Soft tissue sarcoma and tobacco use: data from a prospective cohort study of United States veterans

A report of an increased risk of soft tissue sarcoma (STS) among users of smokeless tobacco led us to evaluate this association and the role of other types of tobacco in a prospective cohort mortality-study of United States veterans. A total of 248,046 veterans provided tobacco-use histories on a mail questionnaire in 1954 or 1957. Data on subsequent tobacco use were not collected. By 1980, 119 deaths from STS had occurred among the cohort members. Veterans who had ever chewed tobacco or used snuff had a nonsignificant 40 percent excess of STS (95 percent confidence interval [CI]=0.8–2.6; 21 deaths) in comparison with veterans who had never used any tobacco products. Risk was limited to former users (relative risk [RR]=1.5) with no excess seen among current users (RR=0.9). Frequent former users had higher risk (RR=1.9) than infrequent users (RR=1.3). Risk was slightly higher in persons who started using smokeless tobacco at younger ages, but did not increase with duration of use or with late age at cessation of use. Most veterans who used chewing tobacco or snuff also used some other form of tobacco. No STS deaths occurred among the 2,308 veterans who used smokeless tobacco only. An unexpected finding of the study was the significant excess of STS deaths among cigarette smokers (RR=1.8, CI=1.1–2.9). Risk was higher among ex-smokers (RR=2.2) than among current smokers (RR=1.5) and was not related to number of cigarettes per day, age started smoking, duration, or pack-years. Pipe and cigar smokers also experienced a nonsignificant excess risk (RR=1.6). The study findings may have been affected by limitations in the histories of tobacco use, the quality of death certificate data on STS, and the small number of STS deaths, particularly among users of smokeless tobacco.Drs Zahm and heineman are with the Occupational Studies Section, Environmental Epidemiology Branch, Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD, USA. Dr Vaught is with Westat, Inc., Rockville, MD. USA. Address correspondence to Dr Zahm, Occupational Studies Section, National Cancer Institute, Executive Plaza North, Room 418, Rockville, MD 20892, USA.     

Cigarette smoking and liver cancer among US veterans

The relationship of tobacco use with risk of primary liver cancer was investigated using data from a 26-year mortality follow-up of nearly 250,000 US veterans, mostly from World War I. Significantly increased risks for liver cancer (289 deaths) were associated with most forms of tobacco use, including pipe and cigar smoking. Elevated relative tisks (RRs) were seen for current cigarette smokers (RR=2.4; 95 percent confidence interval [CI] 1.6–3.5) and former cigarette smokers (RR=1.9, 1.2–2.9). A strong dose-response relationship (P<0.001) was found for cigarette smoking, with smokers of 40 or more cigarettes per day having almost a fourfold risk (RR=3.8, 1.9–8.0). Risks were also found to increase significantly with years of cigarette use and with earlier age at the start of cigarette smoking. These results are consistent with those of other cohort and case-control studies, suggesting that cigarette smoking may be related to the risk of liver cancer.All authors are in the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute. Address correspondence to Dr Hsing at Executive Plaza North, Room 415, Bethesda, MD 20892, USA.     

A prospective study of cigarette tar yield and lung cancer

We examined the relationship of cigarette tar yield and other cigarette-usage characteristics in current smokers to the incidence of lung cancer in a study population of 79,946 Kaiser Permanente Medical Care Program members, aged 30–89 years, who completed a detailed, self-administered, smoking-habit questionnaire during the years 1979 through 1985. Mean length of follow-up was 5.6 years. There were 302 incident lung cancers, of which 89 percent occurred in current or former smokers. The tar yield of the current cigarette brand was unassociated with lung cancer incidence (relative risk [RR]=1.02 per 1 mg tar-yield in men, 95 percent confidence interval [CI]=0.98–1.05; RR=0.99, CI=0.96–1.03 in women). However, in long-term (>20 years) smokers, the risk of lung cancer was decreased in women who had smoked filtered cigarettes for 20 or more years relative to lifelong smokers of unfiltered cigarettes (RR=0.36, CI=0.18–0.75), but not in men who had smoked filtered cigarettes for 20 or more years (RR=1.04, CI=0.58–1.87).Authors are with the Division of Research, Kaiser Permanente Medical Care Program, 3451 Piedmont Avenue, Oakland, CA 94611, USA. Address correspondence to Dr Sidney. This study was funded by grants R01 CA 36074 and R35 CA 49761 from the US National Cancer Institute.     

Tobacco use and prostate cancer in Blacks and Whites in the United States

Prostate cancer occurs more frequently in Blacks than Whites in the United States. A population-based case-control study which investigated the association between tobacco use and prostate cancer risk was carried out among 981 pathologically confirmed cases (479 Blacks, 502 Whites) of prostate cancer, diagnosed between 1 August 1986 and 30 April 1989, and 1,315 controls (594 Blacks, 721 Whites). Study subjects, aged 40 to 79 years, resided in Atlanta (GA), Detroit (MI), and 10 counties in New Jersey, geographic areas covered by three, population-based, cancer registries. No excesses in risk for prostate cancer were seen for former cigarette smokers, in Blacks (odds ratio [OR]=1.1, 95 percent confidence interval [CI]=0.7–1.5) and in Whites (OR=1.2, CI=0.9–1.6), or for current cigarette smokers, in Blacks (OR=1.0, CI=0.7–1.4) and in Whites (OR=1.2, CI=0.8–1.7). Increases in risk were noted for smokers of 40 or more cigarettes per day, among former (OR=1.4, CI=1.0–1.5) and current (OR=1.5, CI=1.0–2.4) smokers. Duration of cigarette use and cumulative amount of cigarette use (pack-years) were not associated with prostate cancer risk for Blacks or Whites. By age, only the youngest subjects, aged 40 to 59 years, showed excess risk associated with current (OR=1.5, CI=1.0–2.3) and former (OR=1.7, CI=1.1–2.6) use of cigarettes, but there were no consistent patterns in this group according to amount or duration of smoking. Risks also were not elevated for former or current users of pipes, cigars, or chewing tobacco, but the risk associated with current snuff use was OR=5.5 (CI=1.2–26.2). This subgroup finding may have been due to chance. The results of the present study may be consistent with a small excess risk for prostate cancer associated with tobacco use, but the lack of consistent findings in population subgroups and the lack of a clear dose-response relationship argue more strongly that no causal association exists. The data do not indicate that the Black-White difference in prostate cancer risk is related to tobacco use.This research was performed under contracts: NO1-CP-51090, NO1-CN-0522, NO1-CP-51089, NO1-CN-31022, NO1-CP-51092, and NO1-CN-5227.     

Are the known bladder cancer risk-factors associated with more advanced bladder cancer?

Risk factors for superficial and invasive bladder cancer were examined in a case-control study of 470 cases Identified in 1967–68 in the Brockton and Boston Standard Metropolitan Areas (MA, United States) and of 500 population-based controls. Histologic specimens were reviewed and classified as superficial or invasive, following a standardized protocol. The tobacco-associated risk for superficial bladder cancer was odds ratio (OR)=2.6 (95 percent confidence interval [CI]=1.7–4.1) and the risk for invasive bladder cancer was OR=1.7 (CI=1.1–2.5). For subjects less than 60 years of age, the risks were greater for invasive tumors (OR=4.3, CI=1.2–15) than for superficial tumors (OR=0, CI=0.9–4.2), but this pattern for tobacco use was not found in older subjects. A strong trend of increased risk with increased amount of cigarettes smoked was shown only for invasive bladder tumors. No clear pattern of excess risk for invasive bladder tumors was seen for age at first use and years since last use of tobacco. The risk associated with occupational exposure to aromatic amine bladder carcinogens was OR=1.7 (CI=0.8–3.3) for superficial and OR=1.5 (CI=0.8–3.0) for invasive bladder cancer. For subjects less than 60 years of age, the risks were greater for invasive (OR=12.0, CI=2.1–65) than for superficial tumors (OR=4.3, CI=0.8–24), but this pattern for occupational exposure was not found in older subjects. Risk by age at first exposure to occupational aromaticamine, bladder carcinogens was similar for superficial and invasive tumors. Overall, there was no association between known bladder-cancer risk-factors and more advanced bladder cancer. The relative risk associated with cigarette smoking and occupational exposure to aromatic amines was higher for invasive than superficial cancer only for men less than 60 years of age.Drs Hayes and Zahm are with the Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. Authors are affiliated also with the Lucille P. Markey Cancer Center, Lexington, KN, USA (Dr Friedell) and the Department of Epidemiology, University of Alabama, Birmingham, AL, USA (Dr Cole). Address correspondence to Dr Hayes, Environmental Epidemiology Branch, National Cancer Institute, EPN 418, Bethesda, MD 20892, USA.     

Occupational risk factors for lung cancer among nonsmoking women: a case-control study in Missouri (United States)

Occupationally related risk of lung cancer among women and among nonsmokers has not been widely studied. A recently conducted population-based, case-control study in Missouri (United States) provided the opportunity to evaluate risk of lung cancer associated with several occupational factors. Incident cases (n=429) were identified through the Missouri Cancer Registry for the period 1986 through 1991, and included 294 lifetime nonsmokers and 135 ex-smokers who had stopped at least 15 years prior to diagnosis or had smoked for less than one pack-year. Controls (n=1,021) were selected through driver's license and Medicare files. Risk was elevated among women exposed to asbestos (ever: odds ratio [OR]=3.5, 95 percent confidence interval [CI]=1.2–10.0; >9 yrs: OR=4.6, CI=1.1–19.2) and pesticides (ever: OR=2.4, CI=1.1–5.6; >17.5 yrs: OR=2.4, CI=0.8–7.0). Risk also was elevated among dry cleaning workers (ever: OR=1.8, CI=1.1–3.0; >1.125 yrs: OR=2.9, CI=1.5–5.4). Occupational risks for lung cancer among women merit further study.Drs Brownson and Chang are with the Missouri Department of Health, Columbia, MO, USA. Dr Alavanja is with the Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD, USA. Dr Chang directs the Missouri Cancer Registry with the Missouri Department of Health. Address correspondence to Dr Brownson, Division of Chronic Disease Prevention and Health Promotion, Missouri Department of Health, 201 Business Loop 70 West, Columbia, MO 65203, USA. This study was supported in part by US National Cancer Institute contracts NO1-CP7-1096-01 and NO1-CP7-1096-02.     

Oral contraceptives and primary liver cancer among young women

The association of oral contraceptive use with liver cancer was examined in a study of 76 deaths from primary liver cancer, 22 deaths from cancer of the intrahepatic bile ducts, and 629 controls among women aged 25 to 49 years. The subjects in the study are from the 1986 National Mortality Followback Survey, which included a questionnaire sent or administered to the next-of-kin of almost 20,000 deceased individuals in the United States. Information on a number of lifestyle factors was collected, including questions on oral contraceptive use. Increased risks of primary liver cancer were found for ever-users (odds ratio [OR]=1.6, 95 percent confidence interval [CI]=0.9–2.6), and for long-term (10 years) users (OR=2.0, CI=0.8–4.8) of oral contraceptives. When the analysis was restricted to subjects whose spouse or parent was the respondent, more pronounced risks were seen for ever-users (OR=2.7, CI=1.4–5.3) and long-term users (OR=4.8, CI=1.7–14.0). No clear excess risk was found for cancer of the intrahepatic bile ducts. This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives.Authors are with the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, with the exception of Mr Co-Chion who is at Westat Inc., Rockville, MD, USA. Address reprint requests to Dr Hsing at the National Cancer Institute, Executive Plaza North, Room 415, Bethesda, MD 20892, USA.     

Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark

Polymyositis and dermatomyositis (PM/DM) have been associated with cancer, although the long-term risks are poorly understood. To evaluate the risk of cancer by time periods subsequent to PM/DM diagnosis, a cohort of 539 patients hospitalized with PM/DM in Denmark between 1977 and 1989 was identified from the Danish Central Hospital Discharge Register. Cancer incidence among cohort members was ascertained by linkage to the Danish Cancer Registry using a unique personal-identification number. The overall cancer risk was elevated significantly among patients with DM (standardized incidence ratio [SIR]=3.8, 95 percent confidence interval [CI]=2.6–5.4) and to a lesser extent PM (SIR=1.7, CI=1.1–2.4). Significant excesses were observed for cancers of lung, ovary, and lymphatic and hematopoietic system. However, the excess cancer incidence declined steadily with increasing years since initial diagnosis of PM/DM. The cancer risk was increased about sixfold (SIR=5.9, CI=3.8–8.7) during the first year, but was lower during the second year (SIR=2.5, CI=1.1–4.8), with no significant excesses in subsequent years of follow-up. These findings confirm that PM/DM may occur as a paraneoplastic syndrome that calls for steps aimed at early cancer detection and treatment. Among long-term survivors of PM/DM, however, there is little evidence to warrant extensive preventive and screening measures beyond those recommended for the general population.Drs Chow, McLaughlin, and Fraumeni, and Ms Gridley are with the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, MD, USA. Dr McLaughlin is currently with the International Epidemiology Institute, Rockville, MD. Ms Mellemkjær and Dr Olsen are with the Division for Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. Address correspondence to Dr Chow, National Cancer Institute 6130 Executive Blvd, EPN/415, Rockville, MD 20852, USA.     

Incidence of childhood cancer in twins

The incidence of childhood cancer in twins was evaluated by linking a roster of 30,925 twins born in Connecticut (United States) between 1930 and 1969 with the Connecticut Tumor Registry. Cancer, exclusive of nonmelanoma skin cancer, was identified in 19 females and 12 males under 15 years of age. The incidence rate among twins was 7.9 cancers per 100,000 person-years (PY) overall, and 9.7 and 6.1 per 100,000 PYs for females and males, respectively. Four of 13 leukemias occurred in two female twin pairs, representing concordance rates of 18 percent overall and 29 percent for like-sex pairs, which are somewhat higher than values reported previously. The number of cancers expected was computed on the assumption that twins experienced the same sex-, age-, and calendar time-specific cancer rates as recorded for all Connecticut-born children. Because active follow-up of individuals was not conducted, an adjustment to person-years of observation was made to account for childhood mortality, including the high perinatal mortality characteristie of twins. Childhood cancer was 30 percent less frequent than expected (standardized incidence ratio [SIR]=0.7; 95 percent confidence interval [CI]=0.5–0.9), a deficit that is marginally greater than those found in previous studies. Both leukemia (SIR=0.8; CI=0.4–1.4), and all other cancers combined (SIR=0.6; CI=0.3–0.9) occurred less often than expected. The deficit was greater among males (SIR=0.5; CI=0.2–0.8) than among females (SIR=0.9; CI=0.5–1.4) and was especially pronounced among males younger than five years (SIR=0.2; CI=0.0–0.7). The data support the view that twins, particularly male twins, have a lower risk of childhood cancer than single-born children. Any added risk for twins associated with their greater frequency of exposure to prenatal X-rays appears to have been insufficient to offset an effect of twinning per se. Possible explanations for this finding include (i) the low birthweight distribution of twins, or (ii) selective early mortality of twin fetuses or neonates who would otherwise have developed a clinical cancer.Drs Inskip, Boice, Stone, and Fraumeni are with the Epidemiology and Biostatistics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Dr Harvey was in the Epidemiology and Biostatistics Program at the time of this research and is now with Sterling Drug, Malvern, PA, USA. Dr Matanoski is in the Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, USA. Dr Flannery is with the Connecticut Tumor Registry, Hartford, CT, USA. Address correspondence to Dr Inskip, Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 408, Rockville, MD 20852, USA. This study was supported in part by Contract N01-CPO-1047 with the National Cancer Institute, US Public Health Service.     

Eating frequency—a neglected risk factor for colon cancer?

Eating frequency was examined in relation to risk of cancer of the colon and rectum in a population-based case-control study conducted in Stockholm, Sweden in 1986–88. In the present analysis, 328 cases and 500 controls were included. The adjusted relative risk (RR) of colon cancer per daily eating occasion was 1.2 (95 percent confidence interval [CI]=1.1–1.4, adjusted for year of birth, sex, intake of energy, fat, protein, and fiber, browning of meat surface, physical activity, and body mass index). The corresponding RR for rectal cancer was 1.0 (CI=0.9–1.2). The frequency of eating snacks was related to risk of colon cancer (RR per snack = 1.6, CI=1.2–1.9), while the frequency of eating meals (breakfast, lunch, or dinner) was not (RR per meal = 0.8, CI=0.6–1.1). The results are consistent with findings in two other case-control studies in which eating frequency was found to be a risk factor for colon cancer.Dr Gerhardsson de Verdier is with the Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, and the Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, CA, USA. Dr Longnecker is with the Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, USA. Address correspondence to Dr Gerhardsson de Verdier at the Institute of Environmental Medicine, Department of Epidemiology, Box 60208, S-104 01, Stockholm, Sweden. The study was supported by two grants (2228-B86-013XA; 2228-B87-02XA) from the Swedish National Cancer Society. Dr Longnecker is the recipient of a Junior Faculty Research Award from the American Cancer Society.     

Familial occurrence of hematologic malignancies and other diseases in multiple myeloma: a case-control study

In a population-based case-control study in Sweden on multiple myeloma, the occurrence of different diseases in relatives, particularly hematologic malignancies and different types of cancer, was investigated. Through a questionnaire mailed to all living subjects, i.e. cases and controls, and to the next-of-kin for deceased subjects, information was obtained on malignant and certain other diseases among relatives. All malignant diseases reported among first-degree relatives were verified, if possible, through parochial authorities and the Swedish Cancer Register. In total, data from 239 cases with myeloma and 220 controls were analyzed. An increased risk was found for persons with first-degree relatives with hematologic malignancies (relative risk [RR]=2.36, 90 percent confidence interval [CI]=0.90–6.15), and also with multiple myeloma specifically (RR=5.64, CI=1.16–27.51). An increased risk also was seen if the close relatives had experienced another tumor disease (RR=1.21, CI=0.86–1.71). Particularly, occurrence of prostatic cancer (RR=3.11, CI=1.25–7.71) or brain tumor (RR=6.61, CI=1.42–30.67) in relatives increased the risk for multiple myeloma.Dr Eriksson in with the Department of Oncology, University Hospital, S-901-85 Umeå, Sweden. Dr Hållberg is with the Department of Statistics, Umeå University, Umeå, Sweden. Address correspondence to Dr Eriksson. This research was supported by grants from the Swedish Cancer Fund. (Project 2683-B90-02X.)     

Cigarette smoking and leukemia: results from the Lutheran Brotherhood Cohort Study

In a 20-year follow-up (1966–86) of 17,633 White males who described tobacco use in a mailed questionnaire sent in 1966, there were 74 deaths from leukemia (including 30 myeloid, 30 lymphatic, and 14 other and unspecified leukemia). Among men who ever smoked cigarettes, increased risks were observed for lymphatic (relative risk [RR]=2.7), and other and unspecified leukemia (RR=1.5); risks rose with increasing number of cigarettes smoked, although the dose-response relationship was statistically significant only for total leukemia. Mortality from myeloid leukemia was not elevated, except among those smoking over a pack of cigarettes per day. Results from this cohort support a relationship between cigarette smoking and leukemia. Further studies are needed to elucidate subtype associations with cigarette smoking.Drs Linet, McLaughlin, Hsing, Wacholder, and Blot are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Co-Chien is at Westat, Inc., Rockville, Maryland, USA, Dr Schuman is at the University of Minnesota, Minneapolis, Minnesota, USA. Dr Bjelke is with the Center for Epidemiologic Research, University of Bergen, Norway. Address correspondence to Dr Linet, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North Room 415B, Bethesda, MD 20892, USA.     

Reproductive factors,exogenous female hormones,and colorectal cancer by subsite

The associations between reproductive factors, exogenous hormones, and colorectal cancer were examined among female subjects in a population-based case-control study in Sweden. The study was performed in Stockholm in 1986–88, and included 299 cases and 276 controls. There was little evidence that age at first birth, number of months of breast feeding, age at menarche, or age at menopause influenced the risk of colon or rectal cancer. However, the results indicate that postmenopausal hormone-replacement therapy might reduce the risk of colorectal cancer (age-adjusted relative risk [RR]=0.4, 95 percent confidence interval [CI]=0.2–0.9). Compared with nulliparous women, women with at least four births were at reduced risk for colon cancer (RR=0.5, CI=0.2–1.2) but not rectal cancer (RR=1.0, CI=0.4–2.6). However, no trend across increasing parity was observed. Adjustments for diet, body mass, and physical activity had little influence on the results.The authors are with the Department of Preventive Medicine, University of Southern California School of Medicine. Dr Gerhardsson de Verdier is also in the Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. Address correspondence to Dr London, University of Southern California School of Medicine, Department of Preventive Medicine, PMB B306, 1420 San Pablo Street, Los Angeles, CA 90033, USA. The study was supported by two grants (2228-B86-013XA; 2228-B87-02XA) from the Swedish National Cancer Society.     

Prospective study of the association of alcohol with cancer of the upper aerodigestive tract and other sites

The association of alcohol consumption with cancers of the upper aerodigestive tract, hepato-biliary-pancreatic system, urogenital organs (except for prostate), and lymphohematopoietic tissue was evaluated in a prospective study of 6,701 American men of Japanese ancestry living in Hawaii. Compared with cancer-free subjects, subjects who subsequently developed cancers of the upper aerodigestive tract (oral-pharynx, esophagus, and larynx), liver, biliary tract, and lymphohematopoietic tissue consumed significantly larger amounts of total alcohol-mainly in the form of beer. Subjects who developed oral-pharyngeal and esophageal cancer also consumed larger amounts of wine and spirits. Because the upper aerodigestive tract cancers were associated positively with cigarette smoking, age-adjusted relative risks (RR) were calculated, based on joint exposure to cigarette smoking and heavy alcohol intake (30 ml/day) in this population. A markedly increased risk was observed among subjects who were both heavy alcohol drinkers and smokers (RR=17.3, 95 percent confidence interval [CI]=6.7–44.2), compared with subjects who did not smoke and did not drink heavily. The risk for these cancers also was increased among heavy alcohol drinkers who were nonsmokers (RR=8.6, CI=2.1–36.0).Dr Kato is currently with the Division of Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. Drs Nomura, Stemmermann, and Chyou are with the Japan-Hawaii Cancer Study, Kuakini Medical Center, Honolulu, HI. Address correspondence to Dr Nomura, Japan-Hawaii Cancer Study, Kuakini Medical Center, 347 N Kuakini St, Honolulu, HI 96817, USA. This work was supported in part by Grant RO1 CA 33644 from the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.     

Pesticide exposures and multiple myeloma in Iowa men

A population-based case-control study of 173 White men with multiple myeloma (MM) and 650 controls was conducted in Iowa (United States), an area with a large farming population, to evaluate the association between MM, agricultural risk factors, and exposure to individual pesticides. A slight nonsignificantly elevated risk for MM was seen among farmers (odds ratio [OR]=1.2, 95 percent confidence interval [CI]=0.8–1.7). Although slight excesses were observed, there were no significant associations between MM and handling either classes of pesticides or specific pesticides. Thus, this study found little evidence to suggest an association between risk of MM and farming or pesticides.Ms Brown and Dr Blair are with the Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD, USA. Dr Burmoistor is with the Department of Preventive Medicine, University of Iowa, Iowa City, IA, USA. Dr Everett is with the Department of Internal Medicine, Orlando Regional Medical Center, Orlando, FL, USA. Address correspondence to Ms Brown, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North, Room 415, Bethesda, MD, USA. This project was supported in part by a grant from the National Institute of Environmental Health Sciences (ES 03099).     

Environmental tobacco smoke and lung cancer mortality in the American Cancer Society's Cancer Prevention Study II

Environmental tobacco smoke (ETS) has been classified as a human lung carcinogen by the United States Environmental Protection Agency (EPA), based both on the chemical similarity of sidestream and mainstream smoke and on slightly higher lung cancer risk in never-smokers whose spouses smoke compared with those married to nonsmokers. We evaluated the relation between ETS and lung cancer prospectively in the US, among 114,286 female and 19,549 male never-smokers, married to smokers, compared with about 77,000 female and 77,000 male never-smokers whose spouses did not smoke. Multivariate analyses, based on 247 lung cancer deaths, controlled for age, race, diet, and occupation. Dose-response analyses were restricted to 92,222 women whose husbands provided complete information on cigarette smoking and date of marriage. Lung cancer death rates, adjusted for other factors, were 20 percent higher among women whose husbands ever smoked during the current marriage than among those married to never-smokers (relative risk [RR]=1.2, 95 percent confidence interval [CI]=0.8-1.6). For never-smoking men whose wives smoked, the RR was 1.1 (CI=0.6-1.8). Risk among women was similar or higher when the husband continued to smoke (RR=1.2, CI=0.8-1.8), or smoked 40 or more cigarettes per day (RR=1.9, CI=1.0-3.6), but did not increase with years of marriage to a smoker. Most CIs included the null. Although generally not statistically significant, these results agree with the EPA summary estimate that spousal smoking increases lung cancer risk by about 20 percent in never-smoking women. Even large prospective studies have limited statistical power to measure precisely the risk from ETS.     

Incomplete pregnancies and risk of ovarian cancer (Washington, United States)

Because of the reduced risk of ovarian cancer related to prior full-term pregnancies, we sought to determine whether there was any association with a history of one or more incomplete pregnancies. White female residents of three counties in Washington State (United States) diagnosed with ovarian cancer during 1986–88 (n=322), and a random sample of control women selected from these same counties (n=426), were interviewed regarding their pregnancy and childbearing histories. Among women who had given birth to at least one child, an additional incomplete pregnancy was not associated with the risk of ovarian cancer (relative risk [RR]=1.1, 95 percent confidence interval [CI]=0.8–1.6, adjusting for age, oral contraceptive use, and number of births). For those who had never given birth, a somewhat smaller proportion of cases had a history of incomplete pregnancy than controls (RR=0.8, CI=0.4–1.7). In an analysis restricted to ever-pregnant women, a prior induced or spontaneous abortion was not found to be associated with the incidence of ovarian tumors (RR=1.0, CI=0.6–1.7, and RR=1.3, CI=0.8–1.9, respectively). Other studies of the possible relation between incomplete pregnancies and ovarian cancer generally have observed either a weak negative association or no association at all. It is possible that if incomplete pregnancies do affect the risk of ovarian cancer, their impact might be too small to be identified reliably through epidemiologic studies.This research was supported in part by a grant from the US National Cancer Institute (R35 CA39779), and by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by Contract No. N01-CN-05230 from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center.     

Difficulty becoming pregnant and family history as interactive risk factors for postmenopausal breast cancer: the Iowa Women's Health Study

We recently provided data from a prospective cohort study of postmenopausal women which suggested that a first livebirth at age 30 or older (cf before age 20) was associated with a twofold increased risk of breast cancer in women without a family history, but a 5.8-fold higher risk in women with a positive family history. To address the question of whether these observations reflect difficulty becoming pregnant or maintaining a pregnancy, we performed additional analyses in which the outcome of each pregnancy was considered. During five years of follow-up, 620 incident cases of breast cancer were identified in the 37,105 women at risk. There was little evidence for an increased risk associated with a history of spontaneous abortion (relative risk [RR]=1.1; 95 percent confidence interval [CI]=0.9–1.4), nor was the risk higher among women who reported two or more spontaneous abortions in consecutive pregnancies (RR=1.0, CI=0.7–1.4). Although women who reported that they had tried unsuccessfully to become pregnant had only slightly and nonsignificantly elevated risks of breast cancer (RR=1.1, CI=0.9–1.3), a more pronounced and statistically significant association was noted in women with a positive family history (RR=2.0, CI=1.4–3.2). There was a strong inverse association between failure to become pregnant and parity (P<0.0001); nearly 50 percent of the nulliparous married women reported having tried and failed to become pregnant, whereas the frequency was only 6.8 percent among married women with five or more livebirths. Thus, difficulties in becoming pregnant may characterize a subset of women at increased risk of breast cancer, especially in the presence of a family history.The authors are with the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN, USA. Dr Sellers is also affiliated with the Institute of Human Genetics, University of Minnesota School of Medicine. Address correspondence to Dr Sellers, Division of Epidemiology, Suite 300, 1300 South Second Street, Minneapolis, MN 55454-1015. This publication was supported by a grant (RO1 CA39742) from the US National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.     

Cancer risk in patients with diabetes mellitus

Cancer incidence was ascertained in a population-based cohort of 51,008 patients in Uppsala, Sweden, who were given a discharge diagnosis of diabetes mellitus during 1965–83. Complete follow-up through 1984 with exclusion of the first year of observation showed that the observed number of cancers in females (1,294) was eight percent higher than expected (relative risk [RR]=1.1, 95 percent confidence interval =11.0–1.1), whereas in males the observed number (1,123) was close to the expected (RR=1.0, 0.9–1.1). Significantly increased risks of pancreatic (RR=1.4, 1.2–1.7), primary liver (RR=1.5, 1.2–1.7), and endometrial (RR=1.5, 1.2–1.8) cancers and a lower than expected number of prostatic cancers (RR=0.7, 0.7–09) were found in this cohort of diabetic patients. The excess risk of pancreatic cancer was similar in females and males and evident both during one through four years (RR=1.7, 1.4–2.1) and five through nine years (RR=1.3, 0.9–1.7) of follow-up, but not thereafter. A similar pattern was found for primary liver cancer, but the RRs were generally higher in males than in females.Drs Adami and Ekbom are with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden; Dr Ekbom is also in the Department of Surgery. Drs McLaughlin and Silverman are with the Biostatistics Branch, National Cancer Institute, Bethesda, Maryland, USA. Dr Berne is in the Department of Internal Medicine, University Hospital, Uppsala, Sweden. Mr Hacker is with Information Management Services, Silver Spring, Maryland, USA. Dr Persson is in the Department of Obstetrics and Gynaecology, University Hospital, Uppsala, Sweden. Address correspondence to Dr Adami, Cancer Epidemiology Unit, University Hospital, S-751 85 Uppsala, Sweden. This research was supported by grants from the Swedish Cancer Society.     

A prospective study of lifestyle factors and the risk of pancreatic cancer in Nord-Trøndelag, Norway

Objectives: Cancer of the pancreas is highly fatal and, despite extensive scrutiny, only cigarette smoking stands out as a likely causal agent in epidemiological studies. To explore to what extent different lifestyle factors are associated with the risk of pancreatic cancer, data from a large health screening survey in a county in Norway were analyzed. Methods: Our study included 31,000 men and 32,374 women initially free from any diagnosed cancer, and during 12 years of follow-up, 166 incident cases of pancreatic cancer were diagnosed at the Cancer Registry. Results: Compared with never smokers, we found a two-fold increased risk among current smokers, and a dose–response association with number of cigarettes (p for trend = 0.02 for both men and women) and with number of pack-years (p for trend = 0.02 for men and 0.01 for women). The risk among former smokers quitting more than 5 years before study entry was close to the risk of never smokers. Compared with persons who reported never or infrequently to be physically worn out after a day's work, the relative risk (RR) among those who nearly always became worn out was 2.9 (95% confidence interval (CI) = 1.4–5.8) for men and 3.8 (95% CI = 1.6–9.2) for women. Divorced or separated men had a risk of 3.1 (95% CI = 1.3–7.2) compared with married men. We observed a higher risk among women in occupations of high socioeconomic status (RR = 2.5; 95% CI = 1.2–5.2), and among men occupied in farming, agriculture or forestry (RR = 2.1; 95% CI = 1.1–4.0), compared with persons in occupations of low socioeconomic status. Conclusions: Our results confirm the findings of previous studies that indicate a causal role of cigarette smoking in pancreatic cancer. Moreover, we found that the risk of former smokers may approach the risk of never smokers within a few years subsequent to quitting.