: Using US-born Whites as a reference, age-adjusted proportional mortality ratios were computed for 314 men and 248 women of Korean ancestry born abroad who died in New York City in 1986-90. RESULTS: Males had a significant excess of viral hepatitis, cancer, stroke, and external causes: accidents, suicide, and homicide. They had significantly reduced proportional rates of AIDS and heart disease. Mortality patterns were similar for Korean women, who had significantly increased proportional rates of stroke and accidents, and reduced heart disease. Stomach and liver cancers were significantly elevated in both sexes, while female breast cancer was low. There were two male and one female tuberculosis deaths (4 to 7 fold increase), and one Korean woman died of childbirth complications (59-fold increase). CONCLUSIONS: Except for violent deaths, these observations resemble known mortality patterns in Korea.