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BackgroundCancer ranks as the second leading cause of death among children ages 1 to 14 years in the United States. Previous research finds that strong cohort selection in utero against males precedes a reduction in live-born males considered frail. We examine whether such cohort selection in utero may similarly affect the frequency of childhood cancers among male live births.MethodsWe examined 1,368 childhood cancers among males born in Sweden over 144 months, from January 1990 to December 2001, and followed to age 15 in the Swedish Cancer Registry. We retrieved the count of male twins by birth month from the Swedish Birth Registry. We applied autoregressive, integrated, moving average time-series methods to identify and control for temporal patterns in monthly childhood cancers and to evaluate robustness of results.ResultsFewer childhood cancers occur among monthly male birth cohorts with elevated selection in utero (i.e., a low count of live-born male twins). This association appears in the concurrent month (coef = 0.04; 95% CI, 0.001-0.079) as well as in the following month in which most births from the twin's conception cohort are "scheduled" to be born (coef = 0.055; 95% CI, 0.017-0.094).ConclusionsElevated cohort selection in utero may reduce the number of frail male gestations that would otherwise have survived to birth and received a cancer diagnosis during childhood.ImpactThis novel result warrants further investigation of prenatal exposures, including those at the population level, that may induce cohort selection in utero for some cancer types but not others.

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to

BackgroundThe incidence pattern of gastric cancer by histological types across major race/ethnic groups is unknown.MethodsAge-standardized rates from 1992-2016 by race/ethnicity were calculated using data from Surveillance, Epidemiology, and End Results Program (SEER). Annual percent changes (APCs) in rates and corresponding 95% confidence intervals (CIs) were calculated and pairwise comparison of rates between race/ethnic groups was performed using the Joinpoint Regression Program. Calendar periods of incidence rates of gastric cardia and non-cardia cancer by histological types across race/ethnicity groups were shown by figures.ResultsThe White population has the highest incidence of gastric cardia adenocarcinoma and the incidence is keeping constant from 1992 through 2016 except the decreasing in the Asian population (AAPC = -1.4, 95%CI (-2.1, -0.8)). Although the incidence of non-cardia adenocarcinoma is decreasing in each group, the descending trend in the Asian population is the quickest (AAPC = -3.8, 95%CI (-4.0, -3.5)). Gastric carcinoids were observed to have statistically significant increasing trends in all race/ethnicity groups, especially in Hispanic women from 0.4 per 100,000 to 1.6 per 100,000 persons. The incidence of gastrointestinal stromal tumors (GISTs) is rising, with Non-Hispanic blacks having the highest incidence.ConclusionThis study demonstrated disparities in the incidence of gastric cancer by histological types among different race/ethnic groups. Further investigations are warranted to understand the changing incidence patterns by race/ethnicity.

BACKGROUND:White cell count (WCC) is a clinical marker of inflammation. Data are limited regarding the association of total and differential WCC with risk of mortality, and its role related with smoking and body mass index (BMI). METHODS:A total of 14 433 participants (4150 men; 10 283 women; average age 47.3±11.8 years) from the Dutch European Prospective Investigation into Cancer and Nutrition-Netherlands cohort were included. The associations between prediagnostic total WCC and its subtypes and risk of all-cause, cancer and cardiovascular disease (CVD) mortality were assessed. The role of WCC related with smoking and BMI on mortality was further explored. Multivariate Cox regression models were performed to estimate the HR and 95% CI. RESULTS:After an average follow-up of 15.8 years, a total of 936 death cases were identified (466 cancer; 179 CVD; 291 other causes). Statistically significant graded associations between total WCC, and counts of lymphocytes, monocytes, neutrophils and eosinophils and risk of total mortality were observed. These associations were more apparent in current smokers. Strong associations for all-cause mortality or cancer mortality were observed in subjects with BMI ≥25 kg/m2, ever smoking and elevated WCC (HR 3.92, 95% CI 2.76 to 5.57; HR 3.93, 95% CI 2.30 to 6.72). WCC partly mediated the associations between smoking or BMI and all-cause mortality. CONCLUSIONS:Prediagnostic WCC and its subtypes are associated with all-cause, cancer and CVD mortality risk. It may play a partially mediate role on the association between smoking or obesity and mortality.

In order to explore melanoma risk factors through gender-, age-, race-, and site-specific incidence rates, malignant melanoma cases from the Caucasian whites and non-whites were retrieved from the US SEER database. Age-standardized, age-, and site-specific tumor rates were calculated. All races and both genders showed positive annual average percentage changes (AAPCs) over the years, but AAPCs varied at different body sites, with men's trunk exhibiting the fastest increase. Non-whites were diagnosed at a significantly younger age than whites and showed a trend towards fewer gender differences in the age of diagnosis. However, non-whites and whites showed a similar pattern of age-specific gender differences in the incidence rate ratios. A consistent spiked difference (female vs. male, incidence rate ratio (IRR) >2) was observed at or near the age of 20⁻24 in all race groups and at all body sites. The highest female vs. male IRR was found in the hip and lower extremities, and the lowest IRR was found in the head and neck region in all races. These race-, gender-, and site-dependent differences suggest that age-associated cumulative sun exposure weighs significantly more in late-onset melanomas, while genetics and/or pathophysiological factors make important contributions to early-onset melanomas.

All blood cells (white blood cells [WBC], red blood cells [RBC] and platelets) can play a role in atherosclerosis. Complete blood count (CBC) is widely available in clinical practice but utility as potential risk factors for cardiovascular disease (CVD) is uncertain. Our aim was to assess the associations of pre-diagnostic CBC with incidence of CVD in 14,362 adults free of CVD and aged 47.8 (±11.7) years at baseline, followed-up for 11.4 years (992 incident cases). Cox proportional hazards regressions were used to estimate HRs and 95%CI. Comparing the top (T3) to bottom (T1) tertile, increased total WBC, lymphocyte, monocyte and neutrophil counts were associated with higher CVD risk: 1.31 (1.10; 1.55), 1.20 (1.02; 1.41), 1.21 (1.03; 1.41) and 1.24 (1.05; 1.47), as well as mean corpuscular volume (MCV: 1.23 [1.04; 1.46]) and red cell distribution width (RDW: 1.22 [1.03; 1.44]). Platelets displayed an association for count values above the clinically normal range: 1.49 (1.00; 2.22). To conclude, total and differential WBC count, MCV, RDW and platelet count likely play a role in the aetiology of CVD but only WBC provide a modest improvement for the prediction of 10-year CVD risk over traditional CVD risk factors in a general population.

BackgroundAcute pancreatitis is a potentially lethal disease, with a rising incidence in the Western world. Yet, no pharmacological prevention or specific treatment for acute pancreatitis exists. Also, the connection with severity of acute pancreatitis is unknown. Experimental and epidemiological research suggests a protective effect of angiotensin II receptor blockers.MethodsDuring 2006 to 2008, we performed a nationwide case-control study on Swedish residents aged 40-84 years. First-time cases with acute pancreatitis were identified in the National Patient Register and data on dispensed prescriptions was retrieved from the Prescribed Drug Register. Controls were randomly selected from the general population in Sweden frequency-matched on sex, age, and calendar year. To estimate relative risk of acute pancreatitis, by degree of severity, among users of angiotensin II receptor blockers, as compared to non-users, we used multivariable logistic regression analysis to calculate odds ratios (OR) with 95% confidence interval (CI).ResultsAmong 6,161 cases of acute pancreatitis and 61,637 controls, current use of angiotensin II receptor blockers was followed by a decreased risk of acute pancreatitis, compared to non-users, adjusted OR 0 · 77 (95% CI 0 · 69-0 · 86). No protective association, but an increased risk was found for users of angiotensin-converting enzyme inhibitors (adjusted OR 1 · 11, 95% CI: 1 · 01-1 · 21), analysed for comparison reasons. There was a significant decreased risk associated with both severe acute pancreatitis, (OR 0 · 71 (0 · 59-0 · 85), and mild acute pancreatitis; adjusted OR 0 · 81 (0 · 70-0 · 94).ConclusionThis population-based case-control study indicates that use of angiotensin II receptor blockers might be associated with a lesser risk of acute pancreatitis, and that the protective association was significant among cases of both severe and mild acute pancreatitis.

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.

PurposeVarious food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults.MethodsThis study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders.ResultsMean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant.ConclusionsWe identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.

BackgroundTo assess the role of exogenous estrogen in the etiology of biliary tract cancer, a nationwide population-based cohort study in Sweden was performed.MethodsThe study included all men in Sweden with prostate cancer diagnosed in 1961-2008. Due to treatment standards, patients diagnosed in 1961-1980 were considered more exposed to estrogen, while those diagnosed in 1981-2008 were regarded less exposed. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated to estimate the risk of biliary tract cancer in cohort members compared to the corresponding Swedish male population.ResultsAfter 849 307 person-years of follow-up in 203 131 prostate cancer patients, there were 41 incident gallbladder cancers and 36 cancers of the extra-hepatic bile ducts. In overall, there were no apparent differences in the risk of gallbladder cancer or bile duct cancer between patients diagnosed in 1961-1980 and patients diagnosed in 1981-2008. However, in patients diagnosed in 1961-1980, there was a statistically non-significant increased risk of gallbladder cancer (SIR 1.34; 95% CI 0.71-2.29) and extra-hepatic bile duct cancer (SIR 1.20; 95% CI 0.55-2.28) > 5 years of follow-up after the prostate cancer diagnosis. No such association was found for patients diagnosed in 1981-2008. Sensitivity analyses excluding prostate cancer patients exposed to potential confounding factors did not change the SIRs.ConclusionsLong exposure to high doses of exogenous estrogen might increase the risk of biliary tract cancer. However, any potential excess risk of bile duct cancer resulted by prolonged exposure to high doses of exogenous estrogen seems to be small.

BackgroundThe etiology of small intestinal cancer (SIC) is largely unknown, and there are very few epidemiological studies published to date. No studies have investigated abdominal adiposity in relation to SIC.MethodsWe investigated overall obesity and abdominal adiposity in relation to SIC in the European Prospective Investigation into Cancer and Nutrition (EPIC), a large prospective cohort of approximately half a million men and women from ten European countries. Overall obesity and abdominal obesity were assessed by body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Multivariate Cox proportional hazards regression modeling was performed to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Stratified analyses were conducted by sex, BMI, and smoking status.ResultsDuring an average of 13.9 years of follow-up, 131 incident cases of SIC (including 41 adenocarcinomas, 44 malignant carcinoid tumors, 15 sarcomas and 10 lymphomas, and 21 unknown histology) were identified. WC was positively associated with SIC in a crude model that also included BMI (HR per 5-cm increase = 1.20, 95 % CI 1.04, 1.39), but this association attenuated in the multivariable model (HR 1.18, 95 % CI 0.98, 1.42). However, the association between WC and SIC was strengthened when the analysis was restricted to adenocarcinoma of the small intestine (multivariable HR adjusted for BMI = 1.56, 95 % CI 1.11, 2.17). There were no other significant associations.ConclusionWC, rather than BMI, may be positively associated with adenocarcinomas but not carcinoid tumors of the small intestine.ImpactAbdominal obesity is a potential risk factor for adenocarcinoma in the small intestine.

PurposeThis project sought to test the role of diet-related inflammation in modulating the risk of oesophageal cancer.MethodsA nationwide population-based case-control study was conducted from 1 December 1994 through 31 December 1997 in Sweden. All newly diagnosed patients with adenocarcinoma of the oesophagus or gastroesophageal junction and a randomly selected half of patients with oesophageal squamous cell carcinoma were eligible as cases. Using the Swedish Registry of the Total Population, the control group was randomly selected from the entire Swedish population and frequency-matched on age (within 10 years) and sex. The literature-derived dietary inflammatory index (DII) was developed to describe the inflammatory potential of diet. DII scores were computed based on a food frequency questionnaire. Higher DII scores indicate more pro-inflammatory diets. Odds ratios and 95 % confidence intervals (CI) were computed to assess risk associated between DII scores and oesophageal cancer using logistic regression adjusted by potential confounders.ResultsIn total, 189 oesophageal adenocarcinomas, 262 gastroesophageal junctional adenocarcinomas, 167 oesophageal squamous cell carcinomas, and 820 control subjects were recruited into the study. Significant associations with DII were observed for oesophageal squamous cell carcinoma (ORQuartile4vs1 4.35, 95 % CI 2.24, 8.43), oesophageal adenocarcinoma (ORQuartile4vs1 3.59, 95 % CI 1.87, 6.89), and gastroesophageal junctional adenocarcinoma (ORQuartile4vs1 2.04, 95 % CI 1.24, 3.36). Significant trends across quartiles of DII were observed for all subtypes of oesophageal cancer.ConclusionsDiet-related inflammation appears to be associated with an increased risk of oesophageal cancer, regardless of histological type.

Background/objectivesPolyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort.MethodsDietary data at baseline were collected using a standardized 24-h dietary recall software administered to 36,037 adult subjects. Dietary data were linked with Phenol-Explorer, a database with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing.ResultsMean total polyphenol intake was the highest in Aarhus-Denmark (1786 mg/day in men and 1626 mg/day in women) and the lowest in Greece (744 mg/day in men and 584 mg/day in women). When dividing the subjects into three regions, the highest intake of total polyphenols was observed in the UK health-conscious group, followed by non-Mediterranean (non-MED) and MED countries. The main polyphenol contributors were phenolic acids (52.5-56.9 %), except in men from MED countries and in the UK health-conscious group where they were flavonoids (49.1-61.7 %). Coffee, tea, and fruits were the most important food sources of total polyphenols. A total of 437 different individual polyphenols were consumed, including 94 consumed at a level >1 mg/day. The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers.ConclusionThis study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries.

ObjectiveThis study aimed to assess risk factors for developing marginal ulcer (MU) after gastric bypass (GBP) surgery for obesity.BackgroundMU is a common and potentially serious complication of GBP surgery, little is known about its etiology.MethodsThis population-based cohort study of GBP in 2006-2011 evaluated MU in relation to diabetes, hyperlipidemia, hypertension, chronic obstructive pulmonary disease (COPD), ulcer history, use of proton pump inhibitors (PPIs), aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective serotonin reuptake inhibitors (SSRIs). Multivariable Cox proportional hazard regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for confounding.ResultsAmong 20,294 GBP patients, diabetes and peptic ulcer history entailed statistically significantly increased risk of MU (HR = 1.26, 95% CI 1.03-1.55 and HR  =  2.70, 95% CI 1.81-4.03), although hyperlipidemia, hypertension, and COPD did not. PPI users had an increased HR of MU (HR  =  1.37, 95% CI 1.17-1.60). Aspirin and NSAID consumption less than or equal to median entailed decreased HRs of MU (HR  =  0.56, 95% CI 0.37-0.86 and HR  =  0.30, 95% CI 0.24-0.38), although aspirin and NSAID users more than median had an increased risk and no association with MU, respectively (HR  =  1.90, 95% CI 1.41-2.58 and HR  =  0.90, 95% CI 0.76-1.87). The use of SSRI less than or equal to median had a decreased risk of MU (HR  =  0.50, 95% CI 0.37-0.67), although use more than median entailed increased HR (HR  =  1.26, 95% CI 1.01-1.56).ConclusionsDiabetes and peptic ulcer history seem to be risk factors for MU, but not hyperlipidemia, hypertension, or COPD. Limited doses of aspirin, NSAIDs, and SSRIs might not increase the risk, although higher doses of aspirin do. The association with PPI could be due to confounding by indication.

BackgroundThe role of the metabolic syndrome in the etiology of esophageal and gastric cancer is unclear.MethodsThis was a large nationwide cohort study based on data from 11 prospective population-based cohorts in Norway with long-term follow-up, the Cohort of Norway (CONOR) and the third Nord-Trøndelag Health Study (HUNT3). The metabolic syndrome was assessed by objective anthropometric and metabolic biochemical measures and was defined by the presence of at least three of the following five factors: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, hypertension and high glucose. Newly diagnosed cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma and gastric adenocarcinoma were identified from the Norwegian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders.ResultAmong 192,903 participants followed up for an average of 10.6 years, 62 developed esophageal adenocarcinoma, 64 had esophageal squamous-cell carcinoma and 373 had gastric adenocarcinoma. The metabolic syndrome was significantly associated with an increased risk of gastric adenocarcinoma (HR 1.44, 95% CI 1.14-1.82), but not associated with esophageal adenocarcinoma (HR 1.32, 95% CI 0.77-2.26) or esophageal squamous-cell carcinoma (HR 1.08, 95% CI 0.64-1.83). Increased waist circumference was associated with an increased HR of esophageal adenocarcinoma (HR 2.48, 95% CI 1.27-4.85). No significant association was found between any single component of the metabolic syndrome and risk of esophageal squamous-cell carcinoma. High waist circumference (HR 1.71, 95% CI 1.05-2.80), hypertension (HR 2.41, 95% CI 1.44-4.03) and non-fasting glucose (HR 1.74, 95% CI 1.18-2.56) were also related to an increased risk of gastric adenocarcinoma in women, but not in men.ConclusionMetabolic syndrome was associated with an increased risk of gastric adenocarcinoma in women. Of the individual components of the metabolic syndrome, high waist circumference was positively associated with risk of esophageal adenocarcinoma. Positive associations were also observed for women between high waist circumference, hypertension, high non-fasting glucose and risk of gastric adenocarcinoma. However, further evidence is warranted due to the limited number of cases and the inability to effectively identify gastric cardia adenocarcinoma.

The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.

BackgroundAssociations between type 2 diabetes, anti-diabetic medications and pancreatic cancer are controversial. This study aims to clarify such associations with new-onset type 2 diabetes and repeated measurements of glycated haemoglobin (HbA1c) levels.MethodsA nested case-control study was initiated from the Health Improvement Network (THIN) in UK from 1996 to 2010. Information of pancreatic cancer cases was retrieved electronically from the medical records and manually validated. Control subjects were randomly selected and frequency-matched to the cases on sex, age, and calendar years. Multivariable unconditional logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), and adjusted for potential confounders.ResultsAmong 1,574,768 person-years of follow-up, 529 pancreatic cancer cases and 5000 controls were identified. Type 2 diabetes, or changed HbA1c levels (rather than HbA1c levels at diabetes diagnosis) in diabetes patients (⩾4 mmol mol(-1) compared with

BackgroundThe strong female predominance of biliary tract cancer (BTC) may be related to reproductive factors. We aimed to clarify whether parity or age at first birth influence the risk of BTC.MethodsThis was a population-based, case-control study including Swedish female and male cases of cancer of the gallbladder (GBC), extra hepatic bile ducts (EHCC), or the ampulla of Vater (AVC) between 1960 and 2008. For each case, 10 age- and sex-matched controls were randomly selected. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounders.ResultsIn total, 1169 cases of GBC, 432 cases of EHCC and 295 cases of AVC were included. Multi- and nulliparous women and men had an increased risk of all tumor locations in the biliary tract compared to uniparous women and men, respectively. Whereas higher age at first birth was associated with a decreased risk of GBC in women, no such association was found in men. There were no clear differences in the risk of EHCC and AVC between women and men.ConclusionSex hormones may play a role in the etiology of GBC. The associations between reproductive factors and EHCC and AVC are similar in women and men, which do not support the sex hormone hypothesis.

General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.

Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P difference = .87) and after excluding case patients diagnosed within the first four follow-up years. These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.

Dietary lignans, quercetin and resveratrol have oestrogenic properties, and animal studies suggest that they synergistically decrease cancer risk. A protective effect of lignans on the development of oesophageal cancer in humans has recently been demonstrated, and the present study aimed to test whether these three phytochemicals synergistically decrease the risk of oesophageal cancer. Data from a Swedish nationwide population-based case-control study that recruited 181 cases of oesophageal adenocarcinoma (OAC), 158 cases of oesophageal squamous-cell carcinoma (OSCC), 255 cases of gastro-oesophageal junctional adenocarcinoma (JAC) and 806 controls were analysed. Exposure data were collected through face-to-face interviews and questionnaires. The intake of lignans, quercetin and resveratrol was assessed using a sixty-three-item FFQ. Reduced-rank regression was used to assess a dietary pattern, and a simplified dietary pattern score was categorised into quintiles on the basis of the distribution among the control subjects. Unconditional multivariable logistic regression provided OR with 95% CI, adjusted for all the potential risk factors. A dietary pattern rich in lignans, quercetin and resveratrol was mainly characterised by a high intake of tea, wine, lettuce, mixed vegetables, tomatoes, and whole-grain bread and a low intake of milk. There were dose-dependent associations between simplified dietary pattern scores and all types of oesophageal cancer (all P for trend < 0.05). On comparing the highest quintiles with the lowest, the adjusted OR were found to be 0.24 (95% CI 0.12, 0.49) for OAC, 0.31 (95% CI 0.15, 0.65) for OSCC, and 0.49 (95% CI 0.28, 0.84) for JAC. The results of the present study indicate that a dietary pattern characterised by the intake of lignans, quercetin and resveratrol may play a protective role in the development of oesophageal cancer in the Swedish population.

BackgroundIt is unclear whether concomitant use of clopidogrel and proton-pump inhibitors (PPIs) increases the risk of recurrence of cardiovascular disease or death in patients at high risk of upper gastrointestinal (GI) bleeding.MethodsBased on the Swedish Patient Register, a cohort of cardiovascular disease (including acute myocardial infarction, stroke and angina, from 2006 to 2008) was selected from a population with any diagnosis of upper GI bleeding. Data on drug prescription was retrieved from the Prescribed Drug Register. Patients entered into the cohort after their first discharge for cardiovascular disease and were followed up to death, recurrence of cardiovascular disease, or 90 days. A Cox regression model was conducted and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to evaluate the risks among users of different drug prescriptions.ResultsPatients who were current users of only PPIs (HR 2.02, 95% CI 1.19-3.44), only clopidogrel (HR 1.14, 95% CI 0.53-2.45) and nonusers of both (HR 2.36, 95% CI 1.39-4.00) were at a higher risk of death compared with patients with a concomitant use. Results were similar among 1779 patients who had any history of upper GI bleeding (HR 2.05, 95% CI 1.18-3.54; HR 1.25, 95% CI 0.57-2.72; HR 2.30, 95% CI 1.33-3.98, respectively).ConclusionAmong patients at high risk of upper GI bleeding, those with a concomitant use of PPIs and clopidogrel were at a decreased risk of mortality, and possibly also a decreased risk of recurrence of cardiovascular disease.

BackgroundSex hormones may be associated with colorectal adenocarcinoma, although the association of pregnancy history and risk of colorectal cancer is not consistent.MethodsWe conducted a population-based nested case-control study of persons born between 1932 and 2008 who are in the Swedish Multi-Generation Register. In total, 12,915 women and 15,519 men with colorectal adenocarcinoma were identified during follow-up in the Swedish Cancer Register; 10 age- and sex-matched controls were selected for each case. Number of children and age at first and last birth were analyzed in relation to the risk of colorectal adenocarcinoma, using conditional logistic regression, to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsCompared with women without children, women with 1 or 2 children had an OR of 1.02 (95% CI = 0.93-1.13) of developing adenocarcinoma in the proximal colon; those with 3 or 4 children, 1.18 (1.06-1.32); and those with ≥5 children, 1.30 (1.05-1.61) (test for trend P < 0.01). The corresponding associations in men were 0.92 (0.84-1.00), 1.02 (0.92-1.13), and 0.97 (0.78-1.20), respectively (test for trend P = 0.13).ConclusionsHigher parity in women was associated with the risk of adenocarcinoma of the proximal colon, although not the distal colon or rectum. A similar risk with family size was not seen for fathers. Still, the influence of lifestyle factors cannot be ruled out.

OBJECTIVE: To compare radical surgery with a minimal approach for peptic ulcer bleeding in relation to survival. DESIGN: A Swedish nationwide population-based cohort study from 1987-2008 compared survival after minimal surgery and definitive surgery. The cohort was also stratified into calendar year before and after the year 2000 for subgroup analyses. Data were collected from the Swedish Patient Register. The two surgical groups were matched based on the propensity score to mimic a randomized trial design. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounders. RESULTS: 4,163 patients were included. There were no differences in survival in patients who underwent definitive surgical procedures compared to those who underwent minimal surgery for a bleeding peptic ulcer during the full study period. Using minimal surgery group as the reference, the HRs for death in the definitive surgery group within 30 days, 90 days, 1 year, and 5 years were 0.87 (95% CI 0.72-1.05), 0.93 (0.80-1.09), 1.00 (95% CI 0.87-1.14), and 1.05 (95% CI 0.95-1.16), respectively. The corresponding HRs during the calendar period after the year 2000 were 1.05 (95% CI 0.65-1.69), 1.18 (95% CI 0.81-1.73), 1.17 (0.84-1.62), and 1.27 (95% CI 0.99-1.63), respectively. CONCLUSION: This study found no worse overall survival after minimal surgery compared to more extensive surgery for refractory peptic ulcer bleeding, and indicated better long-term survival in the minimal surgery group during the more recent study period. A minimal approach is probably sufficient in most cases.

ObjectiveThe purpose was to determine whether obesity surgery is associated with a long-term increased risk of colorectal cancer.BackgroundLong-term cancer risk after obesity surgery is not well characterized. Preliminary epidemiological observations and human tissue biomarker studies recently suggested an increased risk of colorectal cancer after obesity surgery.MethodsA nationwide retrospective register-based cohort study in Sweden was conducted in 1980-2009. The long-term risk of colorectal cancer in patients who underwent obesity surgery, and in an obese no surgery cohort, was compared with that of the age-, sex- and calendar year-matched general background population between 1980 and 2009. Obese individuals were stratified into an obesity surgery cohort and an obese no surgery cohort. The standardized incidence ratio (SIR), with 95% confidence interval (CI), was calculated.ResultsOf 77,111 obese patients, 15,095 constituted the obesity surgery cohort and 62,016 constituted the obese no surgery cohort. In the obesity surgery cohort, we observed 70 patients with colorectal cancer, rendering an overall SIR of 1.60 (95% CI 1.25-2.02). The SIR for colorectal cancer increased with length of time after surgery, with a SIR of 2.00 (95% CI 1.48-2.64) after 10 years or more. In contrast, the overall SIR in the obese no surgery cohort (containing 373 colorectal cancers) was 1.26 (95% CI 1.14-1.40) and remained stable with increasing follow-up time.ConclusionsObesity surgery seems to be associated with an increased risk of colorectal cancer over time. These findings would prompt evaluation of colonoscopy surveillance for the increasingly large population who undergo obesity surgery.

BackgroundThe prevalence and role of human papillomavirus (HPV) in the aetiology of oesophageal squamous cell carcinoma is uncertain. Based on the presence of HPV in the oral cavity and its causal association with squamous cell carcinoma of the oropharynx, we hypothesised that HPV is more strongly associated with proximal than distal oesophageal squamous cell carcinoma.MethodsA population-based study comparing HPV infection in relation to tumour site in patients diagnosed with oesophageal squamous cell carcinomas in the Stockholm County in 1999-2006. Multiplex polymerase chain reaction genotyping (PCR) with Luminex was conducted on pre-treatment endoscopic biopsies to identify type specify HPV. Carcinogenic activity of HPV was assessed by p16(INK4a) expression. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals.ResultsAmong 204 patients, 20 (10%) had tumours harbouring HPV DNA, almost all (90%) of HPV high-risk type, mainly HPV16. Tumours containing HPV were not overrepresented in the upper compared to the middle or lower third of the oesophagus (odds ratio 0.6, 95% confidence interval 0.2-1.9). P16(INK4a) expression was similarly common (24% and 16%) in the HPV-positive and HPV-negative groups.ConclusionThis study found a limited presence of HPV in oesophageal squamous cell carcinoma of uncertain oncogenic relevance and did not demonstrate that HPV was more strongly associated with proximal than distal tumours.