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Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

ABSTRACT: BACKGROUND:Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted. METHODS:We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided. RESULTS:We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003). CONCLUSIONS:Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer.

SUBMITTER: Hung RJ

PROVIDER: S-EPMC4675100 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

Hung Rayjean J RJ Ulrich Cornelia M CM Goode Ellen L EL Brhane Yonathan Y Muir Kenneth K Chan Andrew T AT Marchand Loic Le LL Schildkraut Joellen J Witte John S JS Eeles Rosalind R Boffetta Paolo P Spitz Margaret R MR Poirier Julia G JG Rider David N DN Fridley Brooke L BL Chen Zhihua Z Haiman Christopher C Schumacher Fredrick F Easton Douglas F DF Landi Maria Teresa MT Brennan Paul P Houlston Richard R Christiani David C DC Field John K JK Bickeböller Heike H Risch Angela A Kote-Jarai Zsofia Z Wiklund Fredrik F Grönberg Henrik H Chanock Stephen S Berndt Sonja I SI Kraft Peter P Lindström Sara S Al Olama Ali Amin AA Song Honglin H Phelan Catherine C Wentzensen Nicholas N Peters Ulrike U Slattery Martha L ML Sellers Thomas A TA Casey Graham G Gruber Stephen B SB Hunter David J DJ Amos Christopher I CI Henderson Brian B

Journal of the National Cancer Institute 20150829 11

<h4>Background</h4>Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted.<h4>Methods</h4>We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. ...[more]

PMID: 26319099

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Project description:BackgroundPatient medical out-of-pocket expenses are thought to be rising worldwide yet data describing trends over time is scant. We evaluated trends of out-of-pocket expenses for patients in Australia with one of five major cancers in the first-year after diagnosis.MethodsParticipants from the QSKIN Sun and Health prospective cohort Study with a histologically confirmed breast, colorectal, lung, melanoma, or prostate cancer diagnosed between 2011 and 2015 were included (n = 1965). Medicare claims data on out-of-pocket expenses were analysed using a two-part model adjusted for year of diagnosis, health insurance status, age and education level. Fisher price and quantity indexes were also calculated to assess prices and volumes separately.ResultsOn average, patients with cancer diagnosed in 2015 spent 70% more out-of-pocket on direct medical expenses than those diagnosed in 2011. Out-of-pocket expenses increased significantly for patients with breast cancer (mean AU$2513 in 2011 to AU$6802 in 2015). Out-of-pocket expenses were higher overall for individuals with private health insurance. For prostate cancer, expenses increased for those without private health insurance over time (mean AU$1586 in 2011 to AU$4748 in 2014) and remained stable for those with private health insurance (AU$4397 in 2011 to AU$5623 in 2015). There were progressive increases in prices and quantities of medical services for patients with melanoma, breast and lung cancer. For all cancers, prices increased for medicines and doctor attendances but fluctuated for other medical services.ConclusionOut-of-pocket expenses for patients with cancer have increased substantially over time. Such increases were more pronounced for women with breast cancer and those without private health insurance. Increased out-of-pocket expenses arose from both higher prices and higher volumes of health services but differ by cancer type. Further efforts to monitor patient out-of-pocket costs and prevent health inequities are required.

Dataset Information

Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

Publications

Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

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