Periodontal disease and risk of all cancers among male never smokers: an updated analysis of the Health Professionals Follow-up Study.

BACKGROUND: Periodontal disease has a direct impact on the immune response and has been linked to several chronic diseases, including atherosclerosis and stroke. Few studies have examined the association between periodontal disease and cancer. PATIENTS AND METHODS: A total of 19 933 men reported being never smokers (of cigarette, pipes or cigars) in the Health Professionals' Follow-up Study. Periodontal disease status and teeth number were self-reported at baseline and during follow-up. All cancers were ascertained during 26 years of follow-up. Cox's proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) adjusting for risk factors. RESULTS: A 13% increase in total cancer was observed among men reporting periodontitis at baseline, and a 45% increase in risk was observed among men with advanced periodontitis (periodontitis with <17 remaining teeth). Periodontitis was not associated with prostate cancer, colorectal cancer or melanoma, the three most common cancers in this cohort of never smokers, but a 33% increase in risk was observed for smoking-related cancers (lung, bladder, oropharnygeal, esophageal, kidney, stomach and liver cancers; HR = 1.33, 95% CI 1.07-1.65). Men with advanced periodontitis had an HR of 2.57 (95% CI 1.56-4.21; P = 0.0002) for smoking-related cancers, compared with men who did not have periodontitis and had 17 teeth or more. Advanced periodontitis was associated with elevated risks of esophageal and head and neck cancers (HR = 6.29, 95% CI 2.13-18.6; based on five cases with advanced periodontitis) and bladder cancer (HR = 5.06, 95% CI 2.32-11.0; based on nine cases with advanced periodontitis). CONCLUSIONS: Advanced periodontitis was associated with a 2.5-fold increase in smoking-related cancers among never smokers. Periodontitis may impact cancer risk through system immune dysregulation. Further studies need to examine the immune impact of advanced periodontitis on cancer, especially for cancers known to be caused by smoking.

Occupational asphalt is not associated with head and neck cancer.

BACKGROUND: Epidemiologic studies that evaluate the relationship between occupational asphalt exposure and head and neck cancer have had a limited ability to control for known risk factors such as smoking, alcohol and human papillomavirus (HPV). AIMS: To better elucidate this relationship by including known risk factors in a large case-control study of head and neck squamous cell carcinoma (HNSCC) from the greater Boston area. METHODS: We analysed the relationship between occupational asphalt exposure and HNSCC among men in the Greater Boston area of Massachusetts. Analyses were conducted using unconditional multivariable logistic regression, performed with adjustments for age, race, education, smoking, alcohol consumption and HPV serology. RESULTS: There were 753 cases and 913 controls. No associations between HNSCC and occupational asphalt exposure (neither among ever-exposed nor by occupational duration) were observed for exposures in any occupation or those restricted to the construction industry. We also observed no associations in subgroup analyses of never-smokers and ever-smokers. Adjusting for known risk factors further reduced the estimated effect of asphalt exposure on HNSCC risk. CONCLUSIONS: We found no evidence for an association between occupational asphalt exposure and HNSCC. The null findings from this well-controlled analysis could suggest that the risk estimates stemming from occupational cohort studies may be overestimated due to uncontrolled confounding and enhance the literature available for weighing cancer risk from occupational exposure to bitumen.

Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort.

BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables. RESULTS: Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154). CONCLUSION: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.

Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

AIMS/HYPOTHESIS: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. METHODS: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. RESULTS: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥ 6.5%, 48 mmol/mol] vs lowest [≤ 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. CONCLUSIONS/INTERPRETATION: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.

Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies.

BACKGROUND: Studies evaluating vitamin D status in relation to pancreatic cancer risk have yielded inconsistent results. METHODS: We prospectively followed 118 597 participants in the Nurses' Health Study and Health Professionals Follow-up Study from 1986 to 2006. We calculated a 25-hydroxyvitamin D (25(OH)D) score from known predictors of vitamin D status for each individual and then examined the predicted 25(OH)D levels in relation to pancreatic cancer risk. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models adjusted for age, sex, race, height, smoking, and diabetes. We then further adjusted for body mass index (BMI) and physical activity in a sensitivity analysis. RESULTS: During 20 years of follow-up, we identified 575 incident pancreatic cancer cases. Higher 25(OH)D score was associated with a significant reduction in pancreatic cancer risk; compared with the lowest quintile, participants in the highest quintile of 25(OH)D score had an adjusted RR of 0.65 (95% CI=0.50-0.86; P(trend)=0.001). Results were similar when we further adjusted for BMI and physical activity. CONCLUSIONS: Higher 25(OH)D score was associated with a lower risk of pancreatic cancer in these two prospective cohort studies.

Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts.

Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and blockade of the IGF-I receptor has antitumour activity. The association of plasma IGF-I and IGF binding protein-3 (IGFBP-3) with pancreatic cancer risk has been investigated in two small studies, with conflicting results. We conducted a nested case-control study within four large, prospective cohorts to investigate whether prediagnostic plasma levels of IGF-I, IGF-II, and IGFBP-3 were associated with pancreatic cancer risk. Plasma levels in 212 cases and 635 matched controls were compared by conditional logistic regression, with adjustment for other known pancreatic cancer risk factors. No association was observed between plasma levels of IGF-I, IGF-II, or IGFBP-3 and incident diagnosis of pancreatic cancer. Relative risks for the highest vs the lowest quartile of IGF-I, IGF-II, and IGFBP-3 were 0.94 (95% confidence interval (CI), 0.60-1.48), 0.96 (95% CI, 0.61-1.52), and 1.21 (95% CI, 0.75-1.92), respectively. The relative risk for the molar ratio of IGF-I and IGFBP-3, a surrogate measure for free IGF-I, was 0.84 (95% CI, 0.54-1.31). Additionally, no association was noted in stratified analyses or when requiring longer follow-up. In four prospective cohorts, we found no association between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I, IGF-II, or IGFBP-3.

Gonorrhoea and male bladder cancer in a prospective study.

In a prospective cohort study, a close to two-fold elevated risk of bladder cancer was found among men reporting a history of gonorrhoea (relative risk=1.92, 95% CI=1.10-3.33). Our finding warrants further examination of the role of gonorrhoea in bladder carcinogenesis.

Event-related potential measures of the disruptive effects of trains of auditory stimuli during waking and sleeping states.

Acoustic backup alarms have been reported to particularly disrupt sleep. The present study simulated backup alarms by presenting trains of five consecutive 500 ms duration audible tones, with the time between the onset of each tone being 1 s and the time between trains (offset to onset) between 15 and 20 s. In different conditions, the tones were set at either 80 or 60 dB sound pressure level (SPL). Twelve young adults spent two consecutive nights in the laboratory. Stimuli were presented only on the second night. Measures of traditional sleep architecture (sleep stages) were not affected by the acoustic trains. Event-related potentials were also measured following presentation of the stimuli. In the waking state, the initial 80 dB stimulus elicited a large amplitude N1, peaking at about 100 ms, followed by a positive peak, P3, peaking at about 325 ms. N1 was attenuated following presentation of the 60 dB stimulus. The amplitude of N1 was much reduced following presentation of the subsequent second to fifth stimuli in the train. During non-rapid eye movement (NREM) sleep, the initial 80 dB stimulus elicited a large and later negativity (N350) that was reduced in amplitude for the 60 dB stimulus. A K-Complex (a composite N350 and a much larger N550) was elicited following 35% of the initial 80 dB tones and 12% of the initial 60 dB tones. The amplitude of N550 did not, however, significantly vary as a function of stimulus SPL. During REM sleep, N1 continued to be elicited by the initial louder stimulus, but the later positive wave was not apparent. A late negativity peaking at about 350 ms was, however, apparent. When queried the next morning, subjects rarely indicated that the stimulus presentations disturbed their sleep. This might be because of the absence of the late positivity. The presence of the long latency negativities (N350 and N550) might serve to protect sleep from obtrusive sound during sleep.

Toenail selenium concentrations and bladder cancer risk in women and men.

Prediagnostic selenium concentrations measured in archived toenails were inversely associated with bladder cancer risk in women (P for trend = 0.02), but not in men, in a nested case-control study of 338 cases and 341 matched controls. These findings may be due to chance and more studies are needed to determine whether associations between selenium and bladder cancer risk differ by sex.

Noise annoyance in Canada.

The present paper provides the results from two nation-wide telephone surveys conducted in Canada on a representative sample of 5,232 individuals, 15 years of age and older. The goals of this study were to gauge Canadians' annoyance towards environmental noise, identify the source of noise that is viewed as most annoying and quantify annoyance toward this principal noise source according to internationally accepted specifications. The first survey revealed that nearly 8% of Canadians in this age group were either very or extremely bothered, disturbed or annoyed by noise in general and traffic noise was identified as being the most annoying source. A follow-up survey was conducted to further assess Canadians' annoyance towards traffic noise using both a five-item verbal scale and a ten-point numerical scale. It was shown that 6.7% of respondents indicated they were either very or extremely annoyed by traffic noise on the verbal scale. On the numerical scale, where 10 was equivalent to "extremely annoyed" and 0 was equivalent to "not at all annoyed", 5.0% and 9.1% of respondents rated traffic noise as 8 and above and 7 and above, respectively. The national margin of error for these findings is plus or minus 1.9 percentage points, 19 times out of 20. The results are consistent with an approximate value of 7% for the percentage of Canadians, in the age group studied, highly annoyed by road traffic noise (i.e. about 1.8 million people). We found that age, education level and community size had a statistically significant association with noise annoyance ratings in general and annoyance specifically attributed to traffic noise. The use of the International Organization for Standardization/Technical Specification (ISO/TS)-15666 questions for assessing noise annoyance makes it possible to compare our results to other national surveys that have used the same questions.

Epidemiology of pancreatic cancer.

Worldwide, over 200000 people die annually of pancreatic cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. In the United States, pancreatic cancer is the 4(th) leading cause of cancer death, and in Europe it is the 6th. Because of high fatality rates, pancreatic cancer incidence rates are almost equal to mortality rates. Pancreatic cancer is diagnosed late in the natural history of the disease, given the few early indicators of illness, and the lack of screening tests for this disease. Treatment has not improved substantially over the past few decades and has little effect on prolonging survival time. Therefore, prevention could play an important role in reducing pancreatic cancer mortality. International variations in rates and time trends suggest that environmental factors are likely to play a role in the etiology of pancreatic cancer. Variations in rates are substantial and occur even within industrialized nations. While rates have been stabilizing over the past 2 decades in many countries where they are already high, they continue to increase in countries where rates were relatively low 4 decades ago, such as Japan. In the US, the highest rates of pancreatic cancer incidence and mortality are observed among blacks, who have some of the highest rates in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. A number of studies observed a reduction in pancreatic cancer risk within a decade after smoking cessation, when compared to current smokers. With tobacco smoking as an exception, risk factors for pancreatic cancer are not well-established. Over the past 2 decades, epidemiological studies on pancreatic cancer have been plagued with methodological issues associated with studying a highly fatal disease, and inconsistent findings have hindered our understanding of the etiology of pancreatic cancer. Although familial pancreatic cancer is well-documented, the genes responsible for this condition have not been identified and are unlikely to explain more than 5-10% of all pancreatic cancer cases. Chronic pancreatitis and diabetes mellitus are medical conditions that have been consistently related to pancreatic cancer. Data from numerous studies suggest that these conditions are likely to be causally related to pancreatic cancer, rather than being consequences of the cancer. Recent cohort studies, which are less prone to biases than case-control studies, suggest that obesity increases the risk of pancreatic cancer. Other studies support the hypothesis that glucose intolerance and hyperinsulinemia are important in the development of pancreatic cancer. Other potential risk factors include physical inactivity, aspirin use, occupational exposure to certain pesticides, and dietary factors such as carbohydrate or sugar intake.

Does amygdaloid corticotropin-releasing hormone (CRH) mediate anxiety-like behaviors? Dissociation of anxiogenic effects and CRH release.

The brain corticotropin-releasing hormone (CRH) circuits are activated by stressful stimuli, contributing to behavioral and emotional responses. The present study assessed anxiety-like responses and in vivo neurochemical alterations at the central nucleus of the amygdala (CeA) evoked by exposure to an unfamiliar (anxiogenic) environment. Also, the impact of anxiolytic treatments and those that affect CRH were assessed in this paradigm. Novel environment (new cage) markedly suppressed ingestion of a palatable snack. This effect was dose-dependently antagonized by diazepam and was utilized as an index of anxiety in the rodent. Although exposure to a novel environment also stimulated the in vivo release of CRH and glutamate at the CeA, various CRH antagonists (e.g. alphah-CRH, Calpha-MeCRH, CP-154,526, antisauvagine-30, preproTRH178-199) did not attenuate the stressor-elicited behavioral suppression, although Calpha-MeCRH was found to attenuate the freezing response elicited by contextual stimuli that were associated with previously administered footshock. Moreover, central infusion of CRH failed to suppress snack consumption in the home cage. Although diazepam had potent anxiolytic effects in this paradigm, this treatment did not prevent the stressor-associated release of CRH and glutamate at the CeA. Thus, while neural circuits involving CRH and/or glutamatergic receptors at the CeA may be activated by an unfamiliar environment, the data challenge the view that activation of these receptors is necessary for the expression of anxiety-like behavioral responses. Rather than provoking anxiety, these systems might serve to draw attention to events or cues of biological significance, including those posing a threat to survival.

Aspirin use and lung cancer in men.

We examined prospectively the relation between regular aspirin use and lung cancer risk in the Health Professionals Follow-Up Study. Of 49,383 US men aged 40-75 years who completed biennial self-administered questionnaires that assessed aspirin use beginning in 1986, 328 developed lung cancer during 601,453 person-years of follow-up through 31 December 2000. No information on aspirin dose was available. Controlling for current age, smoking status, and age at starting to smoke regularly, the relative risk (RR) of total lung cancer for regular users of aspirin (twice or more per week) at baseline compared to nonusers was 1.13 (95% confidence interval (CI) =0.89-1.43). Results were similar for non-small-cell lung cancer (RR=1.16; 95% CI=0.88-1.54). No apparent dose-dependent association was observed for the frequency of aspirin use and lung cancer risk (P for trend=0.64), and results remained null when consistent use of aspirin over time was examined. These findings do not suggest that regular aspirin use is associated with a reduced lung cancer risk.

Cholecystectomy and the risk for developing colorectal cancer and distal colorectal adenomas.

Earlier work describes a modest association between cholecystectomy and the risk of colorectal cancer. We conducted a prospective study of 85 184 women, 36-61 years old, who had no history of cancer to evaluate whether known risk factors for colorectal cancer, including dietary history, that have not been controlled for in previous analyses can help explain the observed association. During 16 years of follow-up, 877 cases of colorectal cancer were documented and 1452 women who underwent endoscopy during the follow-up time were diagnosed with distal adenomas. After adjustment for age and other known or suspected risk factors, we found a significant, positive association between cholecystectomy and the risk of colorectal cancer (multivariate relative risk RR 1.21, 95% CI 1.01-1.46). The risk was highest for cancers of the proximal colon (RR 1.34, 95% CI 0.97-1.88) and the rectum (RR 1.58, 95% CI 1.05-2.36). However, we did not observe a significant association between cholecystectomy and distal colorectal adenomas. In this large prospective cohort study, a history of cholecystectomy appears to increase modestly the risk of colorectal cancer, even after adjustment for other colorectal cancer risk factors.

Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study.

We examined the relation between dietary fruit and vegetables, carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospective cohort study. Over a median of 11 years, we followed 27 111 male smokers aged 50-69 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. During this period, 344 men developed bladder cancer. All of these men had completed a 276-food item dietary questionnaire at baseline. Cox proportional hazards models were used to estimate the relative risks and 95% confidence intervals and to simultaneously adjust for age, smoking history, energy intake and intervention group. Consumption of fruits and vegetables was not associated with the risk of bladder cancer (relative risk=1.28; 95% confidence intervals CI: 0.89-1.84, for highest vs lowest quintile). Similarly, no associations were observed for groups of fruits or vegetables (berries and cruciferous vegetables), or for specific fruits and vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not related to the risk of bladder cancer. These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk. However, these results may not be generalisable to non-smokers.

Gallstones, cholecystectomy, and the risk for developing pancreatic cancer.

We examined the relation between gallstones, cholecystectomy, and the development of pancreatic cancer in the Nurses' Health Study and the Health Professionals Follow-up Study. Among 104,856 women and 48,928 men without cancer at baseline, we documented 349 cases of pancreatic cancer during up to 16 years of follow-up. Participants were classified according to a history of gallstones or cholecystectomy. The age-adjusted relative risk of pancreatic cancer following cholecystectomy or diagnosis of gallstones was 1.31 (95% CI, 0.93-1.83). However, adjustment for other pancreatic cancer risk factors attenuated the association (RR=1.11, 95% CI, 0.78-1.56); this risk did not increase with increasing time following cholecystectomy or gallstones. Gallstones or cholecystectomy do not appear to be significant risk factors for pancreatic cancer.

Design and serendipity in establishing a large cohort with wide dietary intake distributions : the National Institutes of Health-American Association of Retired Persons Diet and Health Study.

In 1995-1996, the authors mailed a food frequency questionnaire to 3.5 million American Association of Retired Persons members who were aged 50-69 years and who resided in one of six states or two metropolitan areas with high-quality cancer registries. In establishing a cohort of 567,169 persons (340,148 men and 227,021 women), the authors were fortunate in that a less-than-anticipated baseline response rate (threatening inadequate numbers of respondents in the intake extremes) was offset by both a shifting and a widening of the intake distributions among those who provided satisfactory data. Reported median intakes for the first and fifth intake quintiles, respectively, were 20.4 and 40.1 (men) and 20.1 and 40.0 (women) percent calories from fat, 10.3 and 32.0 (men) and 8.7 and 28.7 (women) g per day of dietary fiber, 3.1 and 11.6 (men) and 2.8 and 11.3 (women) servings per day of fruits and vegetables, and 20.7 and 156.8 (men) and 10.5 and 97.0 (women) g per day of red meat. After 5 years of follow-up, the cohort is expected to yield nearly 4,000 breast cancers, more than 10,000 prostate cancers, more than 4,000 colorectal cancers, and more than 900 pancreatic cancers. The large size and wide intake range of the cohort will provide ample power for examining a number of important diet and cancer hypotheses.

Risk of bladder cancer by geographic region in a U.S. cohort of male health professionals.

Large regional variations in bladder cancer rates have been observed for numerous decades in the United States and persist to date. We examined the incidence rates of bladder cancer by geographic region among U.S. male health professionals to determine whether diet or other lifestyle factors can account for variations observed. During 12 years of follow-up, 328 cases of bladder cancer were diagnosed in the Health Professionals Follow-up Study cohort. We inquired about diet, lifetime history of smoking, race, marital status, and other nondietary factors using mailed questionnaires. An elevated risk of bladder cancer was observed in the Northeast compared with the West [relative risk (RR) = 1.71, 95% confidence interval (CI) = 1.23-2.39], which was slightly attenuated after controlling for smoking (RR = 1.65, 95% CI = 1.18-2.30). Smoking patterns, diet, and other lifestyle factors could not account for all of the elevated bladder cancer risk in the Northeast. Bladder cancer risk was highest among men who had a long residency in the Northeast compared with a long residency in the West (RR = 1.77, 95% CI = 1.15-2.71, adjusted for smoking). Diet and other known characteristics do not appear to be responsible for the regional variations in bladder cancer rates in the United States.

Physical activity, obesity, height, and the risk of pancreatic cancer.

CONTEXT: Diabetes mellitus and elevated postload plasma glucose levels have been associated with an increased risk of pancreatic cancer in previous studies. By virtue of their influence on insulin resistance, obesity and physical inactivity may increase risk of pancreatic cancer. OBJECTIVE: To examine obesity, height, and physical activity in relation to pancreatic cancer risk. DESIGN AND SETTING: Two US cohort studies conducted by mailed questionnaire, the Health Professionals Follow-up Study (initiated in 1986) and the Nurses' Health Study (initiated in 1976), with 10 to 20 years of follow-up. PARTICIPANTS: A total of 46 648 men aged 40 to 75 years and 117 041 women aged 30 to 55 years who were free of prior cancer at baseline and had complete data on height and weight. MAIN OUTCOME MEASURES: Relative risk of pancreatic cancer, analyzed by self-reported body mass index (BMI), height, and level of physical activity. RESULTS: During follow-up, we documented 350 incident pancreatic cancer cases. Individuals with a BMI of at least 30 kg/m(2) had an elevated risk of pancreatic cancer compared with those with a BMI of less than 23 kg/m(2) (multivariable relative risk [RR], 1.72; 95% confidence interval [CI], 1.19-2.48). Height was associated with an increased pancreatic cancer risk (multivariable RR, 1.81; 95% CI, 1.31-2.52 for the highest vs lowest categories). An inverse relation was observed for moderate activity (multivariable RR, 0.45; 95% CI, 0.29-0.70 for the highest vs lowest categories; P for trend <.001). Total physical activity was not associated with risk among individuals with a BMI of less than 25 kg/m(2) but was inversely associated with risk among individuals with a BMI of at least 25 kg/m(2) (pooled multivariable RR, 0.59; 95% CI, 0.37-0.94 for the top vs bottom tertiles of total physical activity; P for trend =.04). CONCLUSION: In 2 prospective cohort studies, obesity significantly increased the risk of pancreatic cancer. Physical activity appears to decrease the risk of pancreatic cancer, especially among those who are overweight.