Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Carcinog. 2014 Jul;53(7):548-56. doi: 10.1002/mc.22006. Epub 2013 May 16.

Heme-related gene expression signatures of meat intakes in lung cancer tissues.

Author information

1
Cancer Prevention Fellowship Program, Office of Preventive Oncology, Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health (NIH), DHHS, Bethesda, Maryland; Division of Cancer Epidemiology and Genetics, Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health (NIH), DHHS, Bethesda, Maryland.

Abstract

Lung cancer causes more deaths worldwide than any other cancer. In addition to cigarette smoking, dietary factors may contribute to lung carcinogenesis. Epidemiologic studies, including the environment and genetics in lung cancer etiology (EAGLE), have reported increased consumption of red/processed meats to be associated with higher risk of lung cancer. Heme-iron toxicity may link meat intake with cancer. We investigated this hypothesis in meat-related lung carcinogenesis using whole genome expression. We measured genome-wide expression (HG-U133A) in 49 tumor and 42 non-involved fresh frozen lung tissues of 64 adenocarcinoma EAGLE patients. We studied gene expression profiles by high-versus-low meat consumption, with and without adjustment by sex, age, and smoking. Threshold for significance was a false discovery rate (FDR) ≤ 0.15. We studied whether the identified genes played a role in heme-iron related processes by means of manually curated literature search and gene ontology-based pathway analysis. We found that gene expression of 232 annotated genes in tumor tissue significantly distinguished lung adenocarcinoma cases who consumed above/below the median intake of fresh red meats (FDR = 0.12). Sixty-three (∼ 28%) of the 232 identified genes (12 expected by chance, P-value < 0.001) were involved in heme binding, absorption, transport, and Wnt signaling pathway (e.g., CYPs, TPO, HPX, HFE, SLCs, and WNTs). We also identified several genes involved in lipid metabolism (e.g., NCR1, TNF, and UCP3) and oxidative stress (e.g., TPO, SGK2, and MTHFR) that may be indirectly related to heme-toxicity. The study's results provide preliminary evidence that heme-iron toxicity might be one underlying mechanism linking fresh red meat intake and lung cancer.

KEYWORDS:

gene expression; heme-iron; lung cancer

PMID:
23681825
PMCID:
PMC4152901
DOI:
10.1002/mc.22006
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center