Browsing by Author "Murff, Harvey J."

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    A study of prostaglandin pathway genes and interactions with current non-steroidal anti-inflammatory drug use in colorectal adenoma
    (American Association for Cancer Research, 2012) Edwards, Todd L.; Shrubsole, Martha J.; Cai, Qiuyin; Li, Guoliang; Dai, Qi; Rex, Douglas; Ulbright, Thomas M.; Fu, Zhenming; Murff, Harvey J.; Smalley, Walter; Ness, Reid; Zheng, Wei; Medicine, School of Medicine
    Colorectal cancer (CRC) is the second leading cause of cancer-related death and usually arises from colorectal polyps. Screening and removal of polyps reduce mortality from CRC. Colorectal polyps are known to aggregate in families; however the genetic determinants for risk of polyps are unknown. In addition, it has been shown that nonsteroidal anti-inflammatory drug (NSAID) use decreases the risk of CRC and the incidence and size of polyps. In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to evaluate selected genes from the prostaglandin (PG) metabolism and signaling pathways for association with risk of polyps and for interactions with NSAIDs. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian polyp cases and 3,285 Caucasian controls. We carried out multivariable logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. We detected association signals in the genes PGE receptor 3 (PTGER3) and 15-hydroxyprostaglandin dehydrogenase (HPGD), both strong biologic candidates for influence on polyp risk. We did not observe the previously reported effects and effect modification in PG-endoperoxide synthase 2 (PTGS2), PGE receptor 2 (PTGER2), or PGE receptor 4 (PTGER4), although we did observe a single nucleotide polymorphism in PTGER2 associated with risk of multiple adenomas. We also observed effect modification of the HPGD signal by NSAID exposure.
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    Genome-wide association study identifies possible genetic risk factors for colorectal adenomas
    (American Association for Cancer Research, 2013) Edwards, Todd L.; Shrubsole, Martha J.; Cai, Qiuyin; Li, Guoliang; Dai, Qi; Rex, Douglas K.; Ulbright, Thomas M.; Fu, Zhenming; Delahanty, Ryan H.; Murff, Harvey J.; Smalley, Walter; Ness, Reid M.; Zheng, Wei; Pathology and Laboratory Medicine, School of Medicine
    Background: Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown. Methods: In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls. We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. Results: No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10(-4)), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10(-6)). Conclusions: This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies. Impact: These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.