Combined effects of polymorphisms of DNA-repair protein genes and metabolic enzyme genes on the risk of cholangiocarcinoma.
OBJECTIVE
Although Opisthorchis viverrini is a risk factor for cholangiocarcinoma, not all the infected individuals develop cholangiocarcinoma. We investigated whether the base excision repair enzyme gene polymorphisms with differentiated repair capacities of inflammation-related deoxyribonucleic acid damage may play a key role and such possible effects from those genes may be increased or diminished in co-existence of polymorphisms of metabolic enzymes, including glutathione-S-transferases mu 1 and glutathione-S-transferases θ1.


METHODS
We genotyped five non-synonymous single-nucleotide polymorphisms of three genes, including the human homolog of the 8-oxoguanine glycosylase 1 Ser326Cys, X-ray repair cross-complementing protein 1 Arg194Trp, Arg280His and Arg399Gln and poly (adenosine diphosphate ribose) polymerase 1 Val762Ala in 87-94 matched case-control pairs, and examined relations between those polymorphisms and the risk of cholangiocarcinoma.


RESULTS
Any single polymorphism did not have a measurable association with the risk of cholangiocarcinoma. However, when considering glutathione-S-transferases mu 1 polymorphism together, the human homolog of the 8-oxoguanine glycosylase 1 codon 326 polymorphism was related to the decreased risk; odds ratios were 1.00 (reference), 0.06 (95% confidence interval 0.01-0.53), 0.06 (0.01-0.54) and 0.14 (0.02-1.08) for persons with human homolog of the 8-oxoguanine glycosylase 1 Ser/Ser and glutathione-S-transferases mu 1 wild, ones with Ser/Ser and glutathione-S-transferases mu 1 null, ones with Ser/Cys or Cys/Cys and glutathione-S-transferases mu 1 wild and ones with Ser/Cys or Cys/Cys and glutathione-S-transferases mu 1 null, respectively (P for interaction <0.01). Further adjustment for the presence of anti-Opisthorchis viverrini antibody, smoking and alcohol drinking did not change the decreased risk. Other combinations of deoxyribonucleic acid-repair gene polymorphism and glutathione-S-transferases were not associated with the risk of cholangiocarcinoma.


CONCLUSIONS
The present findings suggested that decreased capacity of deoxyribonucleic acid-repair gene, human homolog of the 8-oxoguanine glycosylase 1, may be related to decreased risk if much damaged cells die before malignant transformation.
*Department of Paediatrics, National Hospital Organization Fukuoka National Hospital, 1-39-4 Yakatabaru, Minami-ku, Fukuoka 811-1394, Japan. satoshihonjo@hotmail.com.
Lu
L
Zeng
Gyokukou
G
You
Hideaki
H
Tanaka
Petcharin
P
Srivatanakul
Emi
E
Ohta
Chutiwan
C
Viwatthanasittiphong
Mantana
M
Matharit
Dhiraphol
D
Chenvidhya
Adisorn
A
Jedpiyawongse
Masakazu
M
Tanaka
Takahiro
T
Fujii
Banchob
B
Sripa
Kazuhiko
K
Ohshima
Masanao
M
Miwa
Satoshi
S
Honjo
D000409:Alanine; D001120:Arginine; D001650:Bile Duct Neoplasms / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000235:genetics*; D003545:Cysteine; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005838:Genotype; D005973:Glutamine; D005982:Glutathione Transferase / Q000235:genetics; D006639:Histidine; D006801:Humans; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D012694:Serine; D014633:Valine; D000076105:X-ray Repair Cross Complementing Protein 1
D000409:Alanine; D001120:Arginine; D003545:Cysteine; D045647:DNA Glycosylases; D004268:DNA-Binding Proteins; D005973:Glutamine; D005982:Glutathione Transferase; D006639:Histidine; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D012694:Serine; D014633:Valine; D000076105:X-ray Repair Cross Complementing Protein 1; C499320:PARP1 protein, human; C413545:glutathione S-transferase T1; C479058:oxoguanine glycosylase 1, human
GI-hepatobiliary-basic; carcinogenesis; epidemiology-prevention; genetics-carcinogenesis