JAK/STAT/SOCS‐signaling pathway and colon and rectal cancer1. Issue 2 (28th November 2011)

• Record Type: Journal Article
• Authors: Slattery, Martha L.; Lundgreen, Abbie; Kadlubar, Susan A.; Bondurant, Kristina L.; Wolff, Roger K.
• Is Part Of: Molecular carcinogenesis. Volume 52:Issue 2(2013:Feb.)
• Page Start: 155
• Page End: 166
• Publication Date: 2011-11-28
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.21841
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in immune function and cell growth. We evaluated the association between genetic variation in <italic>JAK1</italic> (10 SNPs), <italic>JAK2</italic> (9 SNPs), <italic>TYK2</italic> (5 SNPs), suppressors of cytokine signaling (<italic>SOCS</italic>)<italic>1</italic> (2 SNPs), <italic>SOCS2</italic> (2 SNPs), <italic>STAT1</italic> (16 SNPs), <italic>STAT2</italic> (2 SNPs), <italic>STAT3</italic> (6 SNPs), <italic>STAT4</italic> (21 SNPs), <italic>STAT5A</italic> (2 SNPs), <italic>STAT5B</italic> (3 SNPs), <italic>STAT6</italic> (4 SNPs) with risk of colorectal cancer. We used data from population‐based case‐control studies (colon cancer <italic>n</italic> = 1555 cases, 1, 956 controls; rectal cancer <italic>n</italic> = 754 cases, 959 controls). <italic>JAK2</italic>, <italic>SOCS2</italic>, <italic>STAT1</italic>, <italic>STAT3</italic>, <italic>STAT5A</italic>, <italic>STAT5B</italic>, and <italic>STAT6</italic> were associated with colon cancer; <italic>STAT3</italic>, <italic>STAT4</italic>, <italic>STAT6</italic>, and <italic>TYK2</italic> were associated with rectal cancer. Given the biological role of the JAK/STAT‐signaling pathway and cytokines, we evaluated interaction with <italic>IFNG, TNF, </italic> and <italic>IL6;</italic> numerous statistically significant associations after adjustment for multiple comparisons were observed. The following statistically significant interactions were observed: <italic>TYK2</italic> with aspirin/NSAID use; <italic>STAT1</italic>, <italic>STAT4</italic>, and <italic>TYK2</italic> with estrogen status; and <italic>JAK2</italic>, <italic>STAT2</italic>, <italic>STAT4</italic>, <italic>STAT5A</italic>, <italic>STAT5B</italic>, and <italic>STAT6</italic> with smoking status and colon cancer risk; <italic>JAK2</italic>, <italic>STAT6</italic>, and <italic>TYK2</italic> with aspirin/NSAID use; <italic>JAK1</italic> with estrogen status; <italic>STAT2</italic> with cigarette smoking and rectal cancer. <italic>JAK2</italic>, <italic>SOCS1</italic>, <italic>STAT3</italic>, <italic>STAT5</italic>, and <italic>TYK2</italic> were associated with colon cancer survival (hazard rate ratio (HRR) of 3.3 95% CI 2.01, 5.42 for high mutational load). <italic>JAK2</italic>, <italic>SOCS1</italic>, <italic>STAT1</italic>, <italic>STAT4</italic>, and <italic>TYK2</italic> were associated with rectal cancer survival (HRR 2.80 95% CI 1.63, 4.80). These data support the importance of the JAK/STAT‐signaling pathway in colorectal cancer and suggest targets for intervention. © 2011 Wiley Periodicals, Inc.</p> </abstract>