Dataset Information

Toll-like receptor genes and their association with colon and rectal cancer development and prognosis.

ABSTRACT: Toll-like receptors (TLRs) are mediators of inflammation in the gut and potentially important modulators of colon and rectal cancer risk. We use data from a population-based study of incident colon cancer cases (n = 1,555) and controls (n = 1,956) and rectal cancer cases (n = 754) and controls (n = 959). We evaluate genetic variation in TLR2 (six SNPs), TLR3 (four SNPs) and TLR4 (eight SNPs) with risk of developing colon or rectal cancer and survival after diagnosis. TLR3 rs11721827 was associated with rectal cancer (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.02, 1.58 for AC/CC vs. AA genotype, Wald p = 0.035; adjusted p = 0.126); TLR3 rs3775292 and TLR4 rs11536898 were associated with colon cancer (OR 0.68, 95% CI 0.49, 0.95 for GG vs. CC/CG and OR 0.50. 95% CI 0.29, 0.87 for AA vs. CA/CC, respectively; Wald p = 0.023 and 0.015; adjusted p = 0.085 and 0.101, respectively). TLR2 rs7656411 and rs3804099, respectively, interacted with nonsteroidal anti-inflammatory drug (NSAID) use and cigarette smoking to alter risk of colon cancer (adjusted p = 0.034 and 0.077); TLR3 rs11721827 interacted with NSAID use to alter risk of colon cancer (adjusted p = 0.071). TLR3 rs3775292 interacted with dietary carbohydrates to alter colon cancer risk and with dietary carbohydrates and saturated fat to alter rectal cancer risk (adjusted p = 0.064, 0.0035 and 0.025, respectively). Multiple SNPs in TLR2 and TLR4 were associated with colon cancer survival. Although few independent associations with TLR genes were observed, we observed significant interaction of TLR2 and TLR3 with hypothesized lifestyle factors. Interaction with dietary factors remained significant for rectal cancer after adjustment for multiple comparisons.

SUBMITTER: Slattery ML

PROVIDER: S-EPMC3290725 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Toll-like receptor genes and their association with colon and rectal cancer development and prognosis.

Slattery Martha L ML Herrick Jennifer S JS Bondurant Kristina L KL Wolff Roger K RK

International journal of cancer 20111020 12

Toll-like receptors (TLRs) are mediators of inflammation in the gut and potentially important modulators of colon and rectal cancer risk. We use data from a population-based study of incident colon cancer cases (n = 1,555) and controls (n = 1,956) and rectal cancer cases (n = 754) and controls (n = 959). We evaluate genetic variation in TLR2 (six SNPs), TLR3 (four SNPs) and TLR4 (eight SNPs) with risk of developing colon or rectal cancer and survival after diagnosis. TLR3 rs11721827 was associat ...[more]

PMID: 21792899

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Project description:BackgroundAssociations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process.MethodsWe used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls) and rectal (n = 754 cases, 959 controls) cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH), SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk.ResultsAfter adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208). Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300). Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR) and rectal cancer (SepX1 increased HRR).ConclusionsFindings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is modified by lifestyle.

Dataset Information

Toll-like receptor genes and their association with colon and rectal cancer development and prognosis.

Publications

Toll-like receptor genes and their association with colon and rectal cancer development and prognosis.

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