Mitochondrial DNA haplogroup M is associated with late onset of hepatocellular carcinoma

Abstract

Abstract. The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been associated with various types of cancer. The association of SNPs with cancer risk and disease outcome has been exhaustively studied. In this study, we investigated the association of age-at-onset and SNPs in the mitochondrial D-loop using a population-based series of hepatocellular carcinoma (HCC) patients. Haplogroup M (489C) and allele 235G were identified for their association with the late onset of HCC by the log-rank test. In an overall multivariate analysis, haplogroup M (489C) was identified as an independent predictive factor for the age-at-onset of HCC at borderline significant levels [relative risk, 1.736; 95% confidence interval (CI), 0.967-3.115; p= 0.065]. Genetic polymorphisms in the D-loop are predictive markers for age-at-onset in HCC patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help to identify HCC patient subgroups at high risk of early onset of the disease.

Elevated level of some chemokines in plasma of gastric cancer patients

“…Numerous studies were undertaken to find specific “markers” of gastric cancer progression to improve diagnostic procedure. The most promising data suggests that the production of SDF-1α in the primary cancer may be such a prognostic factor [10]. High CXCR4/high SDF-1α (CXCL12) expression in tumour cells is significantly associated with depth of cancer invasion, lymph node involvement, and more advanced stage of disease [10].…”

“…The most promising data suggests that the production of SDF-1α in the primary cancer may be such a prognostic factor [10]. High CXCR4/high SDF-1α (CXCL12) expression in tumour cells is significantly associated with depth of cancer invasion, lymph node involvement, and more advanced stage of disease [10]. Also, elevated level of RANTES (CCL5) in serum of gastric cancer patients correlates with poor prognosis [11].…”

Single nucleotide polymorphisms in the mitochondrial displacement loop and age at onset of non-Hodgkin lymphoma

“…We have previously identified age at onset-associated SNPs of the D-loop, in patients with hepatocellular carcinoma and esophageal squamous carcinoma 28,29. In this study, we also identified age at onset-associated SNPs in NHL patients.…”

Identification of sequence polymorphisms in the displacement loop region of mitochondrial DNA as a risk factor for renal cell carcinoma

“…In our study, all the cancer risk-associated SNPs were identified in the HV segment region of the D-loop, with nucleotides 16293, 16298 and 16319 belonging to HV-Ⅰ, 262 to HV-Ⅱ and 488 to HV-Ⅲ. Cancer risk-and outcome-associated SNPs were identified in these regions in other types of cancer as well, including esophageal squamous cell carcinoma (17,27) and hepatocellular carcinoma (25,26). The HV segments are mutational hotspots at which germline and tumor mtDNA mutations preferentially occur (28).…”