3 years ago

A cis -eQTL genetic variant of the cancer–testis gene CCDC116 is associated with risk of multiple cancers

Zhibin Hu, Yue Jiang, Lihua Wang, Cheng Wang, Juncheng Dai, Mingtao Huang, Meng Zhu, Fei Yu, Hongbing Shen, Chen Wu, Qun Lu, Dongxin Lin, Tongtong Huang, Hongxia Ma, Na Qin, Guangfu Jin

Abstract

Recent studies have found that cancer–testis (CT) genes, which are expressed predominantly in germ and cancer cells, may be candidate cancer drivers. Because of their crucial roles, genetic variants in these genes may contribute to the development of cancer. Here, we systematically evaluated associations of common variants in CT genes and their promoters for the risk of lung cancer in our initial GWAS (2331 cases and 3077 controls), followed by in silico replication using additional 10,512 lung cancer cases and 9562 controls. We found a significant association between rs3747093 located in the CCDC116 promoter and lung cancer risk (OR = 0.91, P meta = 7.81 × 10−6). Although CCDC116 was expressed at lower levels in somatic tissues compared to the testis, the protective allele A of rs3747093 was associated with decreased CCDC116 expression in many normal tissues, including the lung (P = 8.1 × 10−13). We subsequently genotyped this variant in another four commonly diagnosed cancers (gastric, esophageal, colorectal, and breast cancers), as we found expression quantitative trait locus (eQTL) signals for rs3747093 and CCDC116 in their corresponding normal tissues. Interestingly, we observed consistent associations between rs3747093 and multiple cancers (gastric cancer: OR = 0.85, P = 2.21 × 10−4; esophageal cancer: OR = 0.91, P = 2.57 × 10−2; colorectal cancer: OR = 0.80, P = 1.85 × 10−6; and breast cancer: OR = 0.87, P = 1.55 × 10−3). Taken together, the A allele of rs3747093 showed significant protective effects on cancer risk (OR = 0.88, P pool = 6.52 × 10−13) in an Asian population. Moreover, our findings suggest that low abundance expression of CT genes in normal tissues may also contribute to tumorigenesis, providing a new mechanism of CT genes in the development of cancer.

Publisher URL: https://link.springer.com/article/10.1007/s00439-017-1827-2

DOI: 10.1007/s00439-017-1827-2

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.