No association between genetic polymorphisms in NAD(P)H oxidase p22phox and paraoxonase 1 and colorectal cancer risk.
BACKGROUND
Impaired metabolism of ingested toxic or carcinogenic compounds is a postulated mechanism underlying colorectal cancer (CRC). Furthermore, it is suggested that reactive oxygen species (ROS) may play a role in human cancer development. Polymorphic variations in NAD(P)H oxidase p22phox and paraoxonase 1 (PON1) enzyme activities may alter superoxide production or the rate of chemical metabolism, respectively, and this may influence the risk for CRC. Therefore, this study was designed to determine whether the distribution of polymorphisms in NAD(P)H oxidase p22phox and PON1 genes was different in sporadic CRCpatients versus healthy controls.


METHODS
The study participants (365 cases and 354 controls) were all of Caucasian origin. NAD(P)H oxidase p22phox H72Y, and PON1 L55M and Q192R polymorphisms were genotyped by polymerase chain reaction, eventually followed by restriction-fragment-length-polymorphism analyses.


RESULTS
Comparison of CRC patients and controls revealed no significant differences in genotype distributions or allele frequencies for polymorphisms in the NAD(P)H oxidase p22phox and PON1 genes. Investigation of potential associations between the variant NAD(P)H oxidase p22phox or PON1 alleles and the clinical characteristics, tumour location or tumour stage, also did not reveal statistically significant associations.


CONCLUSIONS
Variant genotypes of NAD(P)H oxidase p22phox and PON1 do not contribute to the susceptibility to CRC.
Van Der Logt
Elise M J
EM
Department of Gastroenterology, University Medical Centre St Radboud, 6500 HB Nijmegen, The Netherlands.
Janssen
Cynthia H J M
CH
Van Hooijdonk
Zairah
Z
Roelofs
Hennie M J
HM
Wobbes
Theo
T
Nagengast
Fokko M
FM
Peters
Wilbert H M
WH
D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009252:NADPH Dehydrogenase / Q000235:genetics*; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human