{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:04:34Z","timestamp":1777446274038,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,9,11]],"date-time":"2013-09-11T00:00:00Z","timestamp":1378857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>Populations in north central China are at high risk for gastric cancers (GC), and altered FAS\u2010mediated cell signaling and\/or apoptosis may contribute to this risk. We examined the association of 554 single nucleotide polymorphisms (SNPs) in 53 Fas signaling\u2010related genes using a pathway\u2010based approach in 1758 GC cases (1126 gastric cardia adenocarcinomas (GCA) and 632 gastric noncardia adenocarcinomas (GNCA)), and 2111 controls from a genome\u2010wide association study (GWAS) of GC in ethnic Chinese. SNP associations with risk of overall GC, GCA and GNCA were evaluated using unconditional logistic regressions controlling for age, sex and study. Gene\u2010 and pathway\u2010based associations were tested using the adaptive rank\u2010truncated product (ARTP) method. Statistical significance was evaluated empirically by permutation. Significant pathway\u2010based associations were observed for Fas signaling with risk of overall GC (p = 5.5E\u201004) and GCA (<jats:italic>p<\/jats:italic> = 6.3E\u201003), but not GNCA (<jats:italic>p<\/jats:italic>= 8.1E\u201002). Among examined genes in the Fas signaling pathway, <jats:italic>MAP2K4, FAF1, MAPK8, CASP10, CASP8, CFLAR, MAP2K1, CAP8AP2, PAK2<\/jats:italic> and <jats:italic>IKBKB<\/jats:italic> were associated with risk of GC (nominal <jats:italic>p<\/jats:italic> &lt; 0.05), and <jats:italic>FAF1<\/jats:italic> and <jats:italic>MAPK8<\/jats:italic> were significantly associated with risk of both GCA and GNCA (nominal <jats:italic>p<\/jats:italic>&lt; 0.05). Our examination of genetic variation in the Fas signaling pathway is consistent with an association of altered Fas signaling and\/or apoptosis with risk of GC. As one of the first attempts to investigate a pathway\u2010level association, our results suggest that these genes and the Fas signaling pathway warrant further evaluation in relation to GC risk in other populations.<\/jats:p>","DOI":"10.1002\/ijc.28415","type":"journal-article","created":{"date-parts":[[2013,8,7]],"date-time":"2013-08-07T10:28:56Z","timestamp":1375871336000},"page":"822-831","source":"Crossref","is-referenced-by-count":21,"title":["Genetic variants in fas signaling pathway genes and risk of gastric cancer"],"prefix":"10.1002","volume":"134","author":[{"given":"Paula L.","family":"Hyland","sequence":"first","affiliation":[{"name":"Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics National Cancer Institute (NCI), National Institutes of Health (NIH) Bethesda MD, USA"},{"name":"Cancer Prevention Fellowship Program, Division of Cancer Prevention NCI, NIH Bethesda MD, 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