G. Berglund

Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study

Abstract Objectives To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death. Design Nested case-control study within the European prospective investigation into cancer and nutrition (EPIC). Participants 303 020 people from the EPIC cohort (total 500 000) who had never smoked or who had stopped smoking for at least 10 years, 123 479 of whom provided information on exposure to environmental tobacco smoke. Cases were people who developed respiratory cancers or died from respiratory conditions. Controls were matched for sex, age (plus or minus 5 years), smoking status, country of recruitment, and time elapsed since recruitment. Main outcome measures Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people. Results Over seven years of follow up, 97 people had newly diagnosed lung cancer, 20 had upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema. In the whole cohort exposure to environmental tobacco smoke was associated with increased risks (hazard ratio 1.30, 95% confidence interval 0.87 to 1.95, for all respiratory diseases; 1.34, 0.85 to 2.13, for lung cancer alone). Higher results were found in the nested case-control study (odds ratio 1.70, 1.02 to 2.82, for respiratory diseases; 1.76, 0.96 to 3.23, for lung cancer alone). Odds ratios were consistently higher in former smokers than in those who had never smoked; the association was limited to exposure related to work. Cotinine concentration was clearly associated with self reported exposure (3.30, 2.07 to 5.23, for detectable/non-detectable cotinine), but it was not associated with the risk of respiratory diseases or lung cancer. Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood (hazard ratio 3.63, 1.19 to 11.11, for daily exposure for many hours). Conclusions This large prospective study, in which the smoking status was supported by cotinine measurements, confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases, particularly in ex-smokers.

Long-term weight change and breast cancer risk: the European prospective investigation into cancer and nutrition (EPIC)

We examined prospectively the association between weight change during adulthood and breast cancer risk, using data on 1358 incident cases that developed during 5.8 years of follow-up among 40u2009429 premenopausal and 57u2009923 postmenopausal women from six European countries, taking part in the European prospective investigation into cancer and nutrition study. Multivariate Cox regression models were used to calculate hazard ratios according to weight change (kg), defined as the weight difference between age at enrolment and age 20 adjusted for other risk factors. Changes in weight were not associated with premenopausal breast cancer risk. In postmenopausal women, weight gain was positively associated with breast cancer risk only among noncurrent hormone replacement therapy (HRT) users (P-trend ⩽0.0002). Compared to women with a stable weight (±2u2009kg), the relative risk for women who gained 15–20u2009kg was 1.50 (95% confidence interval (CI) 1.06–2.13). The pooled RR per weight gain increment of 5u2009kg was 1.08 (95% CI 1.04–1.12). Weight gain was not associated with breast cancer risk in current HRT users, although, overall, these women experienced a much higher risk of breast cancer compared with nonusers. Our findings suggest that large adult weight gain was a significant predictor of breast cancer in postmenopausal women not taking exogenous hormones.

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

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 α- and γ-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 α-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 β-cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30–0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22–0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33–0.93, Ptrend=0.005) and lipid-unadjusted α-tocopherol (OR=0.59, 95% CI=0.37–0.94, Ptrend=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 α-tocopherol (OR=0.26, 95% CI=0.11–0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and α-tocopherol are associated with reduced risk of GC.

Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST).

BACKGROUNDnThe relative contribution to gastric cancer (GC) risk of variants in genes that determine the inflammatory response remains mostly unknown and results from genotyping studies are inconsistent.nnnPATIENTS AND METHODSnA nested case-control study within the prospective European Prospective Investigation into Cancer and Nutrition cohort was carried out, including 248 gastric adenocarcinomas and 770 matched controls. Twenty common polymorphisms at cytokine genes [interleukin (IL)1A, IL1B, IL1RN, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, lymphotoxin alpha and tumor necrosis factor (TNF)] were analyzed. Antibodies against Helicobacter pylori (Hp) and CagA were measured.nnnRESULTSnIL1RN 2R/2R genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19-4.96] and allele IL1RN Ex5-35C were associated with an increased risk of Hp(+) non-cardia GC. IL8 -251AA genotype was associated with a decreased risk of Hp(+) non-cardia GC (OR 0.51; 95% CI 0.32-0.81), mainly of the intestinal type. These associations were not modified by CagA status. Carriers of IL1B -580C and TNF -487A alleles did not associate with an increased risk. A moderately increased risk of Hp(+) non-cardia GC for IL4R -29429T variant was observed (OR 1.74; 95% CI 1.15-2.63).nnnCONCLUSIONnThis prospective study confirms the association of IL1RN polymorphisms with the risk of non-cardia GC and indicates that IL8 -251T>A may modify the risk for GC.

Fasting blood glucose in determining the prevalence of diabetes in a large, homogeneous population of Caucasian middle‐aged women

Abstract. Objectives. To determine the usefulness of a single, fasting blood glucose (FBG) value in measuring the prevalence of diabetes mellitus in a large, homogeneous population.

Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?

BackgroundThe suspect carcinogens, heterocyclic amines (HAAs), found in well-done meat require host-mediated metabolic activation before inducing DNA mutations. The role of SULT1A1 and of NAT2 on the activation of HAAs suggests that NAT2 rapid acetylator genotype and SULT1A1 allele variants can have an effect on HAA carcinogenicity.MethodsData were collected as part of a case–control study nested within the EPIC cohort, the Gen Air investigation. EPIC is a prospective study designed to investigate the relationship between nutrition and cancer. Information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire. The subjects were restricted to non-smokers. We calculated the matched odds ratio for bladder cancer risk using logistic regression, controlling for potential confounders.ResultsThere were 227 bladder cases and 612 controls matched 1:3. Meat intake and NAT2 genotype were not independently associated with bladder cancer risk. A significant relationship was observed between bladder cancer risk and consumption of meat only among subjects with the rapid NAT2 genotype (odds ratios [OR] 2.9, 95% CI 1.0–7.9 for the 2nd quartile of meat intake; 3.6, 95% CI 1.3–9.7 for the 3rd quartile; and 3.5, 95% CI 1.2–9.7 for the 4th quartile), and was not present among subjects with the slow genotype. An interaction between NAT2 and meat intake was found in logistic regression (Pxa0=xa00.034). No association was observed for SULT1A *1/2 genotype (1.0; 95% CI 0.7–1.5) and for SULT1A1 *2/2 genotype (0.9; 95% CI 0.5–1.7).ConclusionsThese results are suggestive of a role of meat intake and NAT2 on bladder cancer risk. They support the hypothesis that among subjects with the rapid NAT2 acetylation genotype higher levels of HAAs exposure are a bladder cancer risk factor. We did not observe an effect of SULT1A1 allele variants on this cancer. The present study adds new information on the possible long-term adverse effects of diets with high meat intake.

Habitual dietary intake versus glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women

Abstract. Larsson H, Elmståhl S, Berglund G, Ahrén B (Lund University, Malmö University Hospital, Malmö, Sweden). Habitual dietary intake versus glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women. J Intern Med;245: 581–591.

Meat intake and bladder cancer in a prospective study: A role for heterocyclic aromatic amines? (Cancer Causes and Control DOI: 10.1007/s10552-008-9121-1)

B. Lumbreras Æ S. Garte Æ K. Overvad Æ A. Tjonneland Æ F. Clavel-Chapelon Æ J. P. Linseisen Æ H. Boeing Æ A. Trichopoulou Æ D. Palli Æ M. Peluso Æ V. Krogh Æ R. Tumino Æ S. Panico Æ H. B. Bueno-De-Mesquita Æ P. H. Peeters Æ E. Lund Æ C. Martinez Æ M. Dorronsoro Æ A. Barricarte Æ M. D. Chirlaque Æ J. R. Quiros Æ G. Berglund Æ G. Hallmans Æ N. E. Day Æ T. J. Key Æ R. Saracci Æ R. Kaaks Æ C. Malaveille Æ P. Ferrari Æ P. Boffetta Æ T. Norat Æ E. Riboli Æ C. A. Gonzalez Æ P. Vineis

Erratum: Amount of DNA in plasma and cancer risk: A prospective study (International Journal of Cancer (2004) 111 (746-749))

Gormally E, Hainaut P, Caboux E, Airoldi L, Autrup H, Malaveille C, Dunning A, Garte S, Matullo G, Overvad K, Tjonneland A, Clavel-Chapelon F, Boffetta P, Boeing H, Trichopoulou A, Palli D, Krogh V, Tumino R, Panico S, Bueno-De-Mesquita HB, Peeters PH, Lund E, Gonzalez CA, Martinez C, Dorronsoro M, Barricarte A, Tormo MJ, Quiros JR, Berglund G, Hallmans G, Day NE, Key TJ, Veglia F, Peluso M, Norat T, Saracci R, Kaaks R, Riboli E, Vineis P. Amount of DNA in plasma and cancer risk: A prospective study. Int. J. Cancer, 111, 746–749 (2004).