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.

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.