Physical activity, obesity, and risk of colorectal adenoma in women (United States)

The relationship between physical inactivity, body mass index (BMI) (wt[kg]/ht[m]²), and pattern of adipose distribution with risk of colorectal adenomas (precursors of cancer) was examined in 13,057 female nurses in the United States, 40 to 65 years of age in 1986, who had an endoscopy between 1986 and 1992. From 1986 to 1992, 439 participants were newly diagnosed with adenomas of the distal colorectum. After controlling for age, prior endoscopy, parental history of-colorectal cancer, smoking, aspirin, and intakes of animal fat, dietary fiber, folate, methionine, and alcohol, physical activity was associated inversely with risk of large (1 cm) adenomas in the distal colon (relative risk [RR]=0.57,95 percent confidence interval [CI]=0.30–1.08, comparing high and low quintiles of average weekly energy expenditure from leisure-time activities; P trend = 0.05). Much of the benefit came from activities of moderate intensity such as brisk walking. In addition, BMI was associated directly with risk of large adenomas in the distal colon (multivariate RR=2.21 [CI=1.18–4.16], P trend = 0.0001, for BMI 29 cf <21 kg/m²). Waist circumference and the waist-to-hip ratio (WHR) were not related significantly to adenoma independently of BMI, but women with both a high BMI and high WHR were at greater risk of large colon adenoma (multivariate RR=1.99, CI=0.98–4.05) than women with high BMI but relatively low WHR (multivariate RR=1.35, CI=0.61–2.97). BMI was not related to small (<1 cm) adenoma risk but physical activity had an inverse association with small adenomas in the distal colon (multivariate RR=0.68, CI=0.40–1.15, P trend = 0.03). The relationships between BMI or physical activity were considerably weaker and inconsistent for rectal adenomas. These results, in women, support an inverse association between physical activity and occurrence or progression of ademonas in the distal colon; obesity is associated with an elevated risk of large adenomas.The authors are with the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. The authors are also affiliated with the Department of Nutrition, Harvard School of Public Health, Boston, MA (Drs Giovannucci, Stampfer, and Willett), and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (Drs Colditz, Stampfer, and Willett). Address correspondence to Dr Giovannucci, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115, USA. The work was supported by research grant numbers CA 40935 and CA 55075 from the US National Institutes of Health. Dr Colditz is supported by a Faculty Research Award (FRA-398) from the American Cancer Society.     

Recall and selection bias in reporting past alcohol consumption among breast cancer cases

Recall and selection bias are well-recognized potential problems in case-control studies of alcohol and cancer, but few analyses have attempted to assess the direction and the magnitude of these potential biases. We thus examined alcohol consumption in relation to risk of breast cancer using dietary questionnaires administered both before and after the diagnosis of breast cancer in the Nurses' Health Study (United States). Among cohort members who completed a dietary questionnaire in 1986 and who were free of cancer, 616 were diagnosed with breast cancer during follow-up to December 1989. These cases and 1,277 controls (a random sample of cohort members who did not develop cancer up to 1990) then were sent another questionnaire inquiring about their diet in 1985. Four hundred and ninety-four cases (80.2 percent) and 999 controls (78.2 percent) responded to the second questionnaire. The analysis based on the prospective (1986) questionnaire demonstrated an elevated risk of breast cancer among women who drank 30 or more g of alcohol daily (about two drinks) relative to nondrinkers (odds ratio [OR]=1.55, 95 percent confidence interval [CI]=1.01–2.39). The analysis based on the retrospective questionnaire also indicated a similar but slightly attenuated elevation of risk of breast cancer among women who drank at least 30 g daily (OR=1.42, CI=0.85–2.40). In these data, bias due to selection and recall had only minor effects on reported intake of alcohol consumption.Drs Giovannucci, Stampfer, Colditz, Manson, Rosner, Speizer, and Willett are with Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Drs Colditz, Stampfer, and Willett are also with the Harvard School of Public Health, Boston, MA, USA. Dr Longnecker is with the University of California School of Public Health, Los Angeles, CA, USA. Address correspondence to Dr Giovannucci, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115, USA. The project was supported by research grant number CA 40935 and CA 55075 from the US National Institutes of Health.     

Reproductive factors and family history of breast cancer in relation to plasma estrogen and prolactin levels in postmenopausal women in the Nurses' Health Study (United States)

Parity, age at first birth, age at menarche, and a family history of breast cancer have each been associated consistently with breast cancer risk. Whether this increase in risk is mediated, at least in part, through changes in endogenous hormone levels is unclear. We conducted a cross-sectional study of the relationships between these factors and plasma hormone levels in 216 healthy postmenopausal women in the Nurses' Health Study (United States). The hormones evaluated were estradiol, percent and total free estradiol, percent and total bioavailable estradiol, estrone, estrone sulfate, and prolactin. After controlling for age, body mass index (weight/height²), and alcohol use, we observed inverse associations between estrone sulfate and parity (r=–0.15, P=0.03) and between percent bioavailable estradiol and age at first birth (r=–0.17, P=0.02). Although women with a family history of breast cancer tended to have higher estrogen levels compared with women without such history, the differences were not statistically significant. Age at menarche was not related significantly to any of the hormones. These data provide some additional evidence that the inverse relationship observed between parity and breast cancer risk may be mediated, at least in part, through decreased estrogen levels. Our data do not support a substantial influence of either family history of breast cancer or age at menarche on postmenopausal estrogen or prolactin levels.Authors are with the Channing Laboratory (Drs Hankinson, Colditz, Hunter, Manson, Willett, Stampfer, Speizer) and Divislon of Preventive Medicine (Dr Manson), Brigham and Women's Hospital and Harvard Medical School, Boston, MA (USA); Departments of Nutrition (Drs Willett, Stampfer), and Epidemiology (Drs Hankinson, Colditz, Hunter, Willett, Stampfer), Harvard School of Public Health, Boston, MA; and the Departments of Obstetrics and Gynecology and Medicine, University of Massachusetts Medical School, Worcester, MA (Dr Longcope). Address correspondence to Dr Hankinson, Channing Laboratory, 180 Longwood Ave., Boston, MA 02115, USA. This research was supported by research grants CA40356 and CA49449 from the US National Institutes of Health, Bethesda, MD. Dr Manson is a recipient of a Merk/Society for Epidemiologic Research grant award.     

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.     

Abortion and breast cancer risk in seven countries

Epidemiologic studies have been inconsistent in suggesting an association between abortion and breast cancer risk. Whether the protection provided by a full-term pregnancy also results from a short-term pregnancy or whether a prematurely terminated pregnancy could increase the risk of breast cancer is unclear. Data from a large, international collaborative study were used to evaluate the association between abortions, whether spontaneous or induced, and breast cancer risk. The data from seven countries included 3,958 breast cancer cases and 11,538 hospital controls with information on abortion history obtained through interviews. Compared with nulliparous women with no abortion (baseline), the odds ratios (OR) and 95 percent confidence intervals (CI) were: for nulliparous women with a history of prior abortion, 0,86 (CI=0.68–1.08); for parous women with no history of abortion, 0.63 (CI=0.57–0.69); for parous women with abortion before first birth, 0.82 (CI=0.69–0.97); and, for parous women with abortion only after first birth, 0.70 (CI=0.63–0.79). When restricting analysis to parous women, those with a history of abortion exhibited an elevated OR suggesting a 29 percent risk increase if the incomplete pregnancy occurred before first birth (CI=1.16–1.36) and an 11 percent risk increase for abortion only after first birth (CI=1.02–1.20) compared with women without such history. The associations observed were stronger among the youngest women. These results do not support a large overall association between abortion and breast cancer risk.Ms Michels and Drs Hsieh, Trichopoulos, and Willett are with the Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. Dr Willett is also affiliated with the Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Department of Medicine, brigham and Women's Hospital and Harvard Medical School, Boston, MA. Address correspondence to Ms Michels, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.     

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.     

Parental ages at birth in relation to a daughter's risk of breast cancer among female participants in the Framingham study (United States)

Data from the Framingham Heart Study, collected in Framingham, MA (United States) during 1948–86, were used to evaluate the relation of parental age at birth to the risk of breast cancer among daughters. After 38 years of follow-up, 149 breast cancer cases occurred among 2,662 women. All but two cases were confirmed by histologic report. The rate of breast cancer increased among daughters with increasing maternal age at birth up to the mid-30s, where the rate levelled off. A similar pattern was observed with paternal age. After adjustment for other confouding factors and paternal age, the rate ratios for breast cancer in daughters whose mothers were aged 26 to 31 years and 32 or more years at their birth, relative to women whose mothers were aged 25 years or younger, were 1.5 (95 percent confidence interval [CI]=1.0–2.4) and 1.3 (CI=0.8–2.2), respectively. However, there was no longer an association between paternal age at birth and risk of breast cancer after controlling for maternal age and other risk factors.Drs Zhang, Cupples, and Coulton are with the Department of Epidemiology and Biostatistics, School of Public Health, Boston University, Boston, MA, USA, Dr Rosenberg is with the Slone Epidemiology Unit, Boston University School of Medicine, Brookline, MA. Dr Kreger is with the Section of Preventive Medicine and Epidemiology, The Evans Memorial Department of Clinical Research, Boston University Medical Center, Boston, MA. Address correspondence to Dr Zhang, Department of Epidemiology and Biostatistics, School of Public Health, Boston University, 80 East Concord Street, Boston, MA, 02118-2394, USA.     

Age and risk factors for colon cancer (United States and Australia): Are there implications for understanding differences in case-control and cohort studies?

Data from two population-based case-control studies were used to investigate the effect of age on colon cancer risk. Dietary intake data were assessed from a study conducted in Utah (United States) between 1979 and 1983; reproductive data were assessed from a study conducted in Adelaide (Australia) between 1979 and 1980. Data from both studies were assessed for their impact on those less than 65 years of age and those 65 or more years of age. Intake of energy, fat, and protein had a greater impact on risk among older men than among younger men. Risk estimates for the upper quartile of intake relative to the lowest quartile of intake were 8.5 (95 percent confidence interval [CI]=1.7–43.0) for energy, 8.2 (CI=1.6–41.3) for protein, and 7.2 (CI=1.6–31.4) for total fat for older men, while comparable risk estimates were 2.4 (CI=0.6–9.1) for energy, 3.0 (CI=0.7–13.6) for protein, and 1.9 (CI=0.5–7.1) for total fat among younger men. Similar trends were seen for older women for energy and protein. -carotene decreased colon cancer risk among younger men (odds ratio [OR]=0.4, CI=0.1–1.2) and women (OR=0.1, CI=0.1–0.5), although not among older men (OR=1.2, CI=0.3–4.9) and women (OR=1.9, CI=0.6–64). Calcium decreased risk of colon cancer among older men (OR=0.1, CI=<0.1–0.8) and younger women (OR=0.2, CI=<0.1–0.7). Women who were diagnosed at age 65 or older and were nulliparous had a tenfold increase in colon cancer risk (CI=2.4–47.9) relative to women who had an early age at first birth. Women diagnosed with colon cancer before age 65 did not experience an increase of colon cancer risk associated with being nulliparous. These data suggest that age at diagnosis may interact with other factors to alter risk of colon cancer.This study was supported by grant number R01 CA48998 and P01 CA50305 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.     

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,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.     

Occupational physical activity and risk of cancer of the colon and rectum in New Zealand males

The association between occupational physical activity and risk of colorectal cancer by age and anatomic site was investigated in a study of 2,503 males with colorectal cancer registered with the New Zealand Cancer Registry during 1972–80. Occupational groups that involved high levels of physical activity or were predominantly sedentary were identified prior to analysis of the registry data. Relative to males in high physical activity occupations, males in sedentary occupations had an increased incidence of both cancer of the colon (relative risk [RR]=1.2; 95 percent confidence interval [CI]=1.0–1.4) and rectum (RR=1.3, CI=1.0–1.5). The RRs for sedentary workers were particularly elevated in the 35–44 and 45–54 year age-groups for colon cancer (RR=1.8 and 1.5, respectively) and in the 45–54 year age-group for rectal cancer (RR=1.5), whereas there was no increase in risk for sedentary workers in the 55–64 year age-group for either cancer site. The generalincrease in colon cancer incidence for New Zealand during the study period was reflected in the sedentary group, but there was no change in incidence among men in occupations involving high or intermediate levels of physical activity. There was no obvious pattern for the increased cancer risk for men in sedentary occupations by anatomic site. Current physiologic hypotheses for the effect of physical activity on colon cancer risk do not adequately explain an association of physical activity with risk of rectal cancer.Dr Fraser is affillated with the University of Otago, Medical School, Dunedin, New Zealand. Dr Pearce is with the Wellington School of Medicine, Wellington, New Zealand. Address correspondence to Dr Fraser, Department of Preventive and Social Medicine, University of Otago Medical School, PO Box 913, Dunedin, New Zealand.     

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.     

Screening endoscopy and risk of colorectal cancer in United States men

Objectives: The purpose of this study was to describe the effect of screening endoscopy (sigmoidoscopy or colonoscopy) on colorectal cancer incidence and mortality. Methods: We used data from a prospective cohort study of 24,744 men aged 40 to 75 years in 1986, free from cancer and colon polyps, followed until 1994. The outcomes are diagnosis of colorectal cancer and death from colorectal cancer. Results: Screening endoscopy in 1986-87 was associated with a lower risk of all colorectal cancer (multivariate relative risk [RR]=0.58, 95 percent confidence interval [CI]=0.36-0.96); cancer in the distal colon or rectum (multivariate RR=0.40, CI=0.19-0.84); Dukes stage A&B (multivariate RR=0.66, CI=0.35-1.25); and Dukes stage C&D (multivariate RR=0.50, CI=0.20-1.26) colorectal cancer; and death from colorectal cancer (multivariate RR=0.56, CI=0.20-1.60), after adjusting for age and a wide range of colon cancer risk factors. Screening endoscopy in 1988-87 appeared to provide strong protection against distal stage C&D cancers (age-adjusted RR=0.16, CI=0.02-1.23) but no protection against proximal stage C&D cancers (age-adjusted RR=0.96, CI=0.32-2.91). Conclusions: This study provides strong evidence for a protective effect of screening sigmoidoscopy on colorectal cancer incidence and mortality and supports recommendations for screening sigmoidoscopy as an approach to colon cancer prevention.     

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.     

A prospective study of tobacco use and multiple myeloma: evidence against an association

The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR]=0.9, 95 percent confidence interval [CI]=0.8–1.2) or former (RR=1.0, CI=0.8–1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR=1.0, CI=0.4–2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR=1.2, CI=0.9–1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occuring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma.Epidemiology and Biometry Program, Division of Cancer Etiology, National Cancer Institute. Westat, Inc. Rockville, MD. National Cancer Institute, 6130 Executive Blvd, Room 418, Rockville, MD 20892, USA.     

Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States)

Objectives: The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics. Methods: Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models. Results: 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9–1.0); prostate (RR = 1.0, 95% CI = 0.9–1.1); colon (RR = 0.9, 95% CI = 0.7–1.2); or lung (RR = 0.9, 95% CI = 0.7–1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7–1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8–1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7–1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6–1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3–0.8). Conclusions: The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.     

Folate,methionine, alcohol,and colorectal cancer in a prospective study of women in the United States

Objective: We investigated the associations of folate, methionine, and alcohol intake, as well as combinations of these factors, with risk of colorectal cancer (CRC). Methods: We assessed diet using a 62-item food-frequency questionnaire among 45,264 women in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study. After an average of 8.5 years of follow-up, 490 cases of CRC were identified. Results: Dietary folate showed only a slight inverse association with the risk of CRC (RR = 0.86, 95% CI 0.65–1.13 for high vs. low quintile, p for trend = 0.14), and the association for total folate was null. Consuming more than two servings of alcohol per day was only slightly associated with CRC in this cohort (RR = 1.16, 95% CI 0.63–2.14). Combinations of high alcohol and low total folate did not result in a higher risk of CRC. There was no association between methionine and colorectal cancer. Conclusions: This study shows limited association between alcohol intake and CRC. The non-association of total folate and methionine with CRC, and the null results from the combined folate and alcohol analyses, suggest that what effect alcohol may have on CRC is unrelated to the methyl-group metabolism pathway.     

Incidence of selected cancers in Swedish railway workers, 1961–79

Among all Swedish men, 20 to 64 years of age and employed in 1960, railway workers were selected and compared with the population at large, concerning the incidence of leukemia, lymphoma, tumors of the brain, breast, and the pituitary gland. The study was a re-analysis of the 1961–79 incidence data previously showing no increase in risk for leukemia and brain tumors for railway workers. In the present study, follow-up was divided into two 10-year periods, and elevated relative risks (RR) were found for the first decade. For the first decade, engine drivers and conductors combined had an RR of chronic lymphocytic leukemia, acute myeloid leukemia, and lymphoma of 1.9 (95 percent confidence interval [CI]=0.9–4.0), 1.4 (CI=0.4–4.3), and 1.0 (CI=0.5–1.9), respectively. For all brain tumors, the RR was 1.2 (CI=0.8–1.9), with a higher risk estimate for those below age 30 (RR=12.2, CI=2.8–52.5). Three cases of breast cancer and nine cases of tumors of the pituitary gland occurred among engine drivers and conductors, corresponding to RRs of 4.9 (CI=1.6–11.8) and 3.2 (CI=1.6–6.2), respectively. Work on trains entails extremely high exposure to low frequency magnetic fields (EMF). The results give some support to the hypothesis of an association between EMF and certain types of cancers. The outcome for the pituitary gland, being a focal point of hormonal regulation, suggests a hormonal link.The project was funded partially by the National Board of Occupational Safety and Health.     

Calcium,vitamin D,dairy products,and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States)

Objective: Calcium, vitamin D, and dairy product intake may reduce the risk of colorectal cancer. We therefore examined the association between these factors and risk of colorectal cancer in a large prospective cohort of United States men and women. Methods: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 1992–93. After excluding participants with a history of cancer or incomplete dietary information, 60,866 men and 66,883 women remained for analysis. During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women, respectively. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models. Results: Total calcium intake (from diet and supplements) was associated with marginally lower colorectal cancer risk in men and women (RR = 0.87, 95% CI 0.67–1.12, highest vs lowest quintiles, p trend = 0.02). The association was strongest for calcium from supplements (RR = 0.69, 95% CI 0.49–0.96 for 500 mg/day vs none). Total vitamin D intake (from diet and multivitamins) was also inversely associated with risk of colorectal cancer, particularly among men (RR = 0.71, 95% CI 0.51–0.98, p trend = 0.02). Dairy product intake was not related to overall risk. Conclusions: Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer. Vitamin D was associated with reduced risk of colorectal cancer only in men.     

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.