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Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality
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2012 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 72, no 2, p. 209-216Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Common genetic variants in the Toll-like receptor 4 (TLR4), which is involved in inflammation and immune response pathways, may be important for prostate cancer.

METHODS: In a large nested case-control study of prostate cancer in the Physicians' Health Study (1982-2004), 10 single nucleotide polymorphisms (SNPs) were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kb up and downstream. Unconditional logistic regression was used to assess associations of these SNPs with total prostate cancer incidence, and with prostate cancers defined as advanced stage/lethal (T3/T4, M1/N1(T1-T4), lethal) or high Gleason grade (7 (4 + 3) or greater). Cox-proportional hazards regression was used to assess progression to metastases and death among prostate cancer cases.

RESULTS: The study included 1,267 controls and 1,286 incident prostate cancer cases, including 248 advanced stage/lethal and 306 high grade cases. During a median follow-up of 10.6 years, 183 men died of prostate cancer or developed distant metastases. No statistically significant associations between the TLR4 SNPs were found for total prostate cancer incidence, including SNPs for which an association was reported in other published studies. Additionally, there were no significant associations with TLR4 SNPS and the incidence of advanced stage/lethal, or high grade cancers; nor was there evidence among prostate cancer cases for associations of TLR4 SNPs with progression to prostate cancer specific mortality or bony metastases.

CONCLUSIONS: Results from this prospective nested case-control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012. Vol. 72, no 2, p. 209-216
Keywords [en]
TLR4; prostate cancer; inflammation; molecular epidemiology
National Category
Endocrinology and Diabetes Urology and Nephrology
Identifiers
URN: urn:nbn:se:oru:diva-27789DOI: 10.1002/pros.21423ISI: 000298479200011PubMedID: 21563195Scopus ID: 2-s2.0-84455192192OAI: oai:DiVA.org:oru-27789DiVA, id: diva2:608755
Note

Funding Agency:

National Institutes of Health CA090598-03  5 T32 CA09001-35  HL-26490  HL-34595  CA-097193  CA-34944  CA-141298  CA-40360

Available from: 2013-03-01 Created: 2013-03-01 Last updated: 2017-12-06Bibliographically approved

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Fall, Katja

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