A case-control study of thyroid cancer in women under age 55 in Shanghai (People's Republic of China)

A population-based interview study of 207 case-control pairs investigated reproductive, dietary, and other factors thought likely to increase thyroid cancer risk among women of reproductive age in Shanghai. Of particular interest were factors that might help explain the striking female over male excess in this age group. Risk was strongly associated with prior goiter or benign nodules (odds ratio [OR]=7.0, 95 percent confidence interval [CI]=2.5–27.5) and miscarriage as outcome of first pregnancy (OR=9.9, CI=2.0–48.4). Weaker associations were seen for women who were ever-pregnant (OR=2.1, CI=1.1–4.2), ever had an induced abortion (OR=1.6, CI=0.9–2.9), and ever used oral contraceptives (OR=1.7, CI=1.0–3.1). Compared with controls, cases gained significantly more weight from menarche to highest nonpregnant weight (P trend <0.01). Overall, cases ate more fish and shellfish, but there was no trend with level of consumption. More cases had a parent, sibling, or child with thyroid disease (OR=5.2, CI=2.5–12.1). Our findings relating to goiter and benign nodules and various reproductive factors support earlier studies. Consumption of seafood was difficult to evaluate; more detailed dietary data are needed to assess iodine intake.Drs Preston-Martin, Duda, and Mack are at the University of southern California School of Medicine, Los Angeles, CA, USA. Dr Jin is with the Shanghai Cancer Institute, Shanghai, People's Republic of China. Address correspondence to Dr Preston-Martin at the Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033, USA. This project was partially supported by awards SIG-2 and FRA-329 from the American Cancer Society.     

Recent oral contraceptive use and risk of breast cancer (United States)

We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n=6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n=9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR]=1.1, 95 percent confidence interval [CI]=10–1.2). Total duration of usealso was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI=0.9–1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR=2.0, CI=1.1–3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m²) less than 20.4, RR=1.7, CI=1.1–2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.Authors are with the University of Wisconsin Comprehensive Cancer Center, Madison, WI, USA (Dr Newcomb, Ms Trentham Dietz); NIEHS Epidemiology Branch, Research Triangle Park, NC (Dr Longnecker); Fred Hutchinson Cancer Research Center, Seattle, WA (Dr Surer); Department of Obstetrics and Gynecology, Pritzker School of Medicine, The University of Chicago, Chicago, IL (Dr Mittendorf); Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH (Dr Baron); Boston University, School of Public Health, Boston, MA (Dr Clapp); Department of Epidemiology and Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Harvard Medical School and Department of Medicine, Brigham and Women's Hospital, Boston, MA (Dr Willett). Address correspondence to: Dr Polly A. Newcomb, University of Wisconsin-Madison Comprehensive Cancer Center, 1300 University Ave., #4780, Madison, WI 53706, USA. Supported by Public Health Service (National Cancer Institute) grants R01 CA 47147 and R01 CA 47305.     

Family history of cancer and seizures in young children with brain tumors: a report from the Childrens Cancer Group (United States and Canada)

The occurrence of cancer and neurological disorders in first- and second-degree relatives of children in the United States and Canada diagnosed with brain tumor before age six was investigated. A pair-matched casecontrol study with 155 astrocytoma and 166 primitive neuroectodermal tumor (PNET) cases was performed. Cases were identified through the Childrens Cancer Group. Controls were selected by random-digit dialing and matched to cases on age, race, and telephone area code and exchange. Childhood cancers were more common in PNET relatives compared with the general population (standardized incidence ratio [SIR]=2.5, 95 percent confidence interval [CI] 1.1–4.8, P=0.02) and with control relatives (odds ratio [OR]=3.0, CI=0.5–30, P=0.29). For astrocytoma, nonsignificant excesses of brain tumor, leukemia/lymphoma, and childhood cancer occurred among case relatives compared with control relatives, but not compared with the general population. Astrocytoma cases were significantly more likely than controls to have a relative with seizures (OR=2.5, CI=1.2–4.9, P=0.009), especially childhood seizures (OR=3.4, CI=1.2–12, P=0.02), epilepsy (OR=3.0, CI=0.9–13, P=0.08), and febrile convulsions (OR=4.5, CI=0.9–43, P=0.07). A family history of stroke was not a risk factor for either type of brain tumor. These results suggest that some childhood brain tumors may result from a genetic susceptibility and that some risk factors may affect childhood astrocytoma and PNET differently.Drs Rorke, Meadows, and Bunin are with the Children's Hospital of Philadelphia, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA. Dr Kuijten was at the Children's Hospital of Philadelphia but is now at McKinsey and Company, Amsterdam, The Netherlands. Dr Strom is with The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. Dr Boesel is with Columbus Children's Hospital, Columbus, OH, USA. Dr Buckley is with the School of Medicine, University of Southern California, Los Angeles, CA, USA. Address correspondence to The Childrens Cancer Group, P.O. Box 60012, Arcadia, CA 91066-6012. Work was performed at the Children's Hospital of Philadelphia, Division of Oncology, Department of Pediatrics, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA. This research (Childrens Cancer Group protocol No. E12) was supported in part by US National Institutes of Health grant CA 29275. Contributing Childrens Cancer Group Investigators, Institutions, and Grant Numbers are given in the Appendix. Grant support from the Division of Cancer Treatment, National Cancer Institutes of Health, Department of Health and Human Services. The work reported in this paper was undertaken during the tenure of a Research Training Fellowship awarded to Dr Kuijten by the International Agency for Research on Cancer, World Health Organization, Lyon, France.     

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.     

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.     

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.     

Reproductive factors and risk of brain,colon, and other malignancies in Iowa (United States)

The influence of parity on the risk of cancers of the female breast and reproductive organs is well established. However, non-reproductive sites have received less attention. Mail questionnaire data gathered from incident female cases (169 brain; 332 colon; 260 rectal; 145 kidney; and 169 pancreas cancers), and 821 populationbased controls in Iowa (United States) were used to measure the effect of parity and age at first birth on risk of these malignancies. Relative to nulliparous women, ever-parous women were at significantly decreased risk of brain cancer (odds ratio [OR]=0.44, 95 percent confidence interval [CI]=0.3–0.7) and of colon cancer (OR=0.67, CI=0.5–0.97), after adjustment for age and other risk factors. The OR for the other sites did not differ significantly from 1.0. The lower risk of brain cancer among parous women was similar in younger and older age groups, in patients diagnosed with glioblastoma and astrocytoma, and among ever- and never-smokers. The findings for colon cancer are consistent with observations from other studies. In the context of limited laboratory and clinical evidence implicating hormones in brain neoplasia, these findings may suggest a role for hormonal factors in brain cancer etiology. Hormonal factors deserve more detailed future consideration as risk factors in brain cancer.Dr Cantor is with the Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. Dr Lynch and Ms Johnson are with the Department of Preventive Medicine and Environmental Health, University of Iowa, Iowa City, IA, USA. Address correspondence to Dr Cantor, Environmental Epidemiology Branch, National Cancer Institute, Executive Plaza North, Suite 443, Bethesda, MD 20892, USA. Supported in part by United States National Cancer Institute research contracts (NCI-NO1-CP-51026 and NCI NO1-CP-85614) and by a Public Health Service Preventive Oncology Academic Award (5 KO7 CA01181-05).     

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.     

Parity and risk of thyroid cancer: a nested case-control study of a nationwide Swedish cohort

The association between parity and risk of thyroid cancer was examined in a case-control study nested within a cohort of Swedish women born 1925–60. A total of 1,409 cases of thyroid cancer were compared with 7,019 agematched controls. Odds ratios (OR) and 95 percent confidence intervals (CI) were calculated as estimates of relative risk. A weak association was found between parity and risk of thyroid cancer (OR for ever-parous women cf nulliparous was 1.1, CI=1.0–1.3). For the subset of papillary cancers, there was a significantly increased risk (OR for ever-parous cf nulliparous = 1.3, CI=1.0–1.6), and among women diagnosed at the age of 50 or older, there was a positive linear trend with increasing number of livebirths. Women during the first year after a livebirth had an increased risk of thyroid cancer compared with women who delivered 10 or more years before; this association was most prominent among uniparous women (OR=2.5, CI=1.1–5.9). An increased risk was also apparent for age over 20 years at livebirth (among uniparous women) and age over 25 years at last livebirth (among multiparous women). A negligible effect of parity on thyroid cancer risk was seen, but each livebirth may have a short-term and age-dependent promoting effect.Authors are with the Department of Cancer Epidemiology, University Hospital, Uppsala, Sweden (M.R. Galanti, M. Lambe, A. Ebbora, R. Sparda B. Pettersson): Department of Social Medicine, University Hospital, Uppsala, Sweden (M. Lambe); Department of Epidemiology, Harvard School of Public Health, Boston, USA (A. Ekbom). Address correspondence to Dr M. Rosaria Galanti, Department of Cancer Epidemiology, University Hospital, S-751 85 Uppsala, Sweden. This work was supported in part by grant n. 3136-B92-02XBB from the Swedish Cancer Society.     

Diet,alcohol, and smoking and the occurrence of hyperplastic polyps of the colon and rectum (United States)

Hyperplastic polyps of the colon reveal a geographic distribution similar to that of colorectal cancer and adenomatous polyps. However, unlike adenomas—known precursors of colorectal cancer—little is known about the etiology or clinical significance of the hyperplastic polyp. In this prospective study, we set out to determine the main dietary and other lifestyle factors in the United States that might be associated with this lesion. Hyperplastic polyps of the distal colon and rectum were diagnosed in 219 of 12,922 men of the Health Professionals Follow-up Study having had an endoscopic procedure between 1986 and 1992, and 175 of 15,339 women of the Nurses' Health Study who had undergone an endoscopy for a variety of reasons between 1980 and 1990. After adjusting for age, family history of colon cancer, history of previous endoscopy, and total energy intake using multiple logistic regression, those consuming 30 g or more of alcohol per day were at increased risk relative to nondrinkers among men (relative risk [RR]=1.69; 95 percent confidence interval [CI]=1.01–2.80) and women (RR=1.79, CI=1.02–3.15). Current smoking also was found to be associated strongly positively with hyperplastic polyps in men (RR=2.45, CI=1.59–3.75) and women (RR=1.96, CI=1.16–2.86). High intake of folate was associated inversely with risk in both men (RR=0.74, CI=0.49–1.11, between high and low intakes of folate) and women (RR=0.45, CI=0.28–0.74, between high and low intakes of folate). Among macronutrients, a suggestive increase in risk existed with intake of animal fat, although this was attenuated in the full multivariate model (RR[men]=1.48, CI=0.94–2.41, and RR [women]=1.22, CI=0.77–1.94) between high and low quantities of animal fat intake. These prospective data provide evidence of associations between low folate intake, alcohol consumption, and current cigarette smoking, and risk of hyperplastic polyps of the distal colon and rectum. These same factors also have been found to be related to adenoma and cancer of the colon. The hyperplastic polyp is an indicator of populations at high risk for colorectal carcinoma, and it also may serve as a marker for factors that influence neoplastic evolution.Drs Giovannucci, Stampfer, Colditz, and Willett are with the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Authors also are affiliated with: the Department of Nutrition, Harvard School of Public Health, Boston, MA (Drs Kearney, Rimm, Stampfer, Ascherio, and Willett); the Department of Epidemiology, Harvard School of Public Health (Drs Rimm, Stampfer, Colditz, Ascherio, and Willett); and the Department of Surgery, New England Deaconess Hospital, Boston, MA (Dr Bleday). Address correspondence to Dr Giovannucci, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115, USA. This project was supported by research grants number CA 55075 and HL 35464 from the National Institutes of Health and Special Institution Grant No. 18 from the American Cancer Society. Dr Colditz. was supported by a Faculty Research Award (FRA-398) from the American Cancer Society.     

Previous cancer and radiotherapy as risk factors for lung cancer in lifetime nonsmokers

A history of previous primary cancer and of radiotherapy were investigated as risk factors for lung cancer in lifetime nonsmokers in a hospital-based case-control study. By design, subjects with a previous tobacco-related primary (of the lung, larynx, oropharynx, esophagus, kidney, bladder, or pancreas) were excluded. Information was available on 30 male and 47 female lung cancer cases and 87 male and 132 female controls, all lifetime nonsmokers, interviewed in hospitals in four United States cities between 1985 and 1990. In males, neither a history of a previous primary nor a history of radiotherapy was associated significantly with lung cancer; however, the numbers of exposed cases were small. In females, after adjustment for age, education, hospital, lifetime environmental tobacco-smoke exposure, and body mass index, both a history of a reproductive primary and a history of radiotherapy were associated significantly with lung cancer (odds ratio [OR]=4.9,95 percent confidence interval [CI]=1.4–17.7, and OR=4.4, CI=1.3–15.1, respectively). Due to a high correlation between a history of a reproductive primary and a history of radiotherapy in the cases, it was not possible to estimate the effect of one exposure independent of the other. These results are consistent with the possibility that endocrine factors may play a role in some lung cancers in women.Dr Kabat is with Albert Einstein College of Medicine, Bronx, NY, USA. At the time of this work, the author was in the Division of Epidemiology, American Health Foundation, New York, NY, USA. Address correspondence to Dr Kabat, Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Belfer Building, Rm 1302, 1300 Morris Park Avenue, Bronx, NY 10461-1602, USA. This work was supported by US National Cancer Institute Program Project grant CA32617 and Center grant CA17613.     

Obesity in youth and middle age and risk of colorectal cancer in men

To investigate an association between colon cancer and obesity during early adulthood—a potentially important period in the etiology of this disease—the authors assembled, by computer linkage, a population-based historical cohort of 52,539 men born between 1913 and 1927 residing in Hawaii (USA), for whom weight and height had been recorded in 1942–43 and 1972. Linkage of this cohort to the Hawaii Tumor Registry resulted in the identification of 737 incident cases of colorectal cancer for 1972–86. An average of 3.8 cancer-free controls were matched to each case on month and year of birth and ethnicity of the parents. A case-control analysis in each anatomic subsite of the large bowel revealed that both early and middle-age body mass increased the risk of sigmoid cancer in men in a dose-dependent fashion. The odds ratios (OR) for sigmoid cancer for the highest compared with the lowest tertiles of Quetelet index were: 2.1 (95 percent confidence interval [CI]=1.4–3.2) and 1.7 (CI=1.1–2.5), at ages 15–29 and in prediagnostic years, respectively. These associations were additive and idependent of socioeconomic status. Men who were above the median Quetelet index in 1942 and 1972 had an OR of 2.7 (CI=1.8–4.0), compared with those who were below the median in both periods. This study provides further evidence for an association of obesity with colon cancer in men and suggests that this association is limited to the sigmoid colon and may be related to both early and late events of colon carcinogenesis.The authors are with the Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii. Address correspondence to Dr Le Marchand, Epidemiology Program, Cancer Research Center of Hawaii, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA. This work was supported in part by Public Health Service grant 5-R29-CA44503 and contract NO1-CN-55424 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.     

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).     

Bladder cancer,parity, and age at first birth

The excess of bladder cancer in males (M:F ratio of 4:1 in the United States) is not explained fully by gender differences in smoking habits or occupational exposures. Laboratory studies suggest that some androgenic hormones stimulate (or do not inhibit) oncogenesis in bladder tissue, and that estrogenic hormones have the opposite effect. These observations suggest that bladder cancer risk in females may be modified by sex hormones which undergo profound changes during and following pregnancy. Mail-questionnaire data from 317 incident female cases, and 833 population-based controls in Iowa were used to measure the effect of parity and maternal age at first birth on bladder cancer risk. Parous women were at decreased risk relative to nulliparous women (odds ratio [OR]=0.67, 95 percent confidence interval [CI]=0.44–1.00), after adjustment for age, tobacco use, and previous bladder infection. The overall risk reduction was restricted to women who had never smoked (OR=0.51, CI=0.30–0.88), with no apparent effect of parity among ever-smokers (OR=0.93, CI=0.49–1.77). Risk appeared to decrease with increasing age at first birth, but did not vary with increasing parity after the first birth. Our findings are consistent with the hypothesis that oncogenesis in transitional cell tissue of the human bladder is influenced by sex hormones, and that hormonal changes related to pregnancy thereby can decrease risk.Dr Cantor is with the Environmental Epidemiology Branch, National Cancer Institute. Dr Lynch and Ms Johnson are in the Department of Preventive Medicine, University of Iowa School of Medicine, Iowa City, Iowa. Address correspondence to Dr Cantor at NCI, Executive Plaza North, Suite 443, Bethesda, MD 20892, USA. This research was supported in part by National Cancer Institute research contracts NCI-NO1-CP-51026 and NCI-NO1-CP-85614, and by a Public Health Service Preventive Oncology Academic Award, 5 KO7 CA01181-04.     

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.     

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.     

Dietary associations in a case-control study of endometrial cancer

Despite the established role of obesity in the etiology of endometrial cancer, limited data are available from analytical epidemiologic studies on the association of risk with dietary factors. A case-control study of 399 cases and 296 controls conducted in five areas of the United States from 1 June 1987 to 15 May 1990, enabled evaluation of risk related to dietary intakes adjusted for potential confounders. Caloric intake was associated modestly with increased risk (odds ratio [OR]=1.5,95 percent confidence interval [CI]=0.9–2.5 for highest cf lowest quartiles of intake), with the principal contributors being fat and protein calories. After adjustment for other risk factors, including body mass, increased risk was associated with higher intakes of fat. Several components of fat investigated were associated with increased risk, although associations were slightly stronger for saturated fat (OR=2.1, CI=1.2–3.7) and oleic acid (OR=2.2, CI=1.2–4.0) than for linoleic acid (OR=1.6, CI=0.9–2.8). Food-group analyses showed intake of complex carbohydrates—and specifically of breads and cereals—associated with reduced risks (OR=0.6, CI=0.4–1.1), whereas animal fat and fried foods were associated with elevated risks (OR=1.5 and 1.7, respectively). The relations of endometrial cancer with animal fat and complex carbohydrates were independent. No consistent associations were noted for intakes of cholesterol, fiber, vitamins A and C, individual carotenoids, or folate-rich foods. These data imply an etiologic role for a diet rich in total fat and/or animal fat and low in complex carbohydrates with endometrial cancer. These associations are consistent with a hormonal mechanism and were independent of the associations of obesity and other risk factors.Drs Potischman, Swanson, Brinton, and Hoover are with the Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. Authors are also affiliated with Information Management Services, Inc., Silver Spring, MD (Ms McAdams), and the Departments of Obstetrics and Gynecology at Bowman Gray School of Medicine, Winston-Salem, NC (Dr Barrett); University of California at Irvine Medical Center, Irvine, CA (Dr Berman); Milton S. Hershey Medical Center, Hershey, PA (Dr Mortel); University of Minnesota Medical School, Minneapolis, MN (Dr Twiggs); Rush Medical College, Chicago, IL (Dr Wilbanks). Address correspondence to Dr Potischman, Nutritional Epidemiology Section, Division of Cancer Etiology, National Cancer Institute, Executive Plaza North, Suite 443, Bethesda, MD 20892, USA.     

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.     

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.