A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States)

To evaluate predictors of contralateral breast cancer risk, we examined data from a nested case-control study of second primary cancers among a cohort of women in western Washington (United States) diagnosed with breast cancer during 1978 through 1990 and identified through a population-based cancer registry. Cases included all women in the cohort who subsequently developed contralateral breast cancer at least six months after the initial diagnosis, but prior to 1992 (n=234). Controls were sampled randomly from the cohort, matched to cases on age, stage, and year of initial breast cancer diagnosis. Information on potential risk factors for second primary cancer was obtained through medical record abstractions and physician questionnaires. Women who were postmenopausal due to a bilateral oophorectomy (i.e., a surgical menopause) at initial breast cancer diagnosis had a reduction in contralateral breast cancer risk compared with premenopausal women (matched odds ratio [mOR]=0.25, 95 percent confidence interval [CI]=0.09–0.68), whereas no reduction in risk was noted among postmenopausal women who had had a natural menopause (mOR=0.90, CI=0.39–2.09). Among postmenopausal women, there was a suggestion of a lower risk associated with relatively high parity (2+). A family history of breast cancer was associated with an increased risk (mOR=1.96, CI=1.22–5.15) and varied little by menopausal status. Having an initial tumor with a lobular component (c.f. a ductal histology) was not related strongly to risk (mOR=1.47, CI=0.79–2.74). The results of the present and earlier studies argue that we have limited ability to predict the occurrence of a contralateral breast tumor. Better predictors will be required before diagnostic and preventive interventions can be targeted to subgroups of patients with unilateral breast cancer.Authors are with the Department of Epidemiology, University of Washington, Seattle, WA, USA (Drs Cook, White, Schwartz, Daling, Weiss); with the Fred Hutchinson Cancer Research Center, Seattle, WA (Drs Cook, White, Schwartz, McKnight, Daling, Weiss); and the Department of Biostatistics, University of Washington, Seattle, WA (Dr McKnight). Address correspondence to Dr Cook, MP-381, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104, USA. This research was supported in part by grants from the US National Cancer Institute (R35 CA 39779), the Agency for Health Care Policy and Research (1 RO3 HS08004-01), 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.     

Breastfeeding and breast cancer risk

A population-based case-control study of breast cancer with a focus on premenopausal women under 45 years of age, conducted in three geographic regions of the United States, enabled the evaluation of risk in relation to varying breastfeeding practices. Among premenopausal parous women (1,211 cases, 1,120 random-digit-dialing controls), a history of breastfeeding for two or more weeks was associated with a relative risk (RR) of 0.87 (95 percent confidence interval [CI]=0.7–1.0). This relationship was not altered substantially by removing from the reference group women who had problems with breastfeeding in the first two weeks, including those with insufficient milk production. Risk was not related substantially to number of children breastfed or length of breastfeeding, although a relatively low risk was observed among those breastfeeding for the longest duration examined (RR=0.67, CI=0.4–1.1 for an average period per child of 72 or more weeks). Women who began to breastfeed at a young age (<22 years) experienced the greatest reduction in risk, but other timing parameters (e.g., interval since first or last breastfeeding) were not predictive of risk. Risks were not modified substantially by age or menopause status, although the number of menopausal subjects examined was limited. Use of medications to stop breast milk was unrelated to risk (RR=1.04). The results of this study do not support the notion that breastfeeding substantially reduces breast cancer risk; however, this may reflect the fact that most of our study subjects breastfed only for limited periods of time (average breastfeeding per child of 30 weeks). Further studies are needed to clarify the relationship of breastfeeding to breast cancer risk, and to determine possible etiologic mechanisms underlying any observed associations.Drs Brinton, Potischman, and Swanson are with the Environmental Epidemiology Branch, National Cancer Institute, Betbesda, MD, USA. Authors also are affiliated with the Special Epidemiology Program, New Jersey State Department of Health, Trenton, NJ, USA (Ms Schoenberg); Rollins School of Public Health, Emory University, Atlanta, GA, USA (Dr Coates); the Division of Epidemiology, Columbia University School of Public Health, New York, NY, USA (Dr Gammon); and the Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA (Drs Malone, Stanford, Daling). Address correspondence to Dr Brinton, Environmental Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 443, Bethesda, MS 20892, USA.     

Epidemiology of the M-component immunoglobulin types of multiple myeloma

The purpose of this population-based case-control study was to learn whether risk factors differ for the individual immunoglobulin types of multiple myeloma. In particular, we sought to determine whether IgA and IgG myeloma were related to a history of exposure to reported IgA- and IgG-stimulating conditions, respectively, or to a history of selected occupational and physicochemical exposures. The M-component immunoglobulin type was determined from immunoelectrophoresis as reported in medical records, and exposure status was obtained through in-person interviews. IgG (56 percent) and IgA (22 percent) M-components predominated. For 17 percent of cases, no peak was found on immunoelectrophoresis; they were presumed to have light-chain myeloma. Persons with these three types of myeloma did not differ with respect to distributions of age or race, but a somewhat higher proportion of light-chain cases were women (58 percent cf 45 percent of all other cases). Detailed analysis of the IgA and IgG subtypes provided little evidence that they differ with respect to prior immune stimulation or employment in several specific jobs. IgA myeloma, but not IgG myeloma, was associated modestly with a history of exposure to chest and dental X-rays. Our study provides little evidence that IgA and IgG myeloma differ with respect to the risk factors examined.Ms Herrinton and Drs Koepsell, Weiss, and Daling are with the Department of Epidemiology, University of Washington, Seattle, WA, USA, and the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Dr Demers is with the Department of Environmental Health, University of Washington, Seattle, WA, USA. Dr Taylor is with Group Health Cooperative of Puget Sound, Seattle, WA, USA. Dr Lyon is with the School of Medicine, University of Utah, Salt Lake City, UT, USA. Dr Swanson is with the Cancer Center, Michigan State University, East Lansing, MI, USA. Dr Greenberg is with the School of Public Health, Emory University, Atlanta, GA, USA. Address correspondence to Ms Lisa Herrinton, Fred Hutchinson Cancer Research Center, 1124 Columbia MP-381, Seattle, WA 98104, USA. The project was supported by grants CA23350, CA39779, and CA09168 from the US National Cancer Institute.     

Cutaneous melanoma following cervical intra-epithelial neoplasia in western washington state

Stimulated by a recent report from a Norwegian pathology institute of an excess risk of melanoma among women with cervical neoplasia, we analyzed the relevant data from a population-based cancer registry serving western Washington State (United States). Among 11,693 women diagnosed with cervicalintra-epithelial neoplasia (CIN) between 1974 and 1989 who were followed-up for at least a year, 14 cases of cutaneous melanoma were identified, in comparison with 13.7 cases expected (relative risk=1.0,95 percent confidence interval=0.5-1.7) based on the rates of melanoma among all women who resided in this area. While these results are at odds with those recently reported from the pathology institute, they are similar to those obtained in previous cancer-registry studies in several countries, which found little or no excess occurrence of melanoma following cervical cancer.Authors are with the Department of Epidemiology, University of Washington, Seattle, WA, USA. Drs Weiss and Schwartz are also with the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Address correspondence to Dr Weiss, Department of Epidemiology, SC-36, University of Washington, Seattle, WA 98195, USA. This investigation was supported by PHS grant numbers 5T32 CA09168-17 and R35 CA39779 awarded by the US National Cancer Institute, DHHS.     

Type of postmenopausal hormone use and risk of breast cancer: 12-year follow-up from the Nurses' Health Study

We prospectively examined the use of hormone replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 12 years of follow-up (480,665 person-years) among postmenopausal women, 1,050 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk. After adjustment for established risk factors, type of menopause, age at menopause, and current age, the rate ratio (RR) was 0.91, 95 percent confidence interval (CI) = 0.78–1.07. the risk of breast cancer was elevated significantly among current users (RR = 1.33, CI = 1.12–1.57); after adjusting for age, we observed no evidence of increasing risk with increasing duration of use among current users (P trend = 0.41), or among past users (P trend = 0.46). Women currently using unopposed estrogen (RR = 1.42, CI = 1.19–1.70), estrogen and progesterone (RR = 1.54, CI = 0.99–2.39), or progesterone alone (RR = 2.52, CI = 0.66–9.63), were all at increased risk of breast cancer compared with never users. These data suggest that long-term past use of estrogen replacement therapy is not related to risk, that current estrogen use increases risk of breast cancer to a modest degree, and that the addition of progesterone does not remove the increased risk observed with current use of unopposed estrogen.The authors are with the Nurses' Health Study, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA; and Harvard Medical School, Boston, MA, USA. Address correspondence to Dr Colditz, Channing Laboratory, 180 Longwood Ave., Boston, MA 02115-5899, USA. Supported by research grant CA40356 from the National Cancer Institute, NIH, Department of Health and Human Services. Dr Colditz is supported by an American Cancer Society Faculty Research Award FRA-398.     

Childhood leukemia in the vicinity of Canadian nuclear facilities

An ecologic study was conducted to determine whether leukemia rates among children born to mothers residing in the vicinity of Ontario (Canada) nuclear facilities differed from the provincial average. Childhood leukemia mortality and incidence ratios for the period 1950 to 1987 were examined for five regions within 25 km of a nuclear facility. The nuclear facilities included a research development facility, a uranium refinery, a uranium mining and milling facility, and two nuclear-power generating stations. Overall, the observed number of leukemia deaths (O=54) was slightly greater than expected (E=46.1) during the period when the facilities operated, but the difference was not statistically significant (O/E=1.17,95 percent confidence interval [CI]=0.88–1.53). There was no indication of a birth cohort effect, as the mortality ratios based on place of birth were not significantly greater than the mortality ratios based on place of death. In the analyses of individual facilities, CIs included the null value and were generally wide because of the small observed and expected numbers; however, in the vicinity of the nuclear generating stations, the observed relative excess of leukemia deaths (O=36, O/E=1.40) had a lower confidence limit that was close to the null value.Drs McLaughlin, Clarke, and Nishri are with the Ontario Cancer Treatment and Research Foundation, Toronto, Ontario, Canada; Drs McLaughlin and Clarke are affiliated also with the University of Toronto, Dr Anderson is with the University of British Columbia, Vancouver, Canada. Address correspondence to Dr McLaughlin, Ontario Cancer Treatment and Research Foundation, 7 Overlea Boulevard, Toronto, Ontario, Canada M4H-1A8. This research project was conducted in the Division of Epidemiology and Statistics of the Ontario Cancer Treatment and Research Foundation. Financial support was received from the Atomic Energy Control Board of Canada.     

Incidence of male genital skin tumors: Lack of increase in the United States

In men, genital exposure to ultraviolet radiation (UVR) has been hypothesized to increase the risk of nonmelanotic skin tumors at that site. However, during the period 1973–86, no change in the incidence of penile or scrotal skin tumors occurred in the United States, despite a likely increase in the population's level of genital exposure to UVR through the use of sunlamps and sunbeds. While UVR in conjunction with use of 8-methoxypsoralen by men with psoriasis is clearly related to an increase in the incidence of male genital skin tumors, our data provide no support for the hypothesis that, among men in general, UVR alone has this same effect.Drs Goldoft and Wesiss are with the Department of Epidemiology, SC-36, University of Washington, Seattle, WA 98195 USA. Address correspondence to Dr Weiss. This investigation was supported by PHS grants number 1 R35 CA39779 and 5 T32 CA09168 awarded by the National Cancer Institute, DHHS.     

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.     

The incidence of non-Hodgkin's lymphoma and its histologic subtypes in Asian migrants to the United States and their descendants

We examined the incidence of non-Hodgkin's lymphoma (NHL) in Chinese, Japanese, and Filipino residents of the United States to obtain further clues about the etiology of the disease. The age, race, and birthplace of residents of Hawaii, San Francisco/Oakland (California), and western Washington who had received a diagnosis of NHL during the period 1973–86 were obtained from population-based cancer registries, and a special tabulation from the 1980 Census was used to estimate the number of person-years at risk for each category of resident. The incidence of NHL in each of the Asian groups examined was 35 to 85 percent that of US-born Whites. However, there was no consistent trend of increasing incidence with increasing generation of residence in any of the groups. In Asian-Americans, the risk of small cell lymphocytic and plasmacytoid lymphoma was 10 to 85 percent that of Whites, although no clear trends of risk with generation of residence in the US were observed. They also were at a reduced risk of follicular lymphoma, and in Chinese and Japanese persons, the risk was lower in first generation than in later generation migrants (Chinese: Asian-born relative risk [RR]=0.11, US-born, RR=0.84; Japanese: Asian-born, RR=0.15, US-born, RR 0.36). The risk of diffuse lymphoma was similar in Chinese-and Japanese-Americans and US-born Whites. We conclude that, with the exception of follicular lymphoma, the basis for the relatively low incidence of NHL in Asian-Americans does not lie in exposures or characteristics that differ between the migrants themselves and their descendants.Dr Herrinton is with the Division of Research, Kaiser Permanente, Oakland, CA, USA. Dr Goldoft is with the Washington State Department of Health, Seattle, WA, USA. Drs Schwartz and Weiss are with the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, and the Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA. Address correspondence to Dr Herrinton, Division of Research, Kaiser Permanente, 3505 Broadway Ave., Oakland, CA 94611, USA. This work was supported by grants no. R 35 CA 39779 and R 35 CA 49761 from the US National Cancer Institute.     

Exogenous hormones,reproductive history,and colon cancer (Seattle,Washington, USA)

The associations between exogenous hormones, reproductive history, and colon cancer were investigated in a case-control study among women aged 30–62 years. The study was conducted in the Seattle, Washington (USA) metropolitan area between 1985 and 1989 and included 193 incident cases of colon cancer and 194 controls. There was little overall association between colon cancer and oral contraceptive use, parity, age at first birth, hysterectomy or oophorectomy status, or age at menopause. Use of noncontraceptive hormones at or after age 40, most likely hormone replacement therapy (HRT), was associated with decreased risk of colon cancer (adjusted odds ratio [OR]=0.60, 95 percent confidence interval [CI]=0.35–1.01), particularly among women with more than five years of use (OR=0.47, 95 percent CI=0.24–0.91). While results from previous studies have not been consistent, any protective effect of HRT against colon cancer would be important given the continuing debate over its potential risks and benefits.Support for this study was provided by grant CA44790. Mr Jacobs was supported by the Cancer Prevention Training Grant T32 CA09661. This study was performed at the Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA.     

Physical activity,medical history,and risk of testicular cancer (Alberta and British Columbia,Canada)

In order to evaluate risk factors for germ cell cancers, we conducted a case-control study of 510 men with testicular cancer aged 15 to 79 years and 996 randomly selected age-matched controls in the provinces of British Columbia and Alberta, Canada. Subjects completed a mailed questionnaire providing data on education level, ethnic origin, medical history, smoking, occupation, and recreational and sports activity. The response rate among cases was 80.3 percent and among controls was 68.1 percent. After controlling for age and ethnic origin, undescended testis was associated positively with risk of testicular cancer (odds ratio [OR]=3.5; 95 percent confidence interval [CI]=2.2–5.7) as was inguinal hernia requiring surgery (OR=2.0, CI=1.3–2.9), and hydrocoele (OR=2.6, CI=1.4–5.1). Risk of testicular cancer increased with height, with subjects taller than 180 cm having a significantly increased risk compared with those 174 cm or less (OR=1.5, CI=1.1–2.1). A moderate to high level of recreational activity level was associated inversely with testicular cancer risk (OR=0.6, CI=0.5–0.8).This project was supported by the National Health Research and Development Program (6610-1340-53) and by Health Canada through a contract from the Action Plan on Health and the Environment.     

Risk of endometrial cancer following cessation of menopausal hormone use (Washington, United States)

While there are a number of benefits to the health of postmenopausal women from use of unopposed estrogens, the increased risk of endometrial cancer related to these hormones has led many women to use combined estrogen-progestogen therapy instead, or not to use hormones at all. Most women who take hormones do so only in the early portion of their postmenopausal years, so the risk of endometrial cancer following cessation of use might bear heavily on the overal risk/benefit evaluation. We analyzed data from a case-control study of women in western Washington (United States) to assess the magnitude of excess risk of endometrial cancer following discontinuation of estrogen use. Cases (n=661) consisted of women aged 45 to 74 diagnosed between 1985 and 1991 who resided in one of three counties in Washington State. Controls (n=865) were identified by random-digit dialing. Subjects were interviewed in-person to ascertain current and prior hormone use. The analysis was restricted to women who had not received combined estrogen-progestin therapy. Among women who had used unopposed estrogens at some time, risk of endometrial cancer declined as time since last use increased. Nonetheless, even among women who used these hormones for just a few years, the risk remained elevated by 30 to 70 percent almost a decade after cessation. These results, combined with those of most (but not all) other studies of this issue, suggest that a woman who has discontinued unopposed estrogen therapy may retain a small increased risk of endometrial cancer for a long period of time.Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, the Department of Epidemiology, University of Washington Department of Biostatistics University of Washington, Seattle, WA. Department of Epidemiology, University of Washington, Seattle, WA 98195, USA. This research was supported by US National Cancer Institute contracts R01 CA47749 and R35 CA39779.     

An exploratory analysis of risk factors for childhood malignant germ-cell tumors: report from the Childrens Cancer Group (Canada,United States)

A study of 105 patients with childhood malignant germ-cell tumors (MGCT) and 639 community controls was conducted utilizing a large epidemiologic database collected by the Childrens Cancer Group from 25 member institutions in the United States and Canada. This study was designed to explore the risk factors of this malignancy whose etiology remains poorly understood. A structured, self-administered questionnaire was used to collect exposure information, and data were analyzed using an unconditional logistic regression model with adjustment for relevant confounders. Consistent with the findings from studies of adult MGCT, gestational age was associated inversely with risk of MGCT, with a 70 to 75 percent reduction in risk for children born at term compared with those born pre-term. Parental, particularly maternal, self-reported exposure to chemicals or solvents (odds ratio [OR]=4.6, 95 percent confidence interval [CI]=1.9–11.3) and OR=2.2, CI=1.1–4.7 for maternal and paternal exposure, respectively) and plastic or resin fumes (OR=12.0, CI=1.9–7.5.0 [maternal] and OR=2.5, CI=1.0–6.5 [paternal]) were associated with elevated risk of MGCT. New findings, not reported previously, include a positive relationship of MGCT risk with birthweight and prolonged breastfeeding, an inverse association between MGCT risk and number of cigarettes smoked by the mother during pregnancy, and a 3.1-fold increased risk (CI=1.5–6.6) associated with maternal urinary infections during index pregnancy. Although these findings need confirmation from future studies, they suggest a potential influence of in utero exposure to maternal endogenous hormones, parental environmental exposures, and maternal diseases during pregnancy in the development of childhood MGCT.Drs Shu, Nesbit, and Robison are affiliated with the Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN, USA. Drs Buckley and Krailo are affiliated with the Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, CA, USA. Contributing Childrens Cancer Group Investigators, Institutions, and Grant Numbers are given in the Appendix. Address correspondence to Dr Shu, Childrens Cancer Group, P.O. Box 60012, Arcadia, CA 91066-6012, USA. Grant support is from the US National Cancer Institute and the US Department of Health and Human Services.     

Risk factors for renal cell carcinoma: results of a population-based case-control study

For a case-control study of risk factors for renal cell carcinoma, a mailed questionnaire was used to collect data on 518 cases and 1,381 population-based controls in Ontario, Canada. Active cigarette smoking increased risk twofold among males (odds ratio estimate [OR]=2.0, 95 percent confidence interval (CI)=1.4–2.8) and females (OR=1.9, CI=1.3–2.6). Passive smoking appeared to increase risk somewhat among nonsmokers (males: OR=1.6, CI=0.5–4.7; females: OR=1.7, CI=0.8–3.4). A high Quetelet index (QI) was associated with a twofold increase in risk in both sexes, although this was based on reported weight at age 25 years for males (OR=1.9, CI=1.2–3.1) and five years prior to data collection for females (OR=2.5, CI=1.4–4.6). Diuretic use was associated with significantly increased risk among females, but not among males. Phenacetin use increased risk, while acetaminophen use was not associated with altered risk, although few subjects used either compound. Multiple urinary tract infections increased risk, but only significantly in females (OR=1.9, CI=1.2–2.9). Our data indicate the need for further exploration of passive smoking and diuretics as risk factors, as well as elucidation of mechanisms by which high lifetime QI and frequent urinary-tract infections might increase risk of this cancer.Des Kreiger, Marrett, and Darlington are with the Department of Preventive Medicine and Biostatistics, University of Toronto, and Division of Epidemiology and Statistics, Ontario Cancer Treatment and Research Foundation, Canada. Dr Dodds is with the Keproductive Care Program of Nova Scotia, formerly of the Ontario Cancer Treatment and Research Foundation, Canada. Ms Hilditch is with the Ontario Cancer Treatment and Research Foundation Epidemiology Research Unit, University of Toronto, Canada. Address correspondence to Dr Kreiger Department of Preventive Medicine and Biostatistics, 12 Queen's Park Crescent West, 3rd Floor, McMurrich Building, University of Toronto, Toronto, Ontario M5S 1A8, Canada. This study was funded by a grant #01692 of the Ontario Ministry of Health.     

Alcoholism and cancer risk: a population-based cohort study

The incidence of cancer was studied in a population-based cohort of 9,353 individuals (8,340 men and 1,013 women) with a discharge diagnosis of alcoholism in 1965–83, followed up for 19 years (mean 7.7). After exclusion of cancers in the first year of follow-up, 491 cancers were observed cf 343.2 expected through 1984 (standardized incidence ratio [SIR] = 1.4,95 percent confidence interval [CI] = 1.3–1.6). A similar excess risk of cancer was seen among men (SIR = 1.4, CI = 1.3–1.6) and among women (SIR = 1.5, CI = 1.1–2.0). We observed the established associations with cancers of the oral cavity and pharynx (SIR = 4.1, CI = 2.9–5.7), esophagus (SIR = 6.8, CI = 4.5–9.9), larynx (SIR = 3.3, CI = 1.7–6.0), and lung (SIR = 2.1, CI = 1.7–2.6), although confounding by smoking likely increased these risk estimates. While there was evidence of increased risk for pancreatic cancer (SIR = 1.5, CI = 0.9–2.3), alcoholism did not elevate the incidence of cancer of the stomach (SIR = 0.9, CI = 6–1.4), large bowel (SIR = 1.1, CI = 0.8–1.5), prostate (SIR = 1.0, CI = 0.8–1.3), urinary bladder (SIR = 1.0, CI = 0.6–1.5), or of malignant melanoma (SIR = 0.9, CI = 0.3–1.9). Among women, the number of breast cancers observed was close to expected (SIR = 1.2, CI = 0.6–2.2), although a significant excess number of cervical cancers occurred (SIR = 4.2, CI = 1.5–9.1). The results of this study, one of the first to evaluate the incidence of cancer in a population-based cohort of alcoholics of both sexes, are consistent with smaller previous studies, which were usually limited to cancer mortality and of short follow-up.Dr Adami is with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Drs McLaughlin and Hsing are with the Biostatistics Branch, National Cancer Institute, Bethesda, MD, USA. Dr Wolk is with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Dr Ekbom is with the Department of Surgery and with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Dr Persson is with the Department of Obstetrics and Gynaecology and with the Cancer Epidemiology Unit, University Hospital, Uppsala, Sweden. Address correspondence to Dr Adami, Cancer Epidemiology Unit, University Hospital, S-751 85 Uppsala, Sweden. The work was performed at the Cancer Epidemiology Unit, Uppsala University, Sweden; the research was supported by grants from the Swedish Cancer Society.     

Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States

This study examines the relationship between fatal breast cancer and use of estrogen replacement therapy (ERT) among women in a large prospective study in the United States. After nine years of follow-up, 1,469 breast cancer deaths were observedin a cohort of 422,373 postmenopausal women who were cancer free at study entry and who supplied information on estrogen use. Results from Cox proportional hazards modeling, adjusted for 11 other potential risk factors, showed that ever-use of ERT was associated with a significantly decreased risk of fatal breast cancer (rate ratio [RR]=0.84,95 percent confidence interval [CI]=0.75–0.94). There was a moderate trend (P=0.07) of decreasing risk with younger age at first use of ERT. This decreased risk was most pronounced in women who experienced natural menopause before the age of 40 years (RR=0.59, CI=0.40–0.87). There was no discernible trend of increasing risk with duration of use in estrogen users at baseline or former users, nor was there any trend in years since last use in former users. The relationship between ERT and breast cancer mortality differed by age at menarche and by a self-reported history of breast cysts. No increased risk of fatal breast cancer with ERT was observed with estrogen use status (baseline/former), age at first use, duration of use, or years since last use. These findings suggest that ever-use of ERT is associated with a 16 percent decreased risk of fatal breast cancer.     

Alcoholism and cancer of the larynx: a case-control study in western Washington (United States)

Alcohol consumption is a well-known risk factor for laryngeal cancer. To determine whether alcoholism, as measured by responses to the Michigan alcoholism screening test (MAST), is a risk factor for laryngeal cancer independent of alcohol consumption, we analyzed data from a population-based case-control study. Personal interviews were conducted with 235 patients (81 percent response rate) with laryngeal cancer diagnosed from September 1983 through February 1987, who were residents of the Seattle metropolitan area. A total of 547 controls frequency-matched by age and gender, selected by random-digit dialing, were interviewed (75 percent response rate). When considered in a multivariate model, independent risk factors for laryngeal cancer included: alcohol consumption (42 or more drinks/wk compared with seven or less drinks/wk: odds ratio [OR]=3.1,95 percent confidence interval [CI]=1.2–7.9); cigarette use (40 or more cigarettes/day compared with never-smoked: OR=23.1, CI=9.4–52.6); and weighted positive responses to the MAST (score of five or more compared with score of zero: OR=1.9, CI=1.1–3.4). Possible explanations for the association between alcoholism and laryngeal cancer are that a measure of alcoholism improves the accuracy of assessment of alcohol consumption, that alcoholism is associated with a pattern of alcohol consumption that increases the risk of laryngeal cancer, or that alcoholism may be a marker for host susceptibility to the carcinogenic effects of alcohol.conducted this work while with the School of Public Health and Community Medicine, University of Washington, Seattle, WA (USA)This research was supported in part by grants # RO1-CA-30022 and R37-CA-41530, and contract # NO1-CN-05230 from the US National Cancer Institute.     

Maternal exposure to potential inhibitors of DNA topoisomerase II and infant leukemia (United States): A report from the Children's Cancer Group

Nearly 80 percent of infant leukemias present with an abnormality involving the MLL gene at 11q23. Moreover, secondary acute myeloid leukemias (AML) that occur as the result of chemotherapy agents, which are known to inhibit DNA topoisomerase II, often manifest the same MLL abnormalities. It has been hypothesized that de novo infant leukemias may occur as a result of maternal exposure to agents in diet and medications that inhibit DNA topoisomerase II. Three epidemiologic studies of childhood leukemia with similar methodologies were conducted in the United States and Canada over the past 10 years by the Children's Cancer Group (CCG). Of the total 771 mothers of infants diagnosed at one year of age or less (<12.5 months) who originally were interviewed (303 infant cases and 468 matched controls) across the three studies, follow-up questionnaire data on maternal exposure to potential DNA topoisomerase II inhibitors during pregnancy were available on 84 cases and 97 matched controls in the US. For maternal diet, a composite variable was created that consisted of 10 foods identified a priori as containing DNA topoisomerase II inhibitors. There were no significant trends with increasing maternal consumption for either the overall group, or the acute lymphoblastic leukemia (ALL) stratum. However, within the AML stratum, there was a statistically significant positive association (P trend=0.04) with increasing consumption of DNA topoisomerase II-inhibitor containing foods (odds ratio [OR]=9.8, 95 percent confidence interval [CI]=1.1–84.8; OR=10.2, CI=1.1–96.4; for medium and high consumption, respectively). Other potential topoisomerase II inhibitors were explored; no significant findings were found. Results of this preliminary study, in combination with molecular data, should be used in future investigations of childhood leukemia (particularly, infant) to justify the incorporation of a detailed dietary history.Drs Ross and Robison are with the Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN, USA. Dr Potter is with the Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Dr Reaman is with the Department of Pediatric Hematology-Oncology, Children's National Medical Center, Washington, DC. Dr Pendergrass is with the Department of Pediatric Hematology-Oncology, Children's Hospital and Medical Center, Seattle, WA. Address correspondence to Dr Ross, Children's Cancer Group, P.O. Box 60012, Arcadia, CA 91066-6012, USA. This research was supported in part by the University of Minnesota Children's Cancer Research Fund, NIH training grant T32 09607, and NCI grants CA42479, CA49450, CA58051 from the United States Department of Health and Human Services. Participating Children's Cancer Group investigators, institutions, and grant numbers (Division of Cancer Treatment, National Cancer Institute) are provided in the appendix.     

Moderate-to-vigorous intensity physical activity across the life course and risk of pre- and post-menopausal breast cancer

Moderate-to-vigorous intensity physical activity (MVPA) reduces breast cancer risk, although the effects of MVPA in different settings across the life course and how they may differ by menopausal status are unclear. This gap was addressed using data from a case–control study of 1,110 incident breast cancer cases and 1,172 cancer-free controls, frequency matched by age, from Vancouver and Kingston, Canada. In Vancouver, cases were recruited from the British Columbia Cancer Registry and controls from the Screening Mammography Program of British Columbia and in Kingston cases and controls were recruited from a breast assessment center. Lifetime leisure-time, household, and occupational MVPA energy expenditures were assessed in an open-ended questionnaire and mean weekly metabolic equivalent hours (MET-h/week) were calculated for the age periods 12–17, 18–34, 35–49, and ≥50 years and for the total lifetime. Odds ratios were estimated separately for pre- and for post-menopausal women using unconditional logistic regression. Among post-menopausal women, each of >22.9 MET-h/week of mean lifetime leisure-time MVPA (equivalent to running for 3 h) and >61.1 MET-h/week of mean lifetime household MVPA (equivalent to 24 h of moderate household work) reduced breast cancer risk by 40 %, compared to 0 MET-h/week of each. The respective ORs were 0.63 (95 % CI 0.42–0.94) and 0.58 (95 % CI 0.43–0.79). Among post-menopausal women, leisure-time MVPA after age 35 was more strongly associated with reduced breast cancer risk than MVPA in early life, while household MVPA was associated with reduced risk at all adulthood age periods. The weekly volume of leisure-time MVPA required to reduce post-menopausal breast cancer risk was consistent with amount recommended in the World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention.     

Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women.

BACKGROUND: Because unopposed estrogen substantially increases endometrial carcinoma risk, estrogen plus progestin is one menopausal hormone therapy formulation for women who have not had a hysterectomy. However, endometrial carcinoma risks among estrogen plus progestin users and among former unopposed estrogen users are not firmly established. METHODS: We evaluated endometrial carcinoma risks associated with estrogen plus progestin and unopposed estrogen therapies in 30,379 postmenopausal Breast Cancer Detection Demonstration Project follow-up study participants. We ascertained hormone therapy use and other risk factors during telephone interviews and mailed questionnaires between 1979 and 1998. We identified 541 endometrial carcinomas via self-report, medical records, the National Death Index, and state cancer registries. Poisson regression generated time-dependent rate ratios (RR) and 95% confidence intervals (95% CI). RESULTS: Endometrial carcinoma was significantly associated with estrogen plus progestin only use (n = 68 cancers; RR, 2.6; 95% CI, 1.9-3.5), including both sequential (progestin <15 days per cycle; n = 32 cancers; RR, 3.0; 95% CI, 2.0-4.6) and continuous (progestin at least 15 days per cycle; n = 15 cancers; RR, 2.3; 95% CI, 1.3-4.0) regimens. The RR increased by 0.38 (95% CI, 0.20-0.64) per year of estrogen plus progestin use, and RRs increased with increasing duration of use for both regimens. The strong association with unopposed estrogen use declined after cessation but remained significantly elevated > or =10 years after last use (RR, 1.5; 95% CI, 1.0-2.1). CONCLUSIONS: Both estrogen plus progestin regimens significantly increased endometrial carcinoma risk in this study. Risks among unopposed estrogen users remained elevated long after last use. The prospect that all estrogen plus progestin regimens increase endometrial carcinoma risk deserves continued research.