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A recent study examined associations of tagging single nucleotide polymorphisms (tagSNPs) in 43 fatty acid metabolism-related genes and risk of colorectal cancer (CRC), showing rs8752, rs2612656 and a haplotype [comprising both of the single nucleotide polymorphisms (SNPs)] in the hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) gene to be positively associated with CRC risk. In the present study, we attempted to replicate these single marker and haplotype associations, using 1795 CRC cases and 1805 controls from the German Darmkrebs: Chancen der Verhütung durch Screening study (DACHS). In addition to rs8752 and rs2612656, HPGD tagSNPs rs9312555, rs17360144 and rs7349744 were genotyped for haplotype analyses. Except for a marginally significant inverse association of HPGD rs8752 with CRC risk [odds ratio (OR) = 0.85; 95% confidence interval (CI) = 0.74, 0.98; P = 0.03], none of the analyzed tagSNPs showed any association with CRC. Subset analyses for colon and rectal cancers yielded similar, yet non-significant risk estimates at all five loci. Also, none of the haplotypes was found to be associated with CRC, colon or rectal cancers. However, rs8752 was significantly associated with a decreased risk of CRC among individuals with a body mass index < 30 (OR = 0.82, 95% CI = 0.70, 0.95, P = 0.01) as well as among smokers (OR = 0.74, 95% CI = 0.61, 0.90, P = 0.003). Yet, our data do not support the previously reported associations of HPGD tagSNPs and risk of CRC.

Contains fulltext : 51396.pdf (Publisher’s version ) (Closed access) Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with

Both genetic variants and messenger RNA (mRNA) expression of DNA repair and tumor suppressor genes have been investigated as molecular markers for therapy outcome. However, the phenotypic impact of genetic variants often remained unclear, thus the rationale of their use in risk prediction may be limited. We therefore analyzed genetic variants together with anthropometric and lifestyle factors to see how these affect mRNA levels of ERCC1 , MDM2 and TP53 in primary blood lymphocytes. mRNA expression was measured in 376 prostate cancer patients by quantitative real-time polymerase chain reaction after reverse transcription, and ERCC1 rs11615 T>C, ERCC1 rs3212986 C>A, MDM2 rs2279744 T>G and TP53 rs17878362 (p53PIN3) polymorphisms were determined. Considerable interindividual differences in mRNA expression were found (coefficients of variation: ERCC1 , 45%; MDM2 , 43% and TP53 , 35%). ERCC1 expression was positively correlated with plasma levels of β-carotene ( P = 0.03) and negatively correlated with canthaxanthin ( P = 0.02) and lutein ( P = 0.02). Overall, the polymorphisms affected mRNA expression only weakly. Carriers of a distinct ERCC1 haplotype (CC) showed, however, significantly lower expression values than non-carriers ( P = 0.001). Applying logistic regression, we found that CC haplotype carriers had a 1.69-fold increased odds ratio (95% confidence interval: 1.06–2.71) for reduced ERCC1 mRNA levels. This low ERCC1 expression might be associated with reduced DNA repair and better therapy response. In summary, the association we have found between ERCC1 genotype and mRNA expression supports recent clinical observations that genetic variation in ERCC1 can affect treatment outcome and prognosis. Our study further revealed a modulating effect by nutritional factors.

Cancer epidemiologyCancer type:Gastric cancerStudy design:EPIC cohort study and nested case-control studyStudy size:521 457 subjects (368 010 women and 153 447 men) for the cohort and 314 adenocarcinoma cases for the case-control studyDescription of cohort(s) studied:subjets collected from 10 European countries, aged 35-70 years, and recruited mostly between 1992 and 1998Exposure(s) evaluated:dietary intake of nitrosodimethylamine (NDMA) and meat and faecal ATNC formationConfounders controlled for:plasma vitamin C and H.pylori infectionImpact on risk: NDMA dietary intake HR, 1.00; 95% CI, 0.70-1.43 for an increment of 1 mg of NDMA. ENOC (HR, 1.18; 95% CI, 0.99-1.39 for an increment of 40 mg of EN). ENOC and vit. C intake (OR, 3.24; 95% CI, 1.77-5.93 for those with less than 40 micromol/l of plasma vitamin C)Notes:non-cardia GC was positively associated with ENOC exposure but not with dietary NDMADietary modulation of cancer & cancer biomarkers Dietary item or component studied:NDMAOutcome studied (cancer or cancer biomarker):gastric cancerStudy type (in vitro, animals, humans): humansStudy design (if human):prospective, nested case-controlStudy size (if human):521 457 subjects (368 010 women and 153 447 men) for the cohort and 314 adenocarcinoma cases for the case-control studyTissue/biological material/sample size:plasma for the nested study, faeces for the cohortMode of exposure (if in vivo):red meat consumption. Keywords classification: adverse effects;Adenocarcinoma;Animals;Antibodies;Ascorbic Acid;blood;cancer epidemiology;Case-Control Studies;Cattle;Diet;dietary modulation of cancer & cancer biomarkers;Dimethylnitrosamine;epidemiology;etiology;Europe;Female;Helicobacter Infections;Helicobacter pylori;Humans;Iron;lifestyle modulation of cancer & cancer biomarkers;metabolism;Male;Meat;Middle Aged;Nitrosamines;pharmacology;Prospective Studies;Research;Risk Factors;Spain;Stomach Neoplasms;analysis; The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident cases of GC that had occurred after 6.6 average years of follow-up. An index of endogenous NOC (ENOC) formation was estimated using data of the iron content from meat intake and faecal apparent total NOC formation according to previous published studies. Antibodies to Helicobacter pylori and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. Exposure to NDMA was < 1 microg on average compared with 93 mug on average from ENOC. There was no association between NDMA intake and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40 microg/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although the number of not infected cases is low, our data suggest a possible interaction between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC formation may account for our previously reported association between red and processed meat consumption and gastric cancer risk.