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.

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.

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.

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.

Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort.

BACKGROUND: Previous epidemiologic studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results, especially with regard to the types of fruits and vegetables consumed. We examined total fruit and vegetable intake, as well as intakes of subtypes of fruits and vegetables, in relation to bladder cancer risk in a large male prospective cohort study. METHODS: Two hundred fifty-two cases of incident bladder cancer were diagnosed from 1986 through January 31, 1996, among 47,909 men enrolled in the Health Professionals Follow-up Study. Each participant in this cohort completed a 131-item food-frequency questionnaire in 1986 and subsequently in 1990 and 1994. We used logistic regression analyses to examine fruit and vegetable intake in relation to bladder cancer risk, after adjusting for age, history of cigarette smoking, current smoking status, geographic region, total fluid intake, and caloric intake. RESULTS: We observed a weak, inverse association that was not statistically significant between total fruit and vegetable intake and bladder cancer risk. Intake of cruciferous vegetables was inversely associated with risk (relative risk = 0.49; 95% confidence interval = 0.32-0.75, for the highest category of cruciferous vegetable intake compared with the lowest), but intakes of yellow or green leafy vegetables or carotenoid-rich vegetables were not associated with risk. Individual cruciferous vegetables, except for coleslaw, were all inversely related to bladder cancer risk, but only the associations for broccoli and cabbage were statistically significant. CONCLUSIONS: Data from this study indicate that high cruciferous vegetable consumption may reduce bladder cancer risk, but other vegetables and fruits may not confer appreciable benefits against this cancer.

Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women.

BACKGROUND: In animal studies, prolactin has been found to be important for mammary epithelial development and its administration has been shown consistently to increase the rate of mammary tumor formation. Previous epidemiologic studies of prolactin and breast cancer risk in postmenopausal women have been limited in size, and the results have been inconsistent. We conducted a nested case-control study within the prospective Nurses' Health Study cohort to better determine the relationship between plasma prolactin levels and postmenopausal breast cancer risk. METHODS: Blood samples were collected from cohort members during the period from 1989 through 1990. Prolactin levels were measured by use of a microparticle enzyme immunoassay. Included in this analysis were 306 postmenopausal women who were diagnosed with breast cancer after blood donation but before June 1994. One or two postmenopausal control subjects were matched per case subject on the basis of age, postmenopausal hormone use, and time of day and month of blood collection; the study included a total of 448 control subjects. RESULTS: In conditional logistic regression analyses, a significant positive association was observed between plasma level of prolactin and postmenopausal breast cancer risk (highest versus lowest quartile, multivariate relative risk = 2.03; 95% confidence interval = 1.24-3.31; two-sided P for trend = .01). The relationship was independent of plasma sex steroid hormone levels and was similar after excluding case subjects diagnosed in the first 2 years after blood collection. CONCLUSIONS: These prospective data suggest that higher plasma prolactin levels are associated with an increased risk of breast cancer in postmenopausal women.

Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women.

BACKGROUND: Diets high in fruits and vegetables have been shown to be associated with a lower risk of lung cancer. beta-Carotene was hypothesized to be largely responsible for the apparent protective effect, but this hypothesis was not supported by clinical trials. METHODS: We examined the association between lung cancer risk and fruit and vegetable consumption in 77 283 women in the Nurses' Health Study and 47 778 men in the Health Professionals' Follow-up Study. Diet was assessed with the use of a food-frequency questionnaire that included 15 fruits and 23 vegetables. We used logistic regression models to estimate relative risks (RRs) of lung cancer within each cohort. All statistical tests were two-sided. RESULTS: We documented 519 lung cancer cases among the women and 274 among the men. Total fruit and vegetable consumption was associated with a modestly lower risk of lung cancer among the women but not among the men. The RR for the highest versus lowest quintile of intake was 0.79 (95% confidence interval [CI] = 0.59-1.06) among the women and 1.12 (95% CI = 0.74-1.69) among the men after adjustment for smoking status, quantity of cigarettes smoked per day, time since quitting smoking, and age at initiation of smoking. However, total fruit and vegetable consumption was associated with a lower risk of lung cancer among never smokers in the combined cohorts, although the reduction was not statistically significant (RR = 0.63; 95% CI = 0.35-1.12 in the highest tertile). CONCLUSION: Higher fruit and vegetable intakes were associated with lower risks of lung cancer in women but not in men. It is possible that the inverse association among the women remained confounded by unmeasured smoking characteristics, although fruits and vegetables were protective in both men and women who never smoked.

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.

Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts.

BACKGROUND: Carotenoids may reduce lung carcinogenesis because of their antioxidant properties; however, few studies have examined the relation between intakes of individual carotenoids and lung cancer risk. OBJECTIVE: The aim of this study was to examine the relation between lung cancer risk and intakes of alpha-carotene, beta-carotene, lutein, lycopene, and beta-cryptoxanthin in 2 large cohorts. DESIGN: During a 10-y follow-up period, 275 new cases of lung cancer were diagnosed in 46924 men; during a 12-y follow-up period, 519 new cases were diagnosed in 77283 women. Carotenoid intakes were derived from the reported consumption of fruit and vegetables on food-frequency questionnaires administered at baseline and during follow-up. The data were analyzed separately for each cohort and the results were pooled to compute overall relative risks (RRs). RESULTS: In the pooled analyses, alpha-carotene and lycopene intakes were significantly associated with a lower risk of lung cancer; the association with beta-carotene, lutein, and beta-cryptoxanthin intakes were inverse but not significant. Lung cancer risk was significantly lower in subjects who consumed a diet high in a variety of carotenoids (RR: 0.68; 95% CI: 0.49, 0.94 for highest compared with lowest total carotenoid score category). Inverse associations were strongest after a 4-8-y lag between dietary assessment and date of diagnosis. In subjects who never smoked, a 63% lower incidence of lung cancer was observed for the top compared with the bottom quintile of alpha-carotene intake (RR: 0.37; 95% CI: 0.18, 0.77). CONCLUSION: Data from 2 cohort studies suggest that several carotenoids may reduce the risk of lung cancer.

Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts.

Although most prospective cohort studies do not support an association between coffee consumption and pancreatic cancer, the findings for alcohol are inconsistent. Recently, a large prospective cohort study of women reported statistically significant elevations in risk of pancreatic cancer for both coffee and alcoholic beverage consumption. We obtained data on coffee, alcohol, and other dietary factors using semiquantitative food frequency questionnaires administered at baseline (1986 in the Health Professionals Follow-Up Study and 1980 in the Nurses' Health Study) and in subsequent follow-up questionnaires. Data on other risk factors for pancreatic cancer, including cigarette smoking, were also available. Individuals with a history of cancer at study initiation were excluded from all of the analyses. During the 1,907,222 person-years of follow-up, 288 incident cases of pancreatic cancer were diagnosed. The data were analyzed separately for each cohort, and results were pooled to compute overall relative risks (RR). Neither coffee nor alcohol intakes were associated with an increased risk of pancreatic cancer in either cohort or after pooling the results (pooled RR, 0.62; 95% confidence interval, 0.27-1.43, for >3 cups of coffee/day versus none; and pooled RR, 1.00; 95% confidence interval, 0.57-1.76, for > or = 30 grams of alcohol/day versus none). The associations did not change with analyses examining different latency periods for coffee and alcohol. Similarly, no statistically significant associations were observed for intakes of tea, decaffeinated coffee, total caffeine, or alcoholic beverages. Data from these two large cohorts do not support any overall association between coffee intake or alcohol intake and risk of pancreatic cancer.

Associations of plasma carotenoid concentrations and dietary intake of specific carotenoids in samples of two prospective cohort studies using a new carotenoid database.

Diet-plasma carotenoid associations were examined in samples of women and men from each cohort in the Nurses' Health Study and the Health Professionals Follow-Up Study. In each sample, participants completed two self-administered food frequency questionnaires with at least a 1-year interval and provided a blood specimen preceding the second food frequency questionnaire. Carotenoid intakes were estimated from values for the five major carotenoids found in human plasma, specifically, alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene, using the United States Department of Agriculture-National Cancer Institute Carotenoid Database, as well as updated values for tomato products. Pearson correlation coefficients were calculated to compare diet-plasma correlations over time by sex after adjustment for recognized covariates. Among nonsmoking women (n = 162), the adjusted diet-plasma carotenoid associations were 0.48 for alpha-carotene, 0.27 for beta-carotene and lutein, 0.32 for beta-cryptoxanthin, and 0.21 for lycopene. Among nonsmoking men (n = 110), diet-plasma correlations were 0.47 for alpha-carotene and lycopene, 0.35 for beta-carotene, 0.43 for beta-cryptoxanthin, and 0.40 for lutein. Correlations between total fruit or vegetable intake and each plasma carotenoid level were not as high as any of the calculated carotenoid intake using the new database values. The correlations observed in this study indicate that the new carotenoid database provides valuable information on specific carotenoid intake and may be useful in epidemiological studies that attempt to account for associations between fruit or vegetable intake and disease.

Reproducibility of plasma and urinary sex hormone levels in premenopausal women over a one-year period.

Although endogenous sex steroid hormones in premenopausal women may be associated with the risk of breast cancer and other illnesses, direct evidence to support this hypothesis is limited in large part by methodological issues in the conduct of relevant studies. One major unresolved issue is whether a single blood sample (such as is available in most epidemiological studies), collected in a specific phase of the menstrual cycle, reflects long-term levels in that phase. To address this issue, two sets of blood and urine samples were obtained from 87 premenopausal women over a 1-year period in both the follicular and luteal phases. Plasma estradiol, estrone, and estrone sulfate were measured in the blood samples obtained in both phases, whereas progesterone and urinary 2- and 16a-hydroxyestrone were measured in luteal-phase samples only. For all of the women combined, intraclass correlation coefficients (ICCs) ranged, with one exception, from 0.52 to 0.71 for the plasma estrogens and the urinary estrogen metabolites. The sole exception was for estradiol in the luteal phase (ICC = 0.19); inclusion of only women who were ovulatory in both cycles and who collected each sample 4-10 days before their next period resulted in a substantially higher ICC for estradiol in the luteal phase (ICC = 0.62; 95% confidence interval, 0.43-0.78). These data indicate that, for several plasma and urinary sex hormones, a single follicular- or luteal-phase measurement in premenopausal women is reasonably representative of hormone levels in that phase for at least a 1-year period.

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.

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.

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.

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.

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.

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.