Absence of correlation between serum CRP levels and mitochondrial D-loop DNA mutations in gastro-oesophageal adenocarcinoma.
BACKGROUND
Both inflammation and mitochondrial DNA (mtDNA) mutation are thought to play a role in the many human cancers. The aim of this study was to evaluate the relationship between inflammation and accumulation of mitochondrial DNA (mtDNA) mutations in the D-loop region in carcinogenesis of gastro-oesophageal adenocarcinomas.


METHODS
Blood samples of 20 patients with gastro-oesophageal adenocarcinoma were taken for measurement of serum C-reactive protein (CRP) concentration. Direct sequencing of mtDNA in the D-loop region was done in the 20 adenocarcinoma samples and their corresponding surrounding non-cancerous tissue. Sequences were compared with existing mtDNA databases to identify mutations.


RESULTS
mtDNA mutations in the D-loop region occur commonly with almost identical frequency in both non-cancerous tissue (3.0 ± 1.6) and adenocarcinoma (3.1 ± 1.9) (P = 0.916, paired t-test). CRP levels are not predictive of the number of D-loop mutations in both adenocarcinoma (β: -0.131; 95% CI: -2.354-1.364; P = 0.583) and non-cancerous tissue samples (β: 0.130; 95% CI: -1.125-1.933; P = 0.586). Five new mutations were identified that were not recorded previously in mtDNA databases.


CONCLUSIONS
D-loop mtDNA mutations are common in both gastro-oesophageal adenocarcinoma and surrounding non-cancerous tissue. However, the accumulation of such mutations appears to occur independent of systemic inflammation. The frequency of D-loop mutations is likely not useful as a marker for carcinogenesis in gastro-oesophageal adenocarcinoma.
Clinical and Surgical Sciences (Surgery), University of Edinburgh, Royal Infirmary, Edinburgh, United Kingdom.
Benjamin H L
BH
Tan
Richard J E
RJ
Skipworth
Nicholas M
NM
Wheelhouse
Kenneth C H
KC
Fearon
James A
JA
Ross
D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D004272:DNA, Mitochondrial; D004938:Esophageal Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology
D004272:DNA, Mitochondrial; D002097:C-Reactive Protein