Abstract:
:The effects of polymorphisms in genes coding for key folate metabolism enzymes such as thymidylate synthetase (TS) on colorectal neoplasia risk are likely to be influenced by gene-gene and gene-nutrient interactions. We investigated the combined effects of three polymorphisms in the TS gene region, TSER, TS 3R G>C, and TS 1494del6, dietary intakes of folate and other B vitamins, and genotype for other folate metabolism variants, in a colorectal adenoma (CRA) case-control study. Individuals homozygous for TS 1494del6 del/del were at significantly reduced CRA risk compared to those with either ins/del or ins/ins genotypes (odds ratio 0.52; 95% confidence interval: 0.31-0.85, P=0.009). We also observed evidence of interactions between TS 1494del6 genotype and intake of folate, and vitamins B6 and B12, and MTHFR C677T genotype, with the reduction in risk in del/del homozygotes being largely confined to individuals with high nutrient intakes and MTHFR 677CC genotype (P interaction=0.01, 0.006, 0.03, and 0.07, respectively). TSER genotype, when considered either alone or in combination with TS 3R G>C genotype, did not significantly influence CRA risk. These findings support a role for TS in colorectal carcinogenesis, and provide further evidence that functional polymorphisms in folate metabolism genes act as low-risk alleles for colorectal neoplasia and participate in complex gene-gene and gene-nutrient interactions.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Hubner RA,Liu JF,Sellick GS,Logan RF,Houlston RS,Muir KRdoi
10.1038/sj.bjc.6604056subject
Has Abstractpub_date
2007-11-19 00:00:00pages
1449-56issue
10eissn
0007-0920issn
1532-1827pii
6604056journal_volume
97pub_type
杂志文章abstract::In haemagglutination tests we have found that the monoclonal antibody B5 discriminates between erythrocytes from patients with malignant cancer (total 386; greater than 80% B5 positive) and individuals with no known tumour (total 247; less than 20% B5 positive). The B5 antigen detected on intact erythrocytes is a tigh...
journal_title:British journal of cancer
pub_type: 杂志文章
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journal_title:British journal of cancer
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
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doi:
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pub_type: 杂志文章
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pub_type: 临床试验,杂志文章
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journal_title:British journal of cancer
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doi:10.1038/bjc.1996.29
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更新日期:1997-01-01 00:00:00
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doi:10.1038/sj.bjc.6604195
更新日期:2008-02-12 00:00:00
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