Correlative polymorphism of NAD(P)H: quinone oxidoreductase (NQO1) with telomere shortening in colorectal cancer.
OBJECTIVE
The aim of this study was to examine whether and relationships could be found among polymorphism of the NQO1 gene, telomere length and telomerase activity in colorectal cancers.


METHODS
Fifty-one invasive colorectal cancers were studied. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was undergone to detect mutation of the NQO1 gene. Telomere length was examined by Southern blot analysis. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications.


RESULTS
Of the 51 tumors, 20 (39.2%) and 9 (17.6%) were heterozygous and homozygous for the mutation, respectively. Most of the cases homozygous for the mutation (88.9%) showed short telomeres and its frequency was significantly higher than in those heterozygous (p = 0.0432). However no relationship was found between the telomerase activity and mutation in the NQO1 gene.


CONCLUSIONS
Our data suggest that oxidative stress by the lack of NQO1 activity could result in telomere shortening through colorectal cancinogenesis.
Takagi
Sho
S
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai 980-8574, Japan. stakagi@int3.med.tohoku.ac.jp
Kinouchi
Yoshitaka
Y
Hiwatashi
Nobuo
N
Hirai
Masashi
M
Suzuki
Susumu
S
Takahashi
Seiichi
S
Negoro
Kenichi
K
Obana
Nobuya
N
Shimosegawa
Tooru
T
D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D019098:Telomerase