Dataset Information

Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study.

ABSTRACT:

Background

Folate-associated one-carbon metabolism (FOCM) is an important pathway in colorectal neoplasia risk but data on genetic variation in this pathway are largely limited to studies of single SNPs in selected genes.

Methods

We used a comprehensive tagSNP approach to study the association between genetic variation in 11 genes in the FOCM pathway and risk of incident distal colorectal adenomas in a sigmoidoscopy-based case-control study. We included 655 cases (one or more adenomas) and 695 controls (no adenomas) recruited from one of two Kaiser Permanente clinics between 1991 and 1995. We assessed a total of 159 tagSNPs selected using Haploview Tagger as well as selected non-synonymous SNPs. We used unconditional logistic regression to model the association between SNPs and risk of distal adenomas, assuming a log-additive model.

Results

Five SNPs in the SLC19A1 (RFC1) gene: rs1051266 (G80A), rs283895, rs2236484, rs12482346, and rs2838958 were associated with adenoma risk after correction for multiple testing (all corrected p values ≤ 0.043). The non-synonymous SLC19A1 SNP G80A interacted significantly with the MTHFR C677T genotype (interaction p value = 0.018).

Conclusion

Our data suggest that genetic variation in SLC19A1 may modify the risk of distal colorectal adenoma.

SUBMITTER: Levine AJ

PROVIDER: S-EPMC3059778 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Publications

Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study.

Levine A Joan AJ Lee Won W Figueiredo Jane C JC Conti David V DV Vandenberg David J DJ Davis Brian D BD Edlund Christopher K CK Henning Susanne M SM Heber David D Stern Mariana C MC Haile Robert W RW

Cancer causes & control : CCC 20110128 4

<h4>Background</h4>Folate-associated one-carbon metabolism (FOCM) is an important pathway in colorectal neoplasia risk but data on genetic variation in this pathway are largely limited to studies of single SNPs in selected genes.<h4>Methods</h4>We used a comprehensive tagSNP approach to study the association between genetic variation in 11 genes in the FOCM pathway and risk of incident distal colorectal adenomas in a sigmoidoscopy-based case-control study. We included 655 cases (one or more aden ...[more]

PMID: 21274745

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Project description:Preeclampsia is a hypertensive, multi-system pregnancy disorder whose pathophysiology remains unclear. Elevations in circulating soluble endoglin (sENG) and placental/blood ENG mRNA expression antedate the clinical onset of preeclampsia. This study investigated if endoglin (ENG) pathway genetic variation was also associated with the development of preeclampsia.We used a case-control candidate gene association design. Data from 355 white (181 preeclampsia cases/174 controls) and 60 black (30 preeclampsia cases/30 controls) women matched on ancestry, age, and parity were analyzed. Tagging single nucleotide polymorphisms (tSNPs) and potentially functional SNPs in ENG, TGF?1, TGF?R1, ALK1, and TGF?R2 were genotyped with iPLEX® and TaqMan®. Chi-square or Fisher's exact tests were used to conduct allele/genotype/haplotype tests in white/black subgroups separately. Odds ratios were computed with binary logistic regression for tSNPs with significant genotype tests.Of the 49 SNPs evaluated, variation in two ENG tSNPs (rs11792480, rs10121110) and one TGF?R2 tSNP (rs6550005) was associated with preeclampsia in white women (P <0.05, each). In black women, variation in two TGF?1 tSNPs (rs4803455, rs4803457), one TGF?R1 tSNP (rs10739778), and three TGF?R2 tSNPs (rs6550005, rs1346907, rs877572) was associated with preeclampsia (P <0.05, each). Further evaluation of ENG tSNP rs10121110 revealed that white women inheriting the AA genotype were 2.29 times more likely to develop preeclampsia compared to the GG genotype (P?=?0.008, [99% CI: 1.02 to 5.13]). For black women, similar evaluation of TGF?1 tSNP rs4803457 revealed women inheriting the CT genotype were 7.44 times more likely to develop preeclampsia than those with the CC genotype (P?=?0.005, [99% CI: 1.19 to 46.41]).ENG pathway genetic variation is associated with preeclampsia. Different ENG pathway genes may be involved in preeclampsia development among white and black women. Additional studies are needed to validate these findings and to determine if genetic variation in ENG pathway genes impacts ENG and sENG levels in preeclampsia.

Dataset Information

Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study.

Background

Methods

Results

Conclusion

Publications

Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study.

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