• Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study.

      Buckland, Genevieve; Agudo, Antonio; Luján, Leila; Jakszyn, Paula; Bueno-de-Mesquita, H. Bas; Palli, Domenico; Boeing, Heiner; Carneiro, Fátima; Krogh, Vittorio; Sacerdote, Carlotta; et al. (2010-02)
      BACKGROUND: The Mediterranean dietary pattern is believed to protect against cancer, although evidence from cohort studies that have examined particular cancer sites is limited. OBJECTIVE: We aimed to explore the association between adherence to a relative Mediterranean diet (rMED) and incident gastric adenocarcinoma (GC) within the European Prospective Investigation into Cancer and Nutrition study. DESIGN: The study included 485,044 subjects (144,577 men) aged 35-70 y from 10 European countries. At recruitment, dietary and lifestyle information was collected. An 18-unit rMED score, incorporating 9 key components of the Mediterranean diet, was used to estimate rMED adherence. The association between rMED and GC with respect to anatomic location (cardia and noncardia) and histologic types (diffuse and intestinal) was investigated. A calibration study in a subsample was used to control for dietary measurement error. RESULTS: After a mean follow-up of 8.9 y, 449 validated incident GC cases were identified and used in the analysis. After stratification by center and age and adjustment for recognized cancer risk factors, high compared with low rMED adherence was associated with a significant reduction in GC risk (hazard ratio: 0.67; 95% CI: 0.47, 0.94). A 1-unit increase in the rMED score was associated with a decreased risk of GC of 5% (95% CI: 0.91, 0.99). There was no evidence of heterogeneity between different anatomic locations or histologic types. The calibrated results showed similar trends (overall hazard ratio for GC: 0.93; 95% CI: 0.89, 0.99). CONCLUSION: Greater adherence to an rMED is associated with a significant reduction in the risk of incident GC.
    • Aromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort.

      Agudo, Antonio; Peluso, Marco; Sala, Nuria; Capella, Gabriel; Munnia, Armelle; Piro, Sara; Marin, Fatima; Ibanez, Raquel; Amiano, Pilar; Tormo, M. Jose; et al. (2009-06)
      Aromatic compounds such as polycyclic aromatic hydrocarbons, arylamines and heterocyclic amines require metabolic activation to form metabolites able to bind to DNA, a process mediated by polymorphic enzymes. We measured aromatic DNA adducts in white blood cells by the (32)P-post-labelling assay in a sample of 296 healthy adults (147 men and 149 women) from five regions of Spain. We also analyzed functional polymorphisms in the metabolic genes CYP1A1, CYP1A2, EPHX1, GSTM1, GSTT1, NAT2 and SULT1A1. A significant increased level of DNA aromatic adducts was found related to the fast oxidation-hydrolysis phenotype defined by the polymorphism I462V in CYP1A1, the allele A in IVS1-154C>A of CYP1A2 and the combination Tyrosine-Arginine for Y113H and H139R of EPHX1. Geometric means (adducts per 10(-9) normal nucleotides) were 2.17, 4.04 and 6.30 for slow, normal and fast phenotypes, respectively (P-trend = 0.01). Slow acetylation by NAT2 was associated with a significant decrease in adduct level; subjects with slow alleles *5A and *7A/B had in average 1.56 x 10(-9)adducts, as compared with 5.60 for those with normal NAT2 activity (P-value = 0.01). No association was seen with polymorphisms of other metabolic genes such as GSTM1, GSTT1 or SULT1A1. We concluded that the metabolic pathways of oxidation, hydrolysis and acetylation are relevant to the formation of bulky DNA adducts. This could suggest a potential involvement of aromatic compounds in the formation of such adducts; however, given lack of specificity of the post-labeling assay, a firm conclusion cannot be drawn.
    • The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European Prospective Investigation into Cancer and Nutrition.

      Vollset, Stein Emil; Igland, Jannicke; Jenab, Mazda; Fredriksen, Ase; Meyer, Klaus; Eussen, Simone; Gjessing, Hakon K.; Ueland, Per Magne; Pera, Guillem; Sala, Nuria; et al. (2007-11)
      Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospective study of blood folate levels and gastric cancer. Gastric cancer cases (n=247) and controls (n=631) were matched for study center, age, sex, and time of blood donation. Two common single nucleotide polymorphisms of the MTHFR gene were determined, as were plasma concentrations of folate, cobalamin (vitamin B12), total homocysteine, and methylmalonic acid (cobalamin deficiency marker) in prediagnostic plasma. Risk measures were calculated with conditional logistic regression. Although no relations were observed between plasma folate or total homocysteine concentrations and gastric cancer, we observed a trend toward lower risk of gastric cancer with increasing cobalamin concentrations (odds ratio, 0.79 per SD increase in cobalamin; P=0.01). Further analyses showed that the inverse association between cobalamin and gastric cancer was confined to cancer cases with low pepsinogen A levels (marker of severe chronic atrophic gastritis) at the time of blood sampling. The 677 C-->T MTHFR polymorphism was not associated with gastric cancer, but we observed an increased risk with the variant genotype of the 1298 A-->C polymorphism (odds ratio, 1.47 for CC versus AA; P=0.04). In conclusion, we found no evidence of a role of folate in gastric cancer etiology. However, we observed increased gastric cancer risk at low cobalamin levels that was most likely due to compromised cobalamin status in atrophic gastritis preceding gastric cancer.
    • Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects.

      Ricceri, Fulvio; Godschalk, Roger W.; Peluso, Marco; Phillips, David H.; Agudo, Antonio; Georgiadis, Panagiotis; Loft, Steffen; Tjonneland, Anne; Raaschou-Nielsen, Ole; Palli, Domenico; et al. (2010-12)
      Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants.
    • Cereal fiber intake may reduce risk of gastric adenocarcinomas: the EPIC-EURGAST study.

      Mendez, Michelle A.; Pera, Guillem; Agudo, Antonio; Bueno-de-Mesquita, H. Bas; Palli, Domenico; Boeing, Heiner; Carneiro, Fatima; Berrino, Franco; Sacerdote, Carlotta; Tumino, Rosario; et al. (2007-10-01)
      Numerous case-control studies suggest dietary fiber may reduce risk of gastric cancer, but this has not been confirmed prospectively. A previous case-control study reported reduced risk of gastric cardia adenocarcinomas associated with cereal fiber, but not with fruit or vegetable fiber. To date, different food sources of fiber have not been examined with respect to noncardia tumors or diverse histologic sub-types. This study prospectively examines associations between fiber from different food sources and incident gastric adenocarcinomas (GC) among more than 435,000 subjects from 10 countries participating in the European Prospective Investigation into Cancer and Nutrition study. Subjects aged 25-70 years completed dietary questionnaires in 1992-98, and were followed up for a median of 6.7 years. About 312 incident GCs were observed. The relative risk of GC was estimated based on cohort-wide sex-specific fiber intake quartiles using proportional hazards models to estimate hazards ratios (HRs) and 95% confidence intervals (CIs). Intakes of cereal fiber, but not total, fruit or vegetable fiber, were associated with reduced GC risk [adjusted HR for the highest vs. lowest quartile of cereal fiber 0.69, 0.48-0.99]. There was a strong inverse association for diffuse [HR 0.43, 0.22-0.86], but not intestinal type [HR 0.98, 0.54-1.80] tumors. Associations for cardia vs. noncardia tumors were similar to those for overall GC, although cardia associations did not reach significance. Cereal fiber consumption may help to reduce risk of GC, particularly diffuse type tumors. Further study on different food sources of fiber in relation to GC risk is warranted to confirm these relationships.
    • DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study.

      Capella, Gabriel; Pera, Guillem; Sala, Nuria; Agudo, Antonio; Rico, Francisco; Del Giudicce, Giuseppe; Plebani, Mario; Palli, Domenico; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; et al. (2008-12)
      BACKGROUND: The contribution of genetic variation in DNA repair genes to gastric cancer (GC) risk remains essentially unknown. The aim of this study was to explore the relative contribution of DNA repair gene polymorphisms to GC risk and severe chronic atrophic gastritis (SCAG). Method A nested case control study within the EPIC cohort was performed including 246 gastric adenocarcinomas and 1175 matched controls. Controls with SCAG (n = 91), as defined by low pepsinogen A (PGA) levels, and controls with no SCAG (n = 1061) were also compared. Twelve polymorphisms at DNA repair genes (MSH2, MLH1, XRCC1, OGG1 and ERCC2) and TP53 gene were analysed. Antibodies against Helicobacter pylori were measured. RESULTS: No association was observed for any of these polymorphisms with stomach cancer risk. However, ERCC2 K751Q polymorphism was associated with an increased risk for non-cardial neoplasm [odds ratio (OR) = 1.78; 95% confidence interval (CI) 1.02-3.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR = 2.0; 95% CI 1.09-3.65) and K751Q alleles (OR = 1.82; 95% CI 1.01-3.30) and XRCC1 R399Q (OR = 1.69; 95% CI 1.02-2.79) allele were associated with an increased risk for SCAG. CONCLUSION: Our study supports a role of ERCC2 in non-cardial GC but not in cardial cancer. A concordant result was observed for subjects with low PGA levels. XRCC1 allele was associated also with SCAG. This is the first prospective study suggesting that individual variation in DNA repair may be relevant for gastric carcinogenesis, a finding that will require further confirmation validation in larger independent studies.
    • Fruit and vegetable intakes, dietary antioxidant nutrients, and total mortality in Spanish adults: findings from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain).

      Agudo, Antonio; Cabrera, Laia; Amiano, Pilar; Ardanaz, Eva; Barricarte, Aurelio; Berenguer, Toni; Chirlaque, Maria D.; Dorronsoro, Miren; Jakszyn, Paula; Larranaga, Nerea; et al. (2007-06)
      BACKGROUND: Epidemiologic data suggest that persons with diets rich in fruit and vegetables are at a lower risk of several chronic diseases and mortality than are persons with diets poor in fruit and vegetables. Often, this effect is attributed to antioxidant micronutrients found in plant foods. OBJECTIVE: We aimed to assess the relation of mortality to the consumption of fruit, vegetables, and other plant foods and to the dietary intake of vitamin C, vitamin E, and carotenoids. DESIGN: The study was a prospective study in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition. During 6.5 y of follow-up, 562 deaths occurred in 41 358 subjects aged 30-69 y. Proportional hazards regression analysis was used to assess the relation between dietary factors and total mortality. RESULTS: After adjustment for age, sex, and several potential confounders, the hazard ratio for the highest versus the lowest quartile of consumption was 0.79 (95% CI: 0.62, 1.00; P for trend = 0.029) for fresh fruit, 0.72 (0.56, 0.91; P for trend = 0.006) for root vegetables, and 0.77 (0.60, 0.98; P for trend = 0.015) for fruiting vegetables (ie, vegetables that contain the "fruit" part of the plant, the seeds). The corresponding figures for antioxidant nutrients were 0.74 (0.58, 0.94; P for trend = 0.009) for vitamin C, 0.68 (0.53, 0.87; P for trend = 0.006) for provitamin A carotenoids, and 0.65 (0.51, 0.84; P for trend 0.001) for lycopene. The effect of vitamin C and provitamin A disappeared after adjustment for total antioxidant capacity in plant foods. CONCLUSIONS: A high intake of fresh fruit, root vegetables, and fruiting vegetables is associated with reduced mortality, probably as a result of their high content of vitamin C, provitamin A carotenoids, and lycopene. Antioxidant capacity could partly explain the effect of ascorbic acid and provitamin A but not the association with lycopene.
    • Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study.

      Vineis, Paolo; Hoek, Gerard; Krzyzanowski, Michal; Vigna-Taglianti, Federica; Veglia, Fabrizio; Airoldi, Luisa; Overvad, Kim; Raaschou-Nielsen, Ole; Clavel-Chapelon, Francoise; Linseisen, Jacob; et al. (2007)
      BACKGROUND: Several countries are discussing new legislation on the ban of smoking in public places, and on the acceptable levels of traffic-related air pollutants. It is therefore useful to estimate the burden of disease associated with indoor and outdoor air pollution. METHODS: We have estimated exposure to Environmental Tobacco Smoke (ETS) and to air pollution in never smokers and ex-smokers in a large prospective study in 10 European countries (European Prospective Investigation into Cancer and Nutrition)(N = 520,000). We report estimates of the proportion of lung cancers attributable to ETS and air pollution in this population. RESULTS: The proportion of lung cancers in never- and ex-smokers attributable to ETS was estimated as between 16 and 24%, mainly due to the contribution of work-related exposure. We have also estimated that 5-7% of lung cancers in European never smokers and ex-smokers are attributable to high levels of air pollution, as expressed by NO2 or proximity to heavy traffic roads. NO2 is the expression of a mixture of combustion (traffic-related) particles and gases, and is also related to power plants and waste incinerator emissions. DISCUSSION: We have estimated risks of lung cancer attributable to ETS and traffic-related air pollution in a large prospective study in Europe. Information bias can be ruled out due to the prospective design, and we have thoroughly controlled for potential confounders, including restriction to never smokers and long-term ex-smokers. Concerning traffic-related air pollution, the thresholds for indicators of exposure we have used are rather strict, i.e. they correspond to the high levels of exposure that characterize mainly Southern European countries (levels of NO2 in Denmark and Sweden are closer to 10-20 ug/m3, whereas levels in Italy are around 30 or 40, or higher).Therefore, further reduction in exposure levels below 30 ug/m3 would correspond to additional lung cancer cases prevented, and our estimate of 5-7% is likely to be an underestimate. Overall, our prospective study draws attention to the need for strict legislation concerning the quality of air in Europe.
    • Occupational exposures contribute to educational inequalities in lung cancer incidence among men: Evidence from the EPIC prospective cohort study.

      Menvielle, Gwenn; Boshuizen, Hendriek; Kunst, Anton E.; Vineis, Paolo; Dalton, Susanne O.; Bergmann, Manuela M.; Hermann, Silke; Veglia, Fabrizio; Ferrari, Pietro; Overvad, Kim; et al. (2010-04-15)
      The aim of this study is to investigate to what extent occupational exposures may explain socioeconomic inequalities in lung cancer incidence after adjusting for smoking and dietary factors. Analyses were based on a subsample of the European Prospective Investigation into Cancer and Nutrition (EPIC study), a prospective cohort. The analyses included 703 incident lung cancer cases among men in Denmark, the United Kingdom, Germany, Italy, Spain and Greece. The socioeconomic position was measured using the highest level of education. The estimates of relative indices of inequality (RII) were computed with Cox regression models. We first adjusted for smoking (with detailed information on duration and quantity) and dietary factors (fruits and vegetables consumption) and then for occupational exposures. The exposure to three carcinogens [asbestos, heavy metals and polycyclic aromatic hydrocarbons (PAH)] was analyzed. The occupational exposures explained 14% of the socioeconomic inequalities remaining after adjustment for smoking and fruits and vegetables consumption. The inequalities remained nevertheless statistically significant. The RII decreased from 1.87 (95% CI: 1.36-2.56) to 1.75 (1.27-2.41). The decrease was more pronounced when adjusting for asbestos than for heavy metals or PAH. Analyses by birth cohort suggested an effect of occupational exposures among older men, while due to small number of endpoints, no conclusion could be drawn about the role of occupational exposures in educational inequalities among younger men. Our study revealed that the impact of occupational exposures on socioeconomic inequalities in cancer incidence, rarely studied until now, exists while of modest magnitude.
    • Polychlorinated biphenyls in Spanish adults: determinants of serum concentrations.

      Agudo, Antonio; Goni, Fernando; Etxeandia, Arsenio; Vives, Asuncion; Millan, Esmeralda; Lopez, Raul; Amiano, Pilar; Ardanaz, Eva; Barricarte, Aurelio; Chirlaque, M. Dolores; et al. (2009-07)
      BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent compounds that may pose an environmental hazard to humans, food being the main source of exposure for the general population. OBJECTIVE: To measure the serum concentrations of the main PCBs in subjects from the general population in Spain, and to assess potential determinants of such concentrations. METHODS: Serum was obtained from blood samples of 953 subjects aged 35-64 years, residents in five Spanish regions (three from the North and two from the South), randomly selected from the EPIC-Spain cohort. Blood collection took place during 1992-1996 and four PCB congeners (118, 138, 153 and 180) were determined by means of gas chromatography with electron-capture detection (GC-ECD). RESULTS: The concentration of total PCBs was 459 ng/g lipids (or 3.1 microg/l); the corresponding figures for PCB 153 were 186 ng/g lipids and 1.25 microg/l. Men had higher values than women, PCB levels increased with age, and serum concentration of PCBs was higher in northern regions. Body mass index (BMI) was inversely related to PCB concentrations, and fish intake was the dietary factor showing the greatest association with serum PCBs. The pattern described was similar for each congener separately. CONCLUSIONS: We found concentrations similar to those reported in European countries where blood collection was carried during the same period. Regional differences within Spain are not fully explained by anthropometric or dietary factors. The inverse association with BMI suggests that in the mid-1990s there was still ongoing or recent exposure to PCBs in Spain.
    • Pooled analysis of studies on DNA adducts and dietary vitamins.

      Ragin, Camille; Minor, Aerie; Agudo, Antonio; Farmer, Peter; Garte, Seymour; Gonzales, Carlos; Kalina, Ivan; Matullo, Giuseppe; Popov, Todor; Palli, Domenico; et al. (2010-10)
      OBJECTIVES: There is some evidence that dietary components that are rich in antioxidant and vitamins are inversely associated with DNA adduct levels induced by environmental carcinogens such as polycyclic aromatic hydrocarbons, although the epidemiologic data are inconsistent. This study addresses the association between vitamins, DNA adducts and smoking. METHODS: A combined analysis of individual data on the association between bulky DNA adducts and dietary vitamins was conducted. A Medline search was performed to identify studies on healthy subjects in which smoking and vitamins intake information were available, and bulky DNA adducts were measured in peripheral blood with 32P-postlabelling. Eight published studies met the eligibility criteria, and individual data from 7 data sets including 2758 subjects were obtained. GSTM1 and GSTT1 were also available on all the subjects. RESULTS: Vitamin E was inversely significantly associated with DNA adducts after adjustment for possible confounding factors. Vitamins A and C were not independent predictors of DNA adducts. A stratified analysis showed that vitamin A had a significant inverse association with DNA adducts in ever smokers only. CONCLUSIONS: This result is relevant to planning any future chemo-preventive interventions directed to high risk subgroups of the population, for cancer prevention.
    • Prospective study of physical activity and risk of primary adenocarcinomas of the oesophagus and stomach in the EPIC (European Prospective Investigation into Cancer and nutrition) cohort.

      Huerta, Jose Maria; Navarro, Carmen; Chirlaque, Maria-Dolores; Tormo, Maria-Jose; Steindorf, Karen; Buckland, Genevieve; Carneiro, Fatima; Johnsen, Nina Fons; Overvad, Kim; Stegger, Jakob; et al. (2010-05)
      OBJECTIVE: To analyse the association between types of physical activity (occupational, recreational and household, vigorous and overall) and risk of primary oesophageal (OAC) or gastric adenocarcinoma (GAC). METHODS: From nine European countries, 420,449 participants were recruited between 1991 and 2000 and followed-up for a mean of 8.8 years to register incident GAC and OAC. Information on physical activity (PA), diet, lifestyle and health-related variables was obtained at baseline. Helicobacter pylori infection status was considered in a subset of 1,211 participants. Analyses were repeated by tumour site (cardia/non-cardia) and histological type (intestinal/diffuse). RESULTS: During the follow-up, 410 GAC and 80 OAC occurred. A lower risk of overall and non-cardia GAC was found for increasing levels of a PA index which combined occupational PA with weekly time spent in sports and cycling. The hazard ratio (HR) of GAC was 0.69, 95% CI: 0.50-0.94, for the comparison between active and inactive participants according to the PA index (HR = 0.44, 95% CI:0.26-0.74, for non-cardia GAC). No effect was found for cardia tumours or histological subtypes of GAC. PA of any kind was not associated with OAC. CONCLUSIONS: Overall and distal (non-cardia) gastric tumours were inversely associated with time spent on cycling and sports and a total PA index. No association was found for any type of PA and risk of cardia cancers of the stomach.
    • Serum levels of organochlorine pesticides in healthy adults from five regions of Spain.

      Jakszyn, Paula; Goni, Fernando; Etxeandia, Arsenio; Vives, Asuncion; Millan, Esmeralda; Lopez, Raul; Amiano, Pilar; Ardanaz, Eva; Barricarte, Aurelio; Chirlaque, M. Dolores; et al. (2009-09)
      The aim of this study was to measure of serum levels of p,p'-dichlorodiphenyl trichloroethane (p,p'-DDT), p,p'-dichlorodiphenyl dichlorethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB) in healthy adults in Spain. Furthermore, we also analyzed these levels according to dietary, other lifestyle factors and anthropometric characteristics. We measured the concentrations of such organochlorine pesticides (OCPs) in serum samples collected during 1992-1996 from 953 subjects aged 35-64 years, they were residents of five Spanish regions, they were randomly selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. OCPs were determined by means of gas chromatography with electron-capture detection (GC-ECD). The most frequent compound found in serum was p,p'-DDE, present in 98% of the samples, followed by HCB and beta-HCH, found in 89% and 77% of samples, respectively, while p,p'-DDT could be measured only in 26% of subjects. The geometric means of serum concentrations (ng/g lipid) were 822 for p,p'-DDE, 167 for beta-HCH, and 379 for HCB. The concentrations of all OCPs were positively associated with age and body mass index, and decreased along the period of blood collection. No association was found between OCPs levels and dietary factors. The concentrations of p,p'-DDE and beta-HCB were higher in Murcia, one of southern regions, most likely associated with intensive past use of pesticides related to agricultural practices, while higher levels of HCB were found in Navarra, located in the north, maybe due to industrial use rather than agricultural application.
    • Simultaneous genotyping of GSTT1 and GSTM1 null polymorphisms by melting curve analysis in presence of SYBR Green I.

      Marin, Fatima; Garcia, Nadia; Munoz, Xavier; Capella, Gabriel; Gonzalez, Carlos A.; Agudo, Antonio; Sala, Nuria (2010-05)
      Due to their ability to metabolize xenobiotics, glutathione S-transferases (GSTs) play an important role in cellular protection. GST family members mu (GSTM1) and theta (GSTT1) exhibit a common polymorphism that results in the complete deletion of the gene (null allele). Homozygous deletions, which result in the absence of the enzyme, are considered a risk factor for several diseases, including cancer. We report a simple, low cost, and high throughput assay for the simultaneous analysis of the GSTM1 and GSTT1 null polymorphisms in a single step. The assay is based on multiplex real-time PCR in the presence of SYBR Green I and genotype discrimination by melting curve analysis in a LightCycler. We have genotyped 792 samples to compare this new approach with conventional PCR followed by gel electrophoresis. Comparison of the methods gave a good agreement, with kappa values of 0.88 for GSTM1 and 0.64 for GSTT1. Reanalysis of discrepant samples indicated that absence of amplification of the larger GSTT1 fragment by conventional PCR accounted for most of the discrepancies. Moreover, the improved amplification efficiency of the real-time PCR results in a significant reduction of missing values. Due to its simplicity and low cost, this assay is well suited for the rapid analysis of GST-null genotypes in studies that involve large number of samples.
    • Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.

      Eussen, Simone J. P. M.; Vollset, Stein Emil; Hustad, Steinar; Midttun, Oivind; Meyer, Klaus; Fredriksen, Ase; Ueland, Per Magne; Jenab, Mazda; Slimani, Nadia; Ferrari, Pietro; et al. (2010-01)
      B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.