Chronic inflammation has been implicated in colorectal carcinogenesis. Several studies have investigated the relationship between C-reactive protein (CRP), a biomarker of inflammation, and colorectal cancer and adenomas, resulting in inconsistent findings. The present study examined the relationship between circulating levels of high-sensitivity CRP and colorectal adenomas. The study subjects comprised 646 cases of colorectal adenoma and 635 controls of normal total colonoscopy among men receiving a preretirement health examination at two hospitals of the Self Defense Forces. Statistical adjustment was made for cigarette smoking, alcohol use, body mass index, physical activity, and other potential confounders. The multivariate-adjusted geometric means showed no measurable differences between adenoma cases and controls, but were higher among cases with larger adenomas (trend P = 0.03). Likewise, although the prevalence odds of colorectal adenomas did not differ according to CRP levels as categorized at the 30th, 60th, and 90th percentiles in the controls, higher levels of CRP were associated with a statistically significant increase in the prevalence odds of large adenomas (³5 mm), but not of small adenomas (<5 mm). The multivariate-adjusted odds ratios of large adenomas for the lowest to highest categories of CRP were 1.00 (referent), 1.81 (95% confidence interval 1.17-2.80), 1.61 (95% confidence interval 1.03-2.52), and 2.21 (95% confidence interval 1.28-3.84), respectively (trend P = 0.01). A positive association between CRP and prevalence odds of large adenomas was not modified by either smoking or overweight. These findings suggest that inflammation is linked to the growth of colorectal adenomas. (Cancer Sci 2009; 100: 709-714) C hronic inflammation has been implicated in carcinogenesis. (1,2) Inflammatory cytokines are considered to promote carcinogenesis by inducing oxidative DNA damage, stimulating cell proliferation and angiogenesis, and inhibiting apoptosis.(1,2) Particular interest has been drawn to the role of inflammation in colorectal carcinogenesis. Chronic inflammatory bowel diseases are known to confer increased risk of colorectal cancer, (3,4) and use of aspirin or non-steroidal anti-inflammatory drugs has consistently been related to reduced risk of colorectal adenomas and cancer in observational and intervention studies.(5-8) Recently, several prospective studies have investigated the relationship between C-reactive protein (CRP), a biomarker of inflammation, and colorectal cancer risk, resulting in inconsistent findings. (9)(10)(11)(12)(13)(14)(15)(16) An increased risk of colorectal cancer associated with increased concentrations of CRP was first reported in the CLUE II study. (9) A positive association between CRP and colorectal caner risk was replicated in three subsequent studies, (10)(11)(12) but no such association was observed in four other studies. (13)(14)(15)(16) One of the latter studies even suggested a decreased risk associated with high concentrations of CRP. (13) Results are al...

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Folate-mediated one-carbon metabolism has been implicated in colorectal carcinogenesis. We investigated associations of functional genetic polymorphisms of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS) with colorectal adenomas. The study subjects were 455 cases of colorectal adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp deletion polymorphism at position 1494 in the 3' untranslated region (TS 1494del6). We also examined the alcohol-genotype and gene-gene interactions on adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99 (95% confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The increase in the risk associated with MTR 2756GG genotype was evident in men with high alcohol consumption (≥30 mL/d), but not in those with low alcohol consumption (interaction P = 0.03). Men who were homozygous for the TSER double-repeat allele had a slightly decreased risk of colorectal adenomas as compared with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS 1494del6 was associated with colorectal adenomas. There was no measurable interaction either between MTR A2756G and MTRR A66G or between TSER and TS 1494del6. MTR A2756G appears to be associated with colorectal adenoma risk differently according to alcohol consumption. The MTR-catalyzed reaction may play an important role in the development of colorectal adenomas.

Combination of the CYP1A1 2C and NQO1 609CC genotypes was associated with a decreased risk of colorectal adenomas regardless of smoking status.

Coffee drinking is protective against glucose intolerance. A possible effect modification of GGT on the coffee-DM association warrants further studies.

Objective: Coffee consumption has been related to decreased risk of type 2 diabetes, but it is unclear whether this relation is affected by cytochrome P450 1A2 (CYP1A2), a primary enzyme of caffeine metabolism. We examined the associations of two functional genetic polymorphisms of CYP1A2 with glucose tolerance status and the effect modification of the CYP1A2 polymorphisms on the association between coffee and impaired glucose metabolism. Methods:The subjects were 2263 male officials aged 46-59 years in the Self-Defense Forces in Japan. Individual glucose tolerance status was classified into normal glucose tolerance, Impaired Fasting Glycemia (IFG), Impaired Glucose Tolerance (IGT) or type 2 diabetes by a 75 g oral glucose tolerance test. IFG and IGT were combined as a single entity (IFG/IGT). Coffee consumption was assessed by a self-administered questionnaire. The CYP1A2 polymorphisms (CYP1A2*1C and CYP1A2*1F) were genotyped by the PCR-RFLP method.Results: Neither CYP1A2*1C nor CYP1A2*1F showed a measurable association with IFG/IGT or type 2 diabetes. Coffee consumption was inversely associated with IFG/IGT and type 2 diabetes. The inverse association between coffee and type 2 diabetes was significant in the GG genotype of CYP1A2*1C, but not in the GA and AA genotypes combined (interaction P=0.07). This effect modification was more evident among smokers (interaction P=0.03). Neither of the two polymorphisms modified the association between coffee and IFG/IGT. Conclusions:The CYP1A2*1C polymorphism modified the association between coffee and type 2 diabetes, especially among current smokers, suggesting that caffeine may not be negligible in the coffee-diabetes association.