Demetrius Albanes

High processed meat consumption is a risk factor of type 2 diabetes in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study

Relatively small lifestyle modifications related to weight reduction, physical activity and diet have been shown to decrease the risk of type 2 diabetes. Connected with diet, low consumption of meat has been suggested as a protective factor of diabetes. The aim of the present study was to examine the association between the consumption of total meat or the specific types of meats and the risk of type 2 diabetes. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort included middle-aged male smokers. Up to 12 years of follow-up, 1098 incident cases of diabetes were diagnosed from 24 845 participants through the nationwide register. Food consumption was assessed by a validated FFQ. In the age- and intervention group-adjusted model, high total meat consumption was a risk factor of type 2 diabetes (relative risk (RR) 1.50, 95 % CI 1.23, 1.82, highest v. lowest quintile). The result was similar after adjustment for environmental factors and foods related to diabetes and meat consumption. The RR of type 2 diabetes was 1.37 for processed meat (95 % CI 1.11, 1.71) in the multivariate model. The results were explained more by intakes of Na than by intakes of SFA, protein, cholesterol, haeme Fe, Mg and nitrate, and were not modified by obesity. No association was found between red meat, poultry and the risk of type 2 diabetes. In conclusion, reduction of the consumption of processed meat may help prevent the global epidemic of type 2 diabetes. It seems like Na of processed meat may explain the association.

Association of Seropositivity to Helicobacter Species and Biliary Tract Cancer in the ATBC Study

Helicobacter have been detected in human bile and hepatobiliary tissue. Despite evidence that Helicobacter species promote gallstone formation and hepatobiliary tumors in laboratory studies, it remains unclear whether Helicobacter species contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to 15 Helicobacter pylori proteins was associated with subsequent incidence of hepatobiliary cancers in the Finnish Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study. We included 64 biliary cancers, 122 liver cancers, and 224 age‐matched controls which occurred over the course of 22 years. Helicobacter pylori seropositivity was defined as those positive to ≥4 antigens. Odds ratios (OR) and 95% confidence intervals were adjusted for major hepatobiliary cancer risk factors. Among the controls, 88% were seropositive to H. pylori at baseline. Among those who subsequently developed hepatobiliary cancer, the prevalence of seropositivity was higher: 100% for gallbladder cancer, 97% of extrahepatic bile duct cancer, 91% of ampula of Vater cancer, 96% of intrahepatic bile duct cancer, and 94% of hepatocellular carcinoma. Although the OR for gallbladder cancer could not be calculated, the OR for the other sites were 7.01 (95% confidence interval [CI]: 0.79‐62.33), 2.21 (0.19‐25.52), 10.67 (0.76‐150.08), and 1.20 (0.42‐3.45), respectively, with an OR of 5.47 (95% CI: 1.17‐25.65) observed for the biliary tract cancers combined. ORs above 1 were observed for many of the investigated antigens, although most of these associations were not statistically significant. Conclusion: Seropositivity to H. pylori proteins was associated with an increased risk of biliary tract cancers in ATBC. Further studies are needed to confirm our findings and to determine how H. pylori might influence the risk of biliary tract cancer. (Hepatology 2014;60:1962–1970)

Vitamin D- binding protein, circulating vitamin D and risk of renal cell carcinoma

Cell culture experiments suggest that vitamin D may inhibit renal carcinogenesis, but human studies of circulating 25‐hydroxyvitamin D [25(OH)D], the accepted measure of vitamin D status, and kidney cancer have been null. Limited research has examined the role of circulating vitamin D‐binding protein (DBP) in the association between 25(OH)D and disease risk, and it is unclear whether free 25(OH)D in circulation is a better measure of effective exposure, or if DBP may independently impact outcomes. We conducted a nested case–control analysis within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study to examine whether circulating DBP concentration was prospectively associated with risk of renal cell carcinoma, and whether it modified the association with 25(OH)D. Renal cell carcinoma cases (n = 262) were matched 1:1 to controls on age (±1 year) and date of blood collection (± 30 days). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of renal cell carcinoma risk by quartiles of 25(OH)D, DBP and the molar ratio of 25(OH)D:DBP, a proxy for free circulating 25(OH)D. Men with higher DBP concentrations were at significantly decreased risk of kidney cancer (Q4 vs. Q1: OR = 0.17, 95% CI = 0.08–0.33; p‐trend < 0.0001), a finding unchanged by adjustment for 25(OH)D. Although we observed no association with total 25(OH)D, we found slightly increased risk with higher levels of estimated free 25(OH)D [Q4 vs. Q1 of the 25(OH)D:DBP ratio, OR = 1.61, 95% CI = 0.95–2.73; p‐trend = 0.09]. The strong protective association observed between higher circulating DBP concentration and kidney cancer risk requires replication but suggests a vitamin D‐independent influence of DBP.

Low vitamin B-12 increases risk of gastric cancer: A prospective study of one-carbon metabolism nutrients and risk of upper gastrointestinal tract cancer

Previous studies have found associations between one‐carbon metabolism nutrients and risk of several cancers, but little is known regarding upper gastrointestinal tract (UGI) cancer. We analyzed prediagnostic serum concentrations of several one‐carbon metabolism nutrients (vitamin B12, folate, vitamin B6, riboflavin and homocysteine) in a nested case–control study within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988. We conducted a nested case–control study including 127 noncardia gastric adenocarcinoma (NCGA), 41 esophagogastric junctional adenocarcinoma and 60 esophageal squamous cell carcinoma incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection and follow‐up time. One‐carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to cancer diagnosis). Odds ratios and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower prediagnostic vitamin B12 concentrations at baseline were associated with a 5.8‐fold increased risk of NCGA (95% CIu2009=u20092.7–12.6 for lowest compared to highest quartile, p‐trend <0.001). This association remained in participants who developed cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum vitamin B12 (>300 pmol/L). In contrast, pepsinogen I, a known serologic marker of gastric atrophy, was not associated with NCGA in this population. As vitamin B12 absorption requires intact gastric mucosa to produce acid and intrinsic factor, our findings suggest vitamin B12 as a possible serologic marker for the atrophic gastritis that precedes NCGA, one more strongly associated with subsequent NCGA than pepsinogen.

A prospective analysis of telomere length and pancreatic cancer in the alpha-tocopherol beta-carotene cancer (ATBC) prevention study

Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length maintenance. To test whether telomere length is associated with pancreatic cancer risk, we conducted a nested case–control study in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50–69 years at baseline. Between 1992 and 2004, 193 incident cases of pancreatic adenocarcinoma occurred (mean follow‐up from blood draw: 6.3 years) among participants with whole blood samples available for telomere length assays. For these cases and 660 controls, we calculated odds ratios (OR) and 95% confidence intervals using unconditional logistic regression, adjusting for age, number of years smoked regularly, and history of diabetes mellitus. Telomere length was categorized into quartiles (shortest to longest) and analyzed as both a categorical and a continuous normal variable (reported per 0.2 unit increase in telomere length). All statistical tests were two‐sided. Longer telomere length was significantly associated with increased pancreatic cancer risk (continuous OR = 1.26 95% CI = 1.09–1.46; highest quartile compared to lowest, OR = 1.57, 95% CI = 1.01–2.43, p‐trend = 0.007). This association remained for subjects diagnosed within the first five years of blood draw (continuous OR = 1.46, 95% CI = 1.19–1.79 highest quartile OR = 2.92, 95% CI = 1.47–5.77, p‐trend = 0.002), but not those diagnosed greater than five years after blood draw (continuous OR = 1.03, 95% CI = 0.85–1.22; highest quartile OR = 1.04, 95% CI = 0.60–1.79). This is the first prospective study to suggest an association between longer blood leukocyte telomere length and increased pancreatic cancer risk.