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  • Validation of a food frequency questionnaire in the Hiroshima/Nagasaki Life Span Study.

    11 December 2018

    We evaluated the performance of a 22-item food frequency questionnaire (FFQ) administered in 1980-81 to 3,005 members of the Adult Health Study cohort, part of the Life Span Study. The questionnaire was compared with the records of a 24-hour dietary survey that was performed in 1984-85. From the dietary records, food and nutrient intakes were estimated. The association between the two measures of dietary intake was assessed using Mantel-Haenszel chi-square test and the Spearman's rank correlation coefficient. The frequency of food intake as measured by the FFQ was linearly associated with food intake as measured by the 24-hour diary, with the exception of dry fish. The highest correlations were observed for beverages, including coffee (0.51), milk (0.32) and black tea (0.26). Foods such as fruit (0.27), confectionery (0.23), rice (0.34) and bread (0.28) were also moderately correlated. These results show that, with the exception of dry fish, the FFQ is moderately correlated with the 24-hour diary and can be used to assess diet intake in this cohort.

  • Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan).

    11 December 2018

    The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. >0 to <5 g/day). A statistically significant increase in risk was observed among men consuming 45 or more grams of alcohol from liquor per day (OR = 2.23, 95% CI = 1.02-4.87, compared to 0 g/day of alcohol from liquor, P-trend = 0.12), but not among women (OR = 1.35, 95% CI = 0.63-2.87, for 30 or more g/day of alcohol from liquor, compared to none). No associations were noted for wine or beer intake. Overall, no significant increase in risk was observed, but a small effect among heavy drinkers cannot be ruled out.

  • Serum C-peptide levels and breast cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).

    11 December 2018

    It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide--a marker for pancreatic insulin secretion--in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39-1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk.

  • Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition.

    11 December 2018

    Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.

  • Intake of animal products and stroke mortality in the Hiroshima/Nagasaki Life Span Study.

    11 December 2018

    BACKGROUND: To determine whether intake of animal products was associated with a reduced risk of stroke mortality in a large-scale population-based cohort in Japan. METHODS: A self-administered questionnaire, including questions on dietary habits, was mailed to the members of the Life Span Study, a cohort of people exposed and non-exposed to atomic bomb radiation, who were alive as of 1 September 1979. Animal products included frequency intake of beef/pork, chicken, ham/sausage, milk, dairy products, eggs, fish, and broiled fish. Responses were obtained from 40 349 people (72%): 15 350 men (mean age 54 years) and 24 999 women (mean age 58 years). The subjects were followed for 16 years, and deaths were ascertained by linkage to the nationwide family registration system of Japan. The associations between diet and stroke mortality were examined using a Cox proportional hazard model. RESULTS: During the follow-up period, 1462 stroke deaths occurred. Four animal products comprising eggs, dairy products, fish, and broiled fish were independently associated with a decreased risk of stroke mortality; while beef/pork, chicken, ham/ sausage, and milk consumption were not associated with stroke death. A composite measure of eggs, dairy products, fish, and broiled fish intake was calculated, and the highest tertile was significantly inversely associated with total stroke mortality (Hazards Ratio [HR] = 0.80, 95% CI: 0.68, 0.93) compared with the lowest tertile. The protective effect of animal product intake on total stroke death was largely confined to intracerebral haemorrhage death; the RH of intracerebral haemorrhage death for the highest tertile of consumption was 0.72 (95% CI: 0.53-0.98) compared with the lowest tertile; animal products intake was not related to cerebral infarction mortality (HR = 0.84; 95% CI: 0.67-1.06). CONCLUSIONS: Intake of animal products such as eggs, dairy products, and fish may be protective against intracerebral haemorrhage, but is not related to cerebral infarction mortality.

  • Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study.

    11 December 2018

    Some dietary factors could be involved as cofactors in cervical carcinogenesis, but evidence is inconclusive. There are no data about the effect of fruits and vegetables intake (F&V) on cervical cancer from cohort studies. We examined the association between the intake of F&V and selected nutrients and the incidence of carcinoma in situ (CIS) and invasive squamous cervical cancer (ISC) in a prospective study of 299,649 women, participating in the European Prospective Investigation into Cancer and Nutrition study. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). A calibration study was used to control measurement errors in the dietary questionnaire. After a mean of 9 years of follow-up, 253 ISC and 817 CIS cases were diagnosed. In the calibrated model, we observed a statistically significant inverse association of ISC with a daily increase in intake of 100 g of total fruits (HR 0.83; 95% CI 0.72-0.98) and a statistically nonsignificant inverse association with a daily increase in intake of 100 g of total vegetables (HR 0.85: 95% CI 0.65-1.10). Statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for ISC. No association was found regarding beta-carotene, vitamin D and folic acid for ISC. None of the dietary factors examined was associated with CIS. Our study suggests a possible protective role of fruit intake and other dietary factors on ISC that need to be confirmed on a larger number of ISC cases.

  • Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition.

    11 December 2018

    Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.

  • Ethanol intake and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    11 December 2018

    To examine the association of baseline and lifetime ethanol intake with cancer of the pancreas in the European Prospective Investigation into Cancer and Nutrition (EPIC).Included in this analysis were 478,400 subjects, of whom detailed information on the intake of alcoholic beverages at baseline and over lifetime was collected between 1992 and 2000. During a median follow-up time of 8.9 years, 555 non-endocrine pancreatic cancer cases were observed. Multivariate Cox proportional hazard models were used to examine the association of ethanol intake at recruitment and average lifetime ethanol intake and pancreatic cancer adjusting for smoking, height, weight, and history of diabetes.Overall, neither ethanol intake at recruitment (relative risk (RR) = 0.94, 95% confidence interval (CI) 0.69-1.27 comparing 30+ g/d vs. 0.1-4.9 g/d) nor average lifetime ethanol intake (RR = 0.95, 95% CI 0.65-1.39) was associated with pancreatic cancer risk. High lifetime ethanol intake from spirits/liquor at recruitment tended to be associated with a higher risk (RR = 1.40, 95% CI 0.93-2.10 comparing 10+ g/d vs. 0.1-4.9 g/d), but no associations were observed for wine and beer consumption.These results suggest no association of alcohol consumption with the risk of pancreatic cancer.

  • Lifetime and baseline alcohol intake and risk of cancer of the upper aero-digestive tract in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

    11 December 2018

    Recent alcohol consumption is an established risk factor for squamous cell carcinoma (SCC) of the upper aero-digestive tract. In contrast, the role of lifetime exposure to alcohol with regard to risk of SCC is not well established. Historical data on alcohol use are available in 271,253 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 2,330,381 person years, 392 incident SCC cases (279 men and 113 women) were identified. Cox regression was applied to model sex-specific associations between lifetime alcohol intake and SCC risk adjusting for potential confounders including smoking. Compared to men who drank 0.1-6.0 g/day alcohol at lifetime, the relative risks (RR) for developing SCC were significantly increased for men who drank 30.1-60.0 g/day (RR 1.65, 95% confidence interval:1.00-2.71), 60.1-96.0 g/day (RR 2.20, 95%CI 1.23-3.95), and >96.0 g/day, (RR 4.63, 95% CI 2.52-8.48), and for former drinkers (RR 4.14, 95%CI 2.38-7.19). These risk estimates did not considerably change when baseline alcohol intake was analyzed. Compared to women who drank 0.1-6.0 g/day alcohol intake at lifetime, the RR were significantly increased for women who drank >30 g/d (RR 6.05, 95%CI 2.98-12.3). Applying similar categories, the relative risk for baseline alcohol intake was 3.26 (95%CI 1.82-5.87). We observed a stronger association between alcohol intake at lifetime and risk of SCC in women compared to men (p for interaction = 0.045). The strong dose-response relation for lifetime alcohol use underscores that alcohol is an important risk factor of SCC of the upper aero-digestive tract throughout life.

  • Physical activity and risk of endometrial cancer: the European prospective investigation into cancer and nutrition.

    11 December 2018

    The etiologic role of physical activity in endometrial cancer risk remains unclear given the few epidemiologic studies that have been conducted. To investigate this relation more fully, an analysis was undertaken in the European prospective investigation into cancer and nutrition (EPIC). During an average 6.6 years of follow-up, 689 incident endometrial cancer cases were identified from an analytic cohort within EPIC of 253,023 women. Cox proportional hazards models were used to estimate the associations between type of activity (total, occupational, household, recreational) and endometrial cancer risk. For total activity, women in the highest compared with the lowest quartile of activity had a risk of 0.88 (95% confidence interval (95% CI=0.61-1.27). No clear associations between each type of activity and endometrial cancer risk were found for the total study population combined. Associations were more evident in the stratified results, with premenopausal women who were active versus inactive experiencing a risk of 0.66 (95% CI=0.38-1.14) overall. Among premenopausal women, for household and recreational activities the risk estimates in the highest as compared with the lowest quartiles were, respectively, 0.48 (95% CI=0.23-0.99) and 0.78 (95% CI=0.44-1.39). No effect modification by body mass index, hormone replacement therapy, oral contraceptive use or energy intake was found. This study provides no evidence of a protective effect of increased physical activity in endometrial cancer risk in all women but some support for a benefit among premenopausal women. The relative risk reductions are most apparent for household activities.