Body Mass Index, Physical Activity, and Bladder Cancer in a Large Prospective Study

Increased body size and lack of physical activity are associated with increased risk of several cancers, but the relations of body mass index (BMI) and physical activity to bladder cancer are poorly understood. We investigated the associations between BMI, physical activity, and bladder cancer in the NIH-AARP Diet and Health Study, a prospective cohort of 471,760 U.S. men and women, followed from 1995 to 2003. During 3,404,642 person-years of follow-up, we documented 1,719 incident cases of bladder cancer. Compared with normal weight, obesity was associated with an up to 28% increased risk for bladder cancer. The multivariate relative risks of bladder cancer for BMI values of 18.5 to 24.9 (reference), 25.0 to 29.9, 30.0 to 34.9, and ≥35 kg/m2 were 1.0, 1.15, 1.22, and 1.28 (95% confidence interval, 1.02-1.61; Ptrend = 0.028). The association between BMI and bladder cancer was consistent among subgroups defined by gender, education, smoking status, and other potential effect modifiers. In contrast, physical activity showed no statistically significant relation with bladder cancer. After multivariate adjustment, including BMI, the relative risks of bladder cancer for increasing frequency of physical activity [0 (reference), <1, 1-2, 3-4, and ≥5 times a week] were 1.0, 0.85, 0.89, 0.91, and 0.87 (95% confidence interval, 0.74-1.02; Ptrend = 0.358), respectively. In conclusion, these findings provide support for a modest adverse effect of adiposity on risk for bladder cancer. In contrast, our results do not suggest a relation between physical activity and bladder cancer.

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title: Mechanisms of Disease: the epidemiology of bladder cancer
abstract: Mortality from bladder cancer has shown downward trends over the last 2 decades in several western European countries (albeit 10–15 years later than similar trends in the US), but is still increasing in some eastern European countries. Tobacco smoking and occupational exposure to aromatic amines are the two major established environmental risk factors for bladder cancer. Controlling exposure to these factors has been an important contributor to the reduction in bladder cancer mortality, particularly among men. Diet could influence bladder carcinogenesis, as many compounds contained in foods—and their metabolites—are excreted through the urinary tract. Fruit and vegetable consumption was inversely related with bladder cancer in many studies, but no consistent association has emerged between intake of related micronutrients and reduced risk of bladder cancer. Other widely investigated lifestyle habits are probably not associated with risk of developing bladder cancer (e.g. coffee consumption, artificial sweetener use, hair dyes) or are difficult to assess (e.g. fluid intake). Infections and stones in the urinary tract might cause chronic irritation of the bladder epithelium, and thus increase bladder cancer risk. First-degree relatives of bladder cancer patients have a 50–100% increased relative risk of developing the disease, a risk that could be even higher when the proband is diagnosed at an early age.

title: Obesity and cancer risk among white and black United States veterans
abstract: Obesity has been linked to excess risk for many cancers, but the evidence remains tenuous for some types. Although the prevalence of obesity varies by race, few studies of obesity-related cancer risk have included non-white subjects.  In a large cohort of male US veterans (3,668,486 whites; 832,214 blacks) hospitalized with a diagnosis of obesity between 1969 and 1996, we examined risk for all major cancer sites and subsites. Person-years accrued from the date of first obesity diagnosis until the occurrence of a first cancer, death, or the end of the observation period (September 30, 1996). We calculated age- and calendar-year adjusted relative risks (RR) and 95% confidence intervals (CI) for cancer among white and black veterans, comparing obese men to men hospitalized for other reasons, with obesity status as time-dependent. For selected cancers, we performed additional analyses stratified by specific medical conditions related to both obesity and risk of those cancers. To determine whether obesity-related cancer risks differed significantly between white and black men, we evaluated heterogeneity of risk for each cancer site.  Among white veterans, risk was significantly elevated for several cancers, including cancers of the lower esophagus, gastric cardia, small intestine, colon, rectum, gallbladder and ampulla of vater, male breast, prostate, bladder, thyroid, and connective tissue, and for malignant melanoma, multiple myeloma, chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML). Excess risks initially observed for cancers of the liver and pancreas persisted among men without a history of diabetes or alcoholism. Among black veterans, risks were significantly elevated for cancers of the colon, extrahepatic bile ducts, prostate, thyroid, and for malignant melanoma, multiple myeloma, CLL and AML.  Obese men are at increased risk for several major cancers as well as a number of uncommon malignancies, a pattern generally similar for white and black men. Due to the increasing prevalence of obesity and overweight worldwide, it is important to clarify the impact of excess body weight on cancer and to elucidate the mechanisms involved.

title: Obesity and cancer risk: a Danish record-linkage study.
abstract: A cohort of 43,965 obese persons was accrued on the basis of discharge registrations from Danish hospitals, and incidence of cancer in the cohort was compared to that in the Danish population as a whole using indirect standardisation for age and period. Increased incidence was observed for cancer of the uterine corpus independently of age [114 cases, relative risk (RR) = 2.0, confidence interval 1.6-2.4], and for breast cancer in women above the age of 70 (133 cases, RR = 1.2). These findings are consistent with previous studies. In younger women, breast cancer occurred less frequently and ovarian cancer occurred more frequently than expected. Increased incidence was observed for cancers of the oesophagus (26 cases, RR = 1.9) and the liver (58 cases, RR = 1.9), probably reflecting an increased prevalence of excessive alcohol consumption in the cohort. Increased incidence was furthermore observed for cancers of the pancreas (101 cases, RR = 1.7), the prostate (96 cases, RR = 1.3) and the colon (195 cases, RR = 1.2), which may indicate the existence of risk factors which are common to obesity and to these cancers, for example, dietary habits. Kidney cancer was increased in women only. Overall, the incidence of cancer was increased by 16% in the cohort. The results were essentially unchanged by restriction to the subcohort of 8207 persons in whom obesity was the primary discharge diagnosis, and were also similar in the first year of follow-up after hospital discharge. Selection bias is, therefore, not likely to have influenced the results.

title: A prospective study of obesity and cancer risk (Sweden)
abstract: We evaluated the relation between obesity and the risks for various forms of cancer.
 In a population-based cohort of 28,129 hospital patients (8165 men, 19,964 women) with any discharge diagnosis of obesity (9557 only diagnosis, 5266 primary, 13,306 secondary) during 1965–1993, cancer incidence was ascertained through 1993 by record linkage to the nationwide Swedish Cancer Registry. Cancer risk was estimated using the standardized incidence ratio (SIR, with 95% confidence interval), which is the ratio of the observed number of cancers to that expected.
 Overall, a 33% excess incidence of cancer was seen in obese persons, 25% in men and 37% in women. Significant risk elevations were observed for cancers of the small intestine (SIR = 2.8; 95% CI 1.6–4.5), colon (1.3; 1.1–1.5), gallbladder (1.6; 1.1–2.3), pancreas (1.5; 1.1–1.9), larynx (2.1; 1.1–3.5), renal parenchyma (2.3; 1.8–2.8), bladder (1.2; 1.0–1.6), cervix uteri (1.4; 1.1–1.9), endometrium (2.9; 2.5–3.4), ovary (1.2; 1.1–1.5), brain (1.5; 1.2–1.9), and connective tissue (1.9; 1.1–3.0), and for lymphomas (1.4; 1.0–1.7), with higher risk observed for Hodgkin's disease only in men (3.3; 1.4–6.5) and for non-Hodgkin's lymphoma only in women (1.6; 1.2–2.1). The association of obesity with risk of breast, prostate and pancreas cancers was modified by age.
 Obesity is associated with more forms of cancer than previously reported.

title: Early precursors of urogenital cancers in former college men.
abstract: Physical and social characteristics recorded at college physical examination or reported at subsequent alumni questionnaire in 1962 or 1966 by 47,271 male former students from Harvard University and the University of Pennsylvania were reviewed for their relationship to risk for cancers of the kidney, bladder, prostate and testis. The records of 213 subjects who died with 1 of these cancers in a 16-50 year followup period and of 280 subjects who reported such a cancer by mail questionnaire in 1976 or 1977 were compared with those of 1,972 matched classmates who were known to be alive and cancer-free at the time subjects with cancer had died or were diagnosed. Students with a record of proteinuria at college physical examination experienced increased risk of kidney cancer. Higher levels of body weight during college were associated with elevated risks of kidney and bladder cancers; however, increased weight in 1962/1966 related only to kidney cancer. A history of cigarette smoking as reported by questionnaire in 1962/1966 predicted increased occurrence of bladder cancer. Students with a history of tonsillectomy at college entrance experienced increased risk of prostate cancer, and those who reported cancer history in 1 or both parents were at increased risk for testicular cancer. These and other findings are presented as clues deserving further exploration for any etiological significance they may hold for the cancer sites studied.

title: Obesity and overweight in relation to organ-specific cancer mortality in London (UK): findings from the original Whitehall study
abstract: To examine the relation of obesity and overweight with organ-specific cancer mortality.In the Whitehall prospective cohort study of London-based government employees, 18 403 middle-age men participated in a medical examination between 1967 and 1970. Subjects were followed up for cause-specific mortality for up to 35 y (median: interquartile range (25th–75th centile); 28.1 y: 18.6–33.8).RESULTS:There were over 3000 cancer deaths in this cohort. There was a raised risk of mortality from carcinoma of the rectum, bladder, colon, and liver, and for lymphoma in obese or overweight men following adjustment for range of covariates, which included socioeconomic position and physical activity. These relationships held after exclusion of deaths occurring in the first 20 y of follow-up.Avoidance of obesity and overweight in adult life may reduce the risk of developing some cancers.

title: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults.
abstract: The influence of excess body weight on the risk of death from cancer has not been fully characterized.



In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population.



The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women.



Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.

title: Prospective study of body mass index, height, physical activity and incidence of bladder cancer in US men and women
abstract: We evaluated prospectively the association between body mass index (BMI), height, recreational physical activity and the risk of bladder cancer among US adults. Data were used from 2 ongoing cohorts, the Health Professionals Follow‐up Study and the Nurses' Health Study, with 3,542,012 years of follow‐up and 866 incident bladder cancer cases (men = 507; women = 359) for the anthropometric analysis and 1,890,476 years of follow‐up and 706 incident bladder cancer cases (men = 502; women = 204) for the physical activity analysis. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between BMI, height, physical activity and bladder cancer risk adjusting for age, pack‐years of cigarette smoking and current smoking. Estimates from each cohort were pooled using a random‐effects model. We observed no association between baseline BMI and bladder cancer risk, even when we compared a BMI of ≥30 kg/m2 to a BMI of 18–22.9 kg/m2 [pooled multivariate (MV) RR, 1.16; 95% CI: 0.89–1.52]. A weak, but statistically significant, association was observed for the same comparison after excluding bladder cancer cases diagnosed within the first 4 years of follow‐up (pooled MV RR, 1.33; 95% CI: 1.01–1.76). Height was not related to bladder cancer risk (pooled MV RR, 0.82; 95% CI: 0.65–1.03, top vs. bottom quintile). Total recreational physical activity also was not associated with the risk of bladder cancer (pooled MV RR, 0.97; 95% CI: 0.77–1.24, top vs. bottom quintile). Our findings do not support a role for BMI, height or physical activity in bladder carcinogenesis.

title: Variations in mortality by weight among 750,000 men and women.
abstract: This paper is based on a portion of a long-term prospective study conducted by the American Cancer Society over the period 1959–1972. It describes the mortality experience according to variations in weight among 750,000 men and women drawn from the general population. The lowest mortality was found among those close to average weight and those 10–20% below average weight. Mortality among men and women 30–40% heavier than average was nearly 50% higher than among those of average weight; among those more than 40% heavier than average it was nearly 90% higher than among those of average weight. Coronary heart disease was the major factor in the higher mortality of overweights, being 55% higher among those 30–40% heavier than average, and about 100% higher among those more than 40% overweight. Cancer mortality was elevated only among those 40% or more overweight; cancer of the colon and rectum was the principal site of excess cancer mortality among men, while cancer of the gall bladder and biliary passages, breast, cervix, endometrium, uterus and ovary were the major sites of excess mortality among women. Mortality from diabetes was particularly high among overweights, especially women. The mortality findings of this study match closely those of the Build and Blood Pressure Study 1959 based on the experience of 412 million insured persons.

title: Obesity and incidence of cancer: a large cohort study of over 145 000 adults in Austria
abstract: We investigated the relation of overweight and obesity with cancer in a population-based cohort of more than 145 000 Austrian adults over an average of 9.9 years. Incident cancers (n=6241) were identified through the state cancer registry. Using Cox proportional-hazards models adjusted for smoking and occupation, increases in relative body weight in men were associated with colon cancer (hazard rate (HR) ratio 2.48; 95% confidence interval (CI): 1.15, 5.39 for body mass index (BMI) ⩾35 kg m−2) and pancreatic cancer (HR 2.34, 95% CI: 1.17, 4.66 for BMI>30 kg m−2) compared to participants with normal weight (BMI 18.5–24.9 kg m−2). In women, there was a weak positive association between increasing BMI and all cancers combined, and strong associations with non-Hodgkin's lymphomas (HR 2.86, 95% CI: 1.49, 5.49 for BMI⩾30 kg m−2) and cancers of the uterine corpus (HR 3.93, 95% CI: 2.35, 6.56 for BMI⩾35 kg m−2). Incidence of breast cancer was positively associated with high BMI only after age 65 years. These findings provide further evidence that overweight is associated with the incidence of several types of cancer.

title: Reproductive factors, exogenous hormone use and bladder cancer risk in a prospective study
abstract: Sex is a consistent predictor of bladder cancer: men experience 2–4‐fold higher age‐adjusted rates than women in the U.S. and Europe. The objective of this study was to examine whether hormone‐related factors are associated with bladder cancer in women. We examined parity, age at menarche, age at first birth, age at menopause, oral contraceptive use and menopausal hormone therapy (HT) use and bladder cancer risk in the Breast Cancer Detection Demonstration Project Follow‐Up Study. Endpoint and exposure information was collected on 54,308 women, using annual telephone interviews (1980–86) and 3 mailed, self‐administered questionnaires (1987–98). During an average follow‐up time of 15.3 years, 167 cases of bladder cancer were identified. Univariate and adjusted rate ratios (RRs) were estimated using Poisson regression. Parity, age at menarche, age at first birth, age at menopause, and oral contraceptive use were not associated with bladder cancer risk. The majority of menopausal women who took HT used estrogen therapy (ET). Postmenopausal women with less than 4 years, 4–9 years, 10–19 years and 20 or more years of ET use had RRs of 1.55 (95% CI = 0.96–2.51), 1.00 (95% CI = 0.49–2.04), 1.23 (95% CI = 0.62–2.43) and 0.57 (95% CI = 0.14–2.34), respectively, compared with nonusers (p = 0.50). Findings from this study are not consistent with the hypothesis that hormone‐related factors in women are associated with bladder cancer.

title: Association of obesity and cancer risk in Canada.
abstract: The authors conducted a population-based, case-control study of 21,022 incident cases of 19 types of cancer and 5,039 controls aged 20-76 years during 1994-1997 to examine the association between obesity and the risks of various cancers. Compared with people with a body mass index of less than 25 kg/m(2), obese (body mass index of > or = 30 kg/m(2)) men and women had an increased risk of overall cancer (multivariable adjusted odds ratio = 1.34, 95% confidence interval (CI): 1.22, 1.48), non-Hodgkin's lymphoma (odds ratio = 1.46, 95% CI: 1.24, 1.72), leukemia (odds ratio = 1.61, 95% CI: 1.32, 1.96), multiple myeloma (odds ratio = 2.06, 95% CI: 1.46, 2.89), and cancers of the kidney (odds ratio = 2.74, 95% CI: 2.30, 3.25), colon (odds ratio = 1.93, 95% CI: 1.61, 2.31), rectum (odds ratio = 1.65, 95% CI: 1.36, 2.00), pancreas (odds ratio = 1.51, 95% CI: 1.19, 1.92), breast (in postmenopausal women) (odds ratio = 1.66, 95% CI: 1.33, 2.06), ovary (odds ratio = 1.95, 95% CI: 1.44, 2.64), and prostate (odds ratio = 1.27, 95% CI: 1.09, 1.47). Overall, excess body mass accounted for 7.7% of all cancers in Canada-9.7% in men and 5.9% in women. This study provides further evidence that obesity increases the risk of overall cancer, non-Hodgkin's lymphoma, leukemia, multiple myeloma, and cancers of the kidney, colon, rectum, breast (in postmenopausal women), pancreas, ovary, and prostate.

title: Smoking and other risk factors for bladder cancer in women.
abstract: Bladder cancer is three to five times more frequent in men than in women, and hence only a few studies have focused only on females.



A case-control study was conducted between 1985 and 1992 in two areas of northern Italy, and included 110 women with histologically confirmed bladder cancer and 298 controls, admitted to the same network of hospitals of cases for acute, non-neoplastic, non-urinary or genital tract diseases. Multivariate odds ratios (ORs) were computed using unconditional multiple logistic regression.



Compared to never smokers, current smokers (OR = 2.87) had significantly elevated risks of bladder cancer. High intake of vegetables was inversely related to the disease (OR = 0.32), while history of occupation in chemical, dyes/paints or pharmaceutical industry (OR = 3.01) was directly associated to risk of bladder cancer. The OR was 3.29 for ever use of menopause hormone replacement therapy.



This study confirms that cigarette smoking is the prominent risk factor for bladder cancer in women as in men, with similar relations in both sexes. It also confirms that selected occupational factors are related to bladder cancer risk, and supports a favourable role of vegetables. The apparent relation with hormone replacement therapy in menopause needs interpretation and further investigation.

title: Cancer of the urinary bladder in blacks and whites: A case–control study
abstract: Racial differences in the risk of cancer of the urinary bladder associated with cigarette smoking and alcohol consumption were examined in a study of 1663 cases (1534 whites and 129 blacks) and 4930 controls matched 3:1 by sex, race, and age to the cases. Significant increases in cancer risk associated with cigarette smoking were observed in whites and blacks; however, the dose‐response patterns appeared to differ by race. in whites, statistically significant elevations of threefold and higher were observed in the odds ratios at all smoking levels above 20 pack‐years, whereas in blacks, the corresponding point estimates did not increase significantly until > 60 pack‐years of smoking. Although these risk patterns are compatible with the higher incidence of bladder cancer in white men, the sample of blacks was small, and tests of significance were only suggestive of higher risks for whites at specific amounts of smoking (P < 0.15). Effects of alcohol consumption were inconsistent, and there was no detectable synergism between smoking and drinking. Additional study of race‐specific risk factors and tobacco metabolism will be needed to determine the true nature of the apparent racial differences in the risk of urinary bladder cancer associated with cigarette smoking.

title: Diet in the epidemiology of bladder cancer in western New York.
abstract: We present the dietary epidemiology of bladder cancer while controlling for a number of lifestyle and environmental risk factors in a study of 351 white male cases with histologically confirmed transitional cell carcinoma of the bladder and 855 white male controls selected from Erie, Niagara, and Monroe counties of western New York from 1979 to 1985. Usual diet was estimated by comprehensive interviews with use of a detailed food frequency questionnaire. An increased risk of bladder cancer was associated with higher kilocalorie intake, but only among those under 65 years of age, with the strongest pattern associated with fat intake. Further analyses of fat, carbohydrates, and protein, with adjustment for total kilocalories, resulted in a positive association of risk with fat intake and a decreasing risk with higher protein intake. Of the vitamins, carotenoid consumption appeared to decrease risk with increased consumption for those under 65 years of age. No significant differences between cases and controls were seen for intake of calcium, retinol, thiamin, riboflavin, niacin, vitamin C, vitamin D, and vitamin E. After adjustment for kilocalories and other confounders, higher intake of dietary sodium was associated with increased risk among both age groups, and the trends were statistically significant. The importance of diet in the etiology of bladder cancer is suggested by our findings.

title: Occupational physical activity, socioeconomic status, and risks of 15 cancer sites in Turkey
abstract: A multiple-site case-control study of 15 cancers (stomach; colon; rectum; larynx; lung; melanoma; skin; female breast; male breast; cervix; ovary; uterus; prostate; testis; and bladder) was conducted to evaluate their association with occupational physical activity and socioeconomic status (SES). A hospital-based study population (3,486 male cases and 379 female cases, and 2,127 male and 244 female controls) was established in an oncological treatment center in Istanbul, Turkey, from 1979–84. Assessment of physical activity and SES was based on job titles held by the study subjects. Two measures of physical activity were developed based on energy expenditure and ‘sitting time’ during working hours. Observed risks were adjusted for age, smoking, and SES. Elevated risks were observed among workers who held sedentary jobs for cancers of the colon (odds ratio [OR=1.6), rectum (OR=1.3), melanoma (OR=1.9), male breast (OR=1.4), prostate (OR=5.0), and ovary (OR=2.0). Cancers of the cervix and uterus showed significantly decreasing risks with decreased activity. Risks of cancers of the colon, rectum, larynx, ovary, and melanoma were enhanced after risks for physical activity indices were adjusted for SES, while the associations between physical activity and cancers of the prostate, cervix, and uterus were weakened after SES adjustment. Risks of melanoma rose significantly with both activity indices after SES adjustment. The results of this study support previously reported associations between physical activity and cancers of the colon and rectum observed in developed countries, and provide additional evidence for cancers of the larynx, prostate, cervix, uterus, and melanoma, and point out the importance of SES in evaluation of physical activity and cancers of the colon, rectum, larynx, prostate, breast, cervix, and melanoma in developing countries.

title: Physical activity on the job and cancer in Missouri.
abstract: We conducted a series of case-control studies to investigate the risks of 16 cancer types in relation to occupational physical activity. These studies were based on Missouri Cancer Registry data for 17,147 White male cancer patients registered between 1984 and 1989. Colon cancer risk was increased for both the moderate (odds ratio (OR) = 1.1; 95% confidence interval (CI) = 1.0, 1.3) and low (OR = 1.2; 95% CI = 1.0, 1.5) activity levels. Similar elevations were observed for prostate cancer at the moderate (OR = 1.1; 95% CI = 1.0, 1.3) and low (OR = 1.5; 95% CI = 1.2, 1.8) levels of activity, and for cancer of the testis at the low activity level (OR = 2.2; 95% CI = 1.3, 3.7). An opposite trend (p less than 0.01) was noted for lung cancer, which showed decreased risk at the moderate (OR = 0.9; 95% CI = 0.8, 1.0) and low (OR = 0.8; 95% CI = 0.6, 0.9) activity levels. These associations suggest that further study of the relationship between physical activity and site-specific cancer risk is warranted.

title: Physical activity and incidence of cancer in diverse populations: a preliminary report.
abstract: Physical activity relates inversely to mcidence ofcoronary heart disease and delays allcause mortality, but its influences on cancer are less clear, perhaps because cancer is a matrix of diseases differing in etiology, site, timing, symptoms, and course. Data on four populations studied primarily for hypertensiveatherosclerotic disease have been reviewed further for incidence of cancer in relation to levels of physical activity on the job and in leisure time. The present report compares and contrasts these four studies with a view to assessing significant variations in their findings on exercise and cancer.

title: Occupational exposure to air pollution and cancer risk among Danish urban mail carriers
abstract: objective was to study the risk of cancer associated with exposure to air pollution among mail carriers. We carried out a retrospective cohort study of 17,233 persons who had been mail carriers during the period 1898–1996. Data on employment was obtained from company files. Data on cancer was obtained from the Danish Cancer Registry.ResultsMale mail carriers employed for more than 3 months had a low incidence of cancer, standardised incidence ratio (SIR) 0.92. For cancers related to air pollution the risk estimates were 0.96 for lung cancer, 0.91 for laryngeal cancer and 0.98 for bladder cancer. A significant low risk for cancer of the oesophagus (SIR 0.50), kidney (SIR 0.73), prostate (SIR 0.81) and skin (melanoma) (SIR 0.87) was seen. Among female mail carriers the risk pattern showed a significant excess of cancer of the cervix uteri (SIR 2.24).ConclusionIn our study of mail carriers who had spent most of their day doing physical hard work outside in the general air pollution we saw no excess in cancers related to air pollution compared with the general population of Copenhagen. This might be due to the protective effect of physical activity.

title: A prospective analysis of physical activity and cancer.
abstract: Previous studies have suggested that increased physical activity may be protective against colon cancer. Most of these studies measured activity indirectly. The present study evaluated several direct measurements of physical activity and also resting heart rate as determined from an electrocardiogram. Increased activity was consistently associated with a decreased relative risk of colon cancer for each measure of activity. The colon cancer relative risk estimates for the middle and upper tertiles of a physical activity index (compared with the lower tertile) were 0.56 (95% confidence interval (CI) 0.39-0.80) and 0.71 (95% CI 0.51-0.99), respectively. Relative risk of colon cancer associated with moderate or heavy activity at home/recreation (compared with mostly sitting) was 0.66 (95% CI 0.49-0.88). A similar comparison of activity at work resulted in a relative risk estimate of 0.72 (95% CI 0.52-1.00). Relative risk of colon cancer increased significantly (p = 0.027) with increasing resting heart rate. Relative risks associated with physical activity were also evaluated for cancers of the stomach, rectum, lung, prostate, and urinary bladder. An increased relative risk of stomach cancer was associated with several measures of increased activity, but these results are preliminary and additional research is necessary to further evaluate this finding.

title: Occupation and bladder cancer: a cohort study in Sweden
abstract: In a follow-up study of occupational exposures and bladder cancer, an increased risk was observed after an adjustment for smoking, for physicians, administrators and managers, clerical workers and sales agents among men and assistant nurses among women. For physicians, the reason may be early diagnosis; for the other groups a sedentary type of work may have a role in bladder cancer aetiology.

title: Physical activity and risk of cancer in middle-aged men
abstract: A prospective study was carried out to examine the relationship between physical activity and incidence of cancers in 7588 men aged 40–59 years with full data on physical activity and without cancer at screening. Physical activity at screening was classified as none/occasional, light, moderate, moderately-vigorous or vigorous. Cancer incidence data were obtained from death certificates, the national Cancer Registration Scheme and self-reporting on follow-up questionnaires of doctor-diagnosed cancer. Cancer (excluding skin cancers) developed in 969 men during mean follow-up of 18.8 years. After adjustment for age, smoking, body mass index, alcohol intake and social class, the risk of total cancers was significantly reduced only in men reporting moderately-vigorous or vigorous activity; no benefit seen at lesser levels. Sporting activity was essential to achieve significant benefit and was associated with a significant dose-response reduction in risk of prostate cancer and upper digestive and stomach cancer. Sporting (vigorous) activity was associated with a significant increase in bladder cancer. No association was seen with colo-rectal cancer. Non-sporting recreational activity showed no association with cancer. Physical activity in middle-aged men is associated with reduced risk of total cancers, prostate cancer, upper digestive and stomach cancer. Moderately-vigorous or vigorous levels involving sporting activities are required to achieve such benefit.

title: Reliability and validity of a brief physical activity assessment for use by family doctors
abstract: To evaluate the reliability and validity of a brief physical activity assessment tool suitable for doctors to use to identify inactive patients in the primary care setting.  Volunteer family doctors (n  =  8) screened consenting patients (n  =  75) for physical activity participation using a brief physical activity assessment tool. Inter-rater reliability was assessed within one week (n  =  71). Validity was assessed against an objective physical activity monitor (computer science and applications accelerometer; n  =  42).  The brief physical activity assessment tool produced repeatable estimates of “sufficient total physical activity”, correctly classifying over 76% of cases (κ 0.53, 95% confidence interval (CI) 0.33 to 0.72). The validity coefficient was reasonable (κ 0.40, 95% CI 0.12 to 0.69), with good percentage agreement (71%).  The brief physical activity assessment tool is a reliable instrument, with validity similar to that of more detailed self report measures of physical activity. It is a tool that can be used efficiently in routine primary healthcare services to identify insufficiently active patients who may need physical activity advice.

title: Physical activity recommendations and decreased risk of mortality.
abstract: Whether national physical activity recommendations are related to mortality benefit is incompletely understood.



We prospectively examined physical activity guidelines in relation to mortality among 252,925 women and men aged 50 to 71 years in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Physical activity was assessed using 2 self-administered baseline questionnaires.



During 1,265,347 person-years of follow-up, 7,900 participants died. Compared with being inactive, achievement of activity levels that approximate the recommendations for moderate activity (at least 30 minutes on most days of the week) or vigorous exercise (at least 20 minutes 3 times per week) was associated with a 27% (relative risk [RR], 0.73; 95% confidence interval [CI], 0.68-0.78) and 32% (RR, 0.68; 95% CI, 0.64-0.73) decreased mortality risk, respectively. Physical activity reflective of meeting both recommendations was related to substantially decreased mortality risk overall (RR, 0.50; 95% CI, 0.46-0.54) and in subgroups, including smokers (RR, 0.48; 95% CI, 0.44-0.53) and nonsmokers (RR, 0.54; 95% CI, 0.45-0.64), normal weight (RR, 0.45; 95% CI, 0.39-0.52) and overweight or obese individuals (RR, 0.48; 95% CI, 0.44-0.54), and those with 2 h/d (RR, 0.53; 95% CI, 0.44-0.63) and more than 2 h/d of television or video watching (RR, 0.50; 95% CI, 0.45-0.55). Engaging in physical activity at less than recommended levels was also related to reduced mortality risk (RR, 0.81; 95% CI, 0.76-0.86).



Following physical activity guidelines is associated with lower risk of death. Mortality benefit may also be achieved by engaging in less than recommended activity levels.

title: Gender, racial and age differences in bladder cancer incidence and mortality.
abstract: Bladder cancer is the fourth most commonly diagnosed cancer in men and the eighth most common in women in the United States. While clinicians who diagnose and treat the disease recognize that bladder cancer has a unique demographic profile, the influence of such factors as age, gender and race on incidence, prognosis, and survival of patients is poorly understood, and has not been the subject of intense investigation. Both through analysis of the population-based databases of bladder cancer in the United States and Europe, as well as epidemiological studies, some of the effects of gender, race and age on this disease have begun to be explained. In this manuscript we review the current literature and epidemiological studies on the affects of gender, race and age on incidence and mortality of bladder cancer.

title: Characterization of insulin-like growth factor I binding sites in human bladder cancer cell lines
abstract: role of insulin-like growth factor I (IGF-I) in the growth and development of bladder cancer cells was investigated using cultured human cell lines representing differentiated (RT-4, 5637) or undifferentiated (T-24, J-82, TCC-SUP) transitional cell carcinoma (TCC). In the presence of 2% serum, IGF-I significantly stimulated the growth of all cell lines. The proliferation of T-24, 5637, and RT-4 cells was more sensitive to IGF-I than that of J-82 and TCC-SUP cells. [125I]IGF-I binding to 5637 and J-82 cells was significantly higher than that to T-24 and TCC-SUP cells (P<0.001). RT-4 cells possessed the lowest binding capacity among the cell lines tested. Scatchard analysis of [125I]IGF-I binding to four of the five cell lines indicated a single binding site for IGF-I, with apparent dissociation constants (Kd) of 1.27, 1.18, 1.34, and 1.39 nmol/l for TCC-SUP, J-82, 5637, and T-24, respectively. Therefore, the difference observed in [125I]IGF-I binding among the bladder cancer cell lines was attributed to the difference of IGF-I binding sites and not to a change in receptor binding affinity. Cross-linking studies supported the suggestion that [125I]IGF-I was bound to a receptor on these cells. The results indicate that cultured human bladder cancer cells contain functional IGF-I receptors. A differentiated cell line, RT-4, possesses significantly fewer IGF-I receptors than other cell lines. This suggests that the overexpression of IGF-I receptor may reflect the malignant potential of bladder cancer cells.

title: Plasma levels of insulin-like growth factor-1 and binding protein-3, and their association with bladder cancer risk.
abstract: Because insulin-like growth factors (IGFs) and their binding proteins have been implicated in the development of prostate, breast, colon and lung cancer, we examined the role of IGF-1 and IGF binding protein-3 levels in bladder cancer risk.



We used an enzyme-linked immunosorbent assay to compare plasma levels of IGF-1 and IGF binding protein-3 in 154 patients with bladder cancer and 154 controls from an ongoing case-control study.



Mean IGF-1 was significantly higher in cases than in controls (175.8 versus 153.2 ng./ml., p <0.01). Mean IGF binding protein-3 was significantly lower in cases than in controls (2,632.9 versus 3,056.6 ng./ml., p <0.01). The highest quartile plasma levels of IGF-1 were associated with an increased risk of bladder cancer (OR 3.10, 95% CI 1.43 to 6.70) and the highest quartile plasma levels of IGF binding protein-3 were associated with a reduced risk of bladder cancer (OR 0.38, 95% CI 0.19 to 0.78). The effects were more striking when IGF-1 and IGF binding protein-3 levels were analyzed together. In addition, a higher molar ratio of IGF-1-to-IGF binding protein-3 was associated with an increased risk of bladder cancer (OR 4.30, 95% CI 1.99 to 9.28). Dose-response relationships were evident when subjects were categorized into quartiles by the values of IGF-1, IGF binding protein-3 and the molar ratio in controls.



To our knowledge this is the first study to suggest that patients with bladder cancer have higher plasma levels of IGF-1 and lower levels of IGF binding protein-3 than controls. Thus, measuring plasma IGF-1 and IGF binding protein-3 may be useful for assessing bladder cancer risk.

title: Diabetes mellitus and risk of bladder cancer: a meta-analysis
abstract: evidence indicates that individuals with diabetes mellitus have an increased risk of several cancers. We performed a systematic review with meta-analysis to evaluate the association between diabetes and risk of bladder cancer.MethodsPertinent studies were identified by searching MEDLINE (from January 1966 to July 2006) and by reviewing the reference lists of retrieved articles. We included case–control and cohort studies reporting relative risk (RR) estimates with 95% CIs (or data to calculate them) of bladder cancer associated with diabetes. Studies of type 1 diabetes were not included.  RRs were calculated using a random-effects model. total of 16 studies (seven case–control studies, three cohort studies and six cohort studies of diabetic patients) fulfilled the inclusion criteria. Analysis of all studies showed that diabetes was associated with an increased risk of bladder cancer, compared with no diabetes (RR = 1.24, 95% CI 1.08–1.42). There was strong evidence of heterogeneity among these studies (p < 0.0001). Stratification by study design found that diabetes was associated with an increased risk of bladder cancer in case–control studies (RR = 1.37, 95% CI 1.04–1.80, pheterogeneity = 0.005) and cohort studies (RR = 1.43, 95% CI 1.18–1.74, pheterogeneity = 0.17), but not in cohort studies of diabetic patients (RR = 1.01, 95% CI 0.91–1.12, pheterogeneity = 0.35).Conclusions/interpretationFindings from this meta-analysis suggest that individuals with diabetes may have a modestly increased risk of bladder cancer.

title: The relationship between the systemic inflammatory response and survival in patients with transitional cell carcinoma of the urinary bladder
abstract: The relationship between tumour stage, grade, elevated C-reactive protein concentration (<10/>10 mg l−1), adjuvant therapy and survival was examined in patients with biopsy proven bladder cancer (n=105). On multivariate analysis stage (HR 3.37, 95% CI 1.37–8.29, P=0.008), grade (HR 2.01, 95% CI 1.14–3.57, P=0.017) and preoperative C-reactive protein (HR 3.31, 95% CI 1.09–10.09, P=0.035) were independently associated with cancer-specific survival.

title: Preoperative plasma levels of interleukin-6 and its soluble receptor predict disease recurrence and survival of patients with bladder cancer.
abstract: Elevated levels of interleukin-6 (IL-6) are associated with metastasis and poor prognosis in various malignancies. Since the IL-6 soluble receptor (IL-6sR) potentiates the systemic effects of IL-6, each may independently impact the disease process. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder.



The study group consisted of 51 patients who underwent radical cystectomy for transitional cell carcinoma and 44 men without cancer. Preoperative plasma levels of IL-6 and IL6sR were measured by enzyme-linked immunosorbent assay and correlated with pathological features and clinical outcome.



IL-6 levels were higher in patients with bladder cancer than in healthy controls (p <0.001). In bladder cancer cases elevated levels of IL-6 and IL-6sR were associated with adverse pathological features, including muscle invasion, lymphovascular invasion and lymph node metastases (p <0.05). High levels of IL-6sR were also associated with pathological tumor grade (p = 0.036). In separate multivariate models that included clinical stage and grade IL-6 and IL-6sR levels were independent predictors of lymphovascular invasion, metastases to lymph nodes, disease recurrence and disease specific survival (p <0.05). In a preoperative Cox proportional hazards model IL-6 (p = 0.050) and IL-6sR (p = 0.035) predicted disease specific survival.



We found that plasma IL-6 levels were higher in patients with bladder cancer than in healthy controls. Levels of IL-6 and IL-6sR were associated with cancer stage and metastases, and were strong independent predictors of disease recurrence and disease specific survival.