XPD codon 312 and 751 polymorphisms, and AFB1 exposure, and hepatocellular carcinoma risk.
BACKGROUND
Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1). In this study, we have focused on the polymorphisms of xeroderma pigmentosum complementation group D (XPD) codon 312 and 751 (namely Asp312Asn and Lys751Gln), involved in nucleotide excision repair.


METHODS
We conducted a case-control study including 618 HCC cases and 712 controls to evaluate the associations between these two polymorphisms and HCC risk for Guangxi population by means of TaqMan-PCR and PCR-RFLP analysis.


RESULTS
We found that individuals featuring the XPD genotypes with codon 751 Gln alleles (namely XPD-LG or XPD-GG) were related to an elevated risk of HCC compared to those with the homozygote of XPD codon 751 Lys alleles [namely XPD-LL, adjusted odds ratios (ORs) were 1.75 and 2.47; 95% confidence interval (CIs) were 1.30-2.37 and 1.62-3.76, respectively]. A gender-specific role was evident that showed an higher risk for women (adjusted OR was 8.58 for XPD-GG) than for men (adjusted OR = 2.90 for XPD-GG). Interestingly, the interactive effects of this polymorphism and AFB1-exposure information showed the codon 751 Gln alleles increase the risk of HCC for individuals facing longer exposure years (Pinteraction = 0.011, OR = 0.85). For example, long-exposure-years (> 48 years) individuals who carried XDP-GG had an adjusted OR of 470.25, whereas long-exposure-years people with XDP-LL were at lower risk (adjusted OR = 149.12). However, we did not find that XPD codon 312 polymorphism was significantly associated with HCC risk.


CONCLUSIONS
These findings suggest that XPD Lys751Gln polymorphism is an important modulator of AFB1 related-HCC development in Guangxi population.
Long
Xi Dai
XD
Department of Pathology, Youjiang Medical College for Nationalities, Baise, Guangxi Zhuang Autonomous Region, PR China. xiaolonglong200166@yahoo.com.cn
Ma
Yun
Y
Zhou
Yun Feng
YF
Yao
Jin Guang
JG
Ban
Fu Zhi
FZ
Huang
Yong Zhi
YZ
Huang
Bing Cheng
BC
D000328:Adult; D016604:Aflatoxin B1 / Q000009:adverse effects*; D000368:Aged; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006509:Hepatitis B / Q000150:complications / Q000453:epidemiology; D006526:Hepatitis C / Q000150:complications / Q000453:epidemiology; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D016604:Aflatoxin B1; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human