Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection-Related Cancers--Hepatocellular Carcinoma and Cervical Cancer

Jian Yin; Juan Wen; Dong Hang; Jing Han; Jie Jiang; Ci Song; Yao Liu; Jibin Liu; Li Liu; Liguo Zhu; Jianguo Chen; Xiangjun Zhai; Shuanghua Xie; Zhibin Hu; Hongbing Shen; Min Dai; Ni Li

doi:10.1371/journal.pone.0132352

Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection-Related Cancers--Hepatocellular Carcinoma and Cervical Cancer

PLoS One. 2015 Jul 6;10(7):e0132352. doi: 10.1371/journal.pone.0132352. eCollection 2015.

Authors

Jian Yin¹, Juan Wen¹, Dong Hang¹, Jing Han¹, Jie Jiang¹, Ci Song¹, Yao Liu², Jibin Liu³, Li Liu⁴, Liguo Zhu⁵, Jianguo Chen⁶, Xiangjun Zhai⁵, Shuanghua Xie⁷, Zhibin Hu¹, Hongbing Shen¹, Min Dai⁷, Ni Li⁷

Affiliations

¹ Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
² Pathology Center and Department of Pathology, Soochow University, Suzhou, China.
³ Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China.
⁴ Digestive Endoscopy Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁵ Department of Infection Diseases, Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
⁶ Qidong Liver Cancer Institute, Qidong, China.
⁷ National Office for Cancer Prevention and Control, Cancer Institute and Hospital, Chinese Academy of Medical Science, Beijing, China.

Abstract

Caspase recruitment domain family, member 8 (CARD8) can coordinate innate and adaptive immune responses and sensitize cells to apoptosis, which may participate in tumorigenesis of virus-induced hepatocellular carcinoma (HCC) and cervical cancer. By bioinformatics analyses, we identified several single nucleotide polymorphisms (SNPs) within a new identified long non-coding RNA (lncRNA) as expression quantitative trait loci (eQTLs) for CARD8. In this study, we therefore hypothesized that CARD8 eQTLs SNPs within lncRNA may influence the risk of HCC and cervical cancer. We performed two independent case-control studies of 1,300 cases with HBV-positive HCC and 1,344 normal controls, together with 1,486 cervical cancer patients and 1,536 control subjects to test the association between eQTLs SNP (rs7248320) for CARD8 and the risk of HCC and cervical cancer. The variant genotype of rs7248320 was significantly associated with increased risk of HCC and cervical cancer [GG vs. AA/GA: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.03-1.61, P = 0.028 for HCC; adjusted OR = 1.34, 95% CI = 1.09-1.66, P = 0.006 for cervical cancer]. Moreover, the effect of rs7248320 on cervical cancer risk was more prominent in premenopausal women. Further interactive analysis detected a significantly multiplicative interaction between rs7248320 and menopausal status on cervical cancer risk (P = 0.018). These findings suggest that CARD8 eQTLs SNP may serve as a susceptibility marker for virus-related HCC and cervical cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
CARD Signaling Adaptor Proteins / genetics*
Carcinoma, Hepatocellular* / epidemiology
Carcinoma, Hepatocellular* / genetics
Carcinoma, Hepatocellular* / metabolism
Female
Gene Expression Regulation, Neoplastic*
Hepatitis B* / complications
Hepatitis B* / epidemiology
Hepatitis B* / genetics
Hepatitis B* / metabolism
Humans
Liver Neoplasms* / epidemiology
Liver Neoplasms* / genetics
Liver Neoplasms* / metabolism
Male
Middle Aged
Neoplasm Proteins / genetics*
Polymorphism, Single Nucleotide*
Premenopause
Quantitative Trait Loci*
RNA, Long Noncoding* / biosynthesis
RNA, Long Noncoding* / genetics
RNA, Neoplasm* / biosynthesis
RNA, Neoplasm* / genetics
Risk Factors
Uterine Cervical Neoplasms / epidemiology
Uterine Cervical Neoplasms / genetics
Uterine Cervical Neoplasms / metabolism

Substances

CARD Signaling Adaptor Proteins
CARD8 protein, human
Neoplasm Proteins
RNA, Long Noncoding
RNA, Neoplasm

Grants and funding

This work was supported by National Natural Science Fund from the National Natural Science Foundation of China (81172757); National Science Foundation for Distinguished Young Scholars of China (81225020); National Natural Science Fund from the National Natural Science Foundation of China (81373079); Foundation of Jiangsu Province for Distinguished Young Scholars (BK2012042); National Key Basic Research Program For Youth (2013CB911400); Foundation for the Program for New Century Excellent Talents in University (NCET-10-0178); National Program for Support of Top-notch Young Professionals; Jiangsu Province Clinical Science and Technology Projects (BL2012008); Collaborative Innovation Center For Cancer Personalized Medicine in Jiangsu Province and the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine); National Natural Science Fund from the National Natural Science Foundation of China(30901236); Beijing Natural Science Foundation (7123225); Beijing Nova Program (xx2012067); Scientific Research Foundation for Returned Scholars, Ministry of Education of China for the conduct of the research and preparation of the article. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.