Genetic variation in TLR or NFkappaB pathways and the risk of breast cancer: a case-control studyReportar como inadecuado




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BMC Cancer

, 13:219

Genetics, genomics and epigenetics

Abstract

BackgroundToll-like receptors TLRs and the transcription factor nuclear factor-κB NFκB are important in inflammation and cancer.

MethodsWe examined the association between breast cancer risk and 233 tagging single nucleotide polymorphisms within 31 candidate genes involved in TLR or NFκB pathways. This population-based study in the Seattle area included 845 invasive breast cancer cases, diagnosed between 1997 and 1999, and 807 controls aged 65–79.

ResultsVariant alleles in four genes were associated with breast cancer risk based on gene-level tests: MAP3K1, MMP9, TANK, and TLR9. These results were similar when the risk of breast cancer was examined within ductal and luminal subtypes. Subsequent exploratory pathway analyses using the GRASS algorithm found no associations for genes in TLR or NFκB pathways. Using publicly available CGEMS GWAS data to validate significant findings N = 1,145 cases, N = 1,142 controls, rs889312 near MAP3K1 was confirmed to be associated with breast cancer risk P = 0.04, OR 1.15, 95% CI 1.01–1.30. Further, two SNPs in TANK that were significant in our data, rs17705608 P = 0.05 and rs7309 P = 0.04, had similar risk estimates in the CGEMS data rs17705608 OR 0.83, 95% CI 0.72–0.96; CGEMS OR 0.90, 95% CI 0.80–1.01 and rs7309 OR 0.83, 95% CI 0.73–0.95; CGEMS OR 0.91, 95% CI 0.81–1.02.

ConclusionsOur findings suggest plausible associations between breast cancer risk and genes in TLR or NFκB pathways. Given the few suggestive associations in our data and the compelling biologic rationale for an association between genetic variation in these pathways and breast cancer risk, further studies are warranted that examine these effects.

KeywordsBreast cancer Genetic variation Inflammation TLR NFκB Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-13-219 contains supplementary material, which is available to authorized users.

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