DOI: https://doi.org/10.

53350/pjmhs22166528
ORIGINAL ARTICLE

Study of XPD Gene Polymorphism in HCV Positive HCC Egyptian Patients

BOTHAINA MADKOUR1, OLA MAHMOUAD1, OMAR M.SABRY1, AHMED R. MASHAAL2, MOHAMED A. EL-REFAIY2 AND RABAB
FOUAD1
1
Department of Haematology, Theodor Bilharz Research Institute, Giza, Egypt.
2
Department of Tropical Medicine, Theodor Bilharz Research Institute, Giza, Egypt.
Corresponding author: E-mail: [email protected].

ABSTRACT
Background: Hepatocellular carcinoma (HCC) is one of the most frequently occurring tumorous cells globally, but its
pathogenesis is unknown. Xeroderma pigmentosum gene D (XPD) is a critical Repair of DNA gene that has been implicated in
protein mutation.
Aim: The objectives of this research were to assess the relationship between the XPD gene polymorphism (rs13181) (codon
751, Lys to Gln) and susceptibility to hepatocellular neoplasms, as well as to investigate the relationship between HCV and XPD
polymorphisms.
Methods: Seventy-nine HCC patients and 63 patients with active HCV infection, and 52 healthy controls were involved. Real-
time PCR carried out for genotyping of XPD Lys751Gln (rs 13181).
Results: Patients with XPD Lys751Gln AC genotype have a great risk of HCC development (p = 0.01, OR =1.505).
Conclusion: Our finding was that XPD Lys751Gln (A/C) polymorphism exhibit a major function in HCC early detection
susceptibility in Egyptian patients. It has the potential to be a valuable noninvasive molecular indicator for evaluating the HCC
threat.
Keywords: HCC; RT-PCR; XPD gene polymorphism

INTRODUCTION Genomic DNA extraction: The QIAamp DNA Mini Kit was utilized
Hepatocellular carcinoma (HCC), the much more commonly to collect genomic DNA (Qiagen; catalog No.: 51104). Proteinase
reported liver tumor, substantially leads to global tumor-related K is utilized to remove DNA from whole blood. Cells are lysed after
mortality and morbidity. The annual occurrence of new HCC a brief incubation with proteinase K and a unique lysis buffer
patients is reported to be greater than 0.5 million1. containing guanidine HCL that inactivates all nucleases
It is well-founded that HCC production is a complicated immediately. Cellular nucleic acids adhere selectively to pre-
biological function, and the exact mechanisms by which HCC packaged specific glass fibers in a highly pure filter tube. To
occurs are still unknown. Numerous risk factors, including aflatoxin remove PCR impurities, a sequence of rapid "wash - and - spin"
B1 (AFB1) consumption, smoking, chronic hepatitis B virus (HBV) steps is performed using 500 ul of Buffer AW1 and AW2. Finally,
infection, and more alcohol use, all lead to HCC susceptibility. elution buffer (200 ul Buffer AE) was applied, and the mixture was
Along with these causes, genetic polymorphisms contribute incubated at 15-25 C for 1 minute to liberate the nucleic acid from
significantly to HCC susceptibility2. the glass fiber, which is critical for removing PCR impurities.
Numerous reports conducted over the last few decades have Multiplication of the extracted DNA and detection of
assessed and illustrated the relationship between repair of DNA polymorphism: Allelic Discrimination (AD) is a multiplexed and
genes and susceptibility to hepatocellular neoplasms. The most end-point (data are obtained after the PCR process) test for
effective repair of the DNA pathway has been suggested to be detecting variants in a single nucleic acid sequence. The presence
nucleotide excision repair (NER). Xeroderma pigmentosum of two primer/probe pairs in every interaction enables genotyping
complementary class D (XPD) is a gene positioned on of the two potential variations at a desired template sequence's
chromosome 19q13.3 that encodes a NER enzyme3. single-nucleotide polymorphism (SNP) site. Allelic discrimination
XDP affects the NER pathway since it is required to open the tests employ a PCR test that involves a fluorescent dye-labeled
DNA duplex required to excise the DNA fragment comprising the probe specific for each allele. The probes include two distinct
deterioration base4. fluorescent reporter dyes (FAM and VIC®) that differentiate allele
The XPD Lys751Gln (rs13181) polymorphism was multiplication. Every probe anneals to the complementary
demonstrated to influence repair of DNA ability, likely by modifying sequences between the reverse and forward primer locations
the amino acid sequence of the XPD protein, resulting in throughout PCR. Only probes that hybridize to the allele can be
decreased repair ability and a raised tumor threat5. cleaved by AmpliTaq Gold® DNA polymerase. Cleavage
distinguishes the reporter dye from the quencher dye, resulting in
an improvement in the reporter dye's fluorescence. Therefore, the
PATIENTS AND METHODS
fluorescence signal(s) produced by PCR multiplication identifies
Study population: This research was performed in the Tropical
the existence of alleles in the specimen.
department of Theodor Bilharz Research Institute (TBRI), with 194
Mismatches between a probe and an allele minimize probe
participants classified into three groups: group A included 79
hybridization performance. Additionally, rather than cleaving the
cases with HCC, while group B involved 63 patients with Active
mismatched probe to release reporter dye, AmpliTaq Gold DNA
HCV infection. Eventually, group C included 52 age and sex-
polymerase is more likely to displace it.
matched volunteers as a control group. Participants with co-
Each PCR test included 2.5 ul diluted DNA, 12.5 ul of
infections with HBV, alcohol use, or antiviral treatment were
TaqMan Universal PCR Master Mix, 1.25 ul 20 TaqMan
excluded from the sample. Patients that were involved in the
Genotyping Test Mix, and 8.75 ul distilled water. This PCR test
research had informed consent. Additionally, the TBRI ethics
was performed in a thermal cycler equipped with an ABI 7500, and
committee approved these measures in compliance with the
the following software can be seen in Table 1.
Declaration of Helsinki.
Table 1: PCR amplification run
Pre-Read Run Multiplication (RQ-PCR program) Post-Read Run
1 Cycle Temperature 1 Cycle Cycles 1 Cycle
60 °C 1 min. 95°C 10 min X1 60 °C 1 min
95°C 15 sec X40
60°C 60°C

528 P J M H S Vol. 16, No. 06, Jun 2022

 B. Madkour, O. Mahmouad, O. M.Sabry et al

Statistical analysis: Microsoft Excel 2010 and the statistical RESULTS

package for social science (SPSS version 26.0) for Windows will We found that there was a significant rise in AC hetero genotype in
be utilized to analyze the results (SPSS IBM., Chicago, IL). HCC group (45.6%) than HCV group (31.7%) (OR =1.505, 95% CI
Continuous normally dispersed variations were demonstrated as = 0.743 - 3.048, p= 0.01). Also, there was a significant rise in
mean ± SD with a 95 % confidence level, non-normally dispersed mutant genotypes (AC+CC) in HCC group (54.4%) in comparison
variations as median with a 25 and 75 percentile, and categorical to HCV group (41.3%) (OR = 1.419, 95% CI = 0.730 - 2.759, p=
variations as frequencies and percentages; a p-value <0.05 was 0.01).Though, there was insignificant difference in allele
considered statistically significant. The Student's t-test was utilized frequencies between the control group and HCV group or HCC
to compare the means of normally dispersed differences between group regarding the genotypes frequency of the XDP gene.
classes; the Mann-Whitney assay was utilized to compare non- Moreover, the mutant C allele was greater in HCC patients (50%),
normal aspects, and the 2 test or Fisher's exact assay was utilized although this rise is statistically insignificant. Wild genotype (AA)
to compare the distributions of categorical differences between was significantly greater in the HCV group than the HCC group
classes. (p=0.01) (Table 2).

Table (2): Genotypes frequency of XDP gene among studied groups.

CONTROL HCV HCC P. value
n=52 n=63 n=79 HCV Vs Control HCC Vs Control HCC Vs HCV
AA wild 27 (51.9%) 37 (58.7 %) 36 (45.6 %) 0.2 0.2 0.01*
AC heter 19 (36.5 %) 20 (31.7 %) 36 (45.6 %) 0.3 0.1 0.01*
CC homo 6 (11.5 %) 6 (9.5 %) 7 (8.9 %) 0.5 0.3 0.8
AC+CC 25(48.1 %) 26(41.3 %) 43(54.4 %) 0.2 0.2 0.01*
A (wild) 73(0.702) 94(0.746) 108(0.684)
Allele 0.3 0.7 0.2
C(mutant) 31(0.298) 32(0.254) 50(0.316)
*P value ≤ 0.05 significant; **P value ≤ 0.01 greatly significant.

Hardy-Weinberg Equilibrium: Regarding HCV patients, statistically non-significant differences were presented between the frequencies of
observed and expected genotypes.
This proved that the XPD genotypes of the randomly collected samples were in H-W equilibrium data. (Table 3).

Table 3: Comparison between Observed and Expected SNPs Genotypes for HCV patients.
Observed results Expected results
SNPs Genotype n=63 p. value
(Current Study) (H-W equilibrium)
XPD AA 37 0.587 0.410 0.7
AG 20 0.317 0.083 0.4
GG 6 0.096 0.507 0.4
Total 63 1.000 1.000
H-W equilibrium = Hardy-Weinberg equilibrium; n=Number,
P. Value is based on the X2 test, *p. value <0.05 is significant, ** p. value <0.01 is greatly significant.

In HCC patients, statistically significant differences were presented in AG genotype between the frequencies of observed and
expected genotypes. This proved that the XPD genotypes of the randomly collected samples were not in H-W equilibrium data (Table 4).

Table 4: Comparison between Observed and Expected SNPs Genotypes for HCC patients.
Observed results Expected results
SNPs Genotype n=79 p. value
(Current Study) (H-W equilibrium)
AA 36 0.456 0.325 0.8
XPD AG 36 0.456 0.042 0.04*
GG 7 0.088 0.633 0.3
Total 79 1.000 1.000
H-W equilibrium = Hardy-Weinberg equilibrium; n=Number,
P. Value is based on the X2 test, *p. value <0.05 is significant, ** p. value <0.01 is greatly significant.

DISCUSSION mechanisms against tumors. Alterations to the human genome's

HCC is prevalent in the world. It has a poor prognosis and a low Repair of DNA mechanisms cause the aggregation of gene
survival rate that necessitates early detection6. mutations and tumor growth11.
Due to the broad heterogeneity of clinical symptoms, Repairing genetic deterioration is critical for humans to avoid
variations in biological activity, multiple factors of liver disease, and developing a lot of symptoms, such as tumors. Numerous studies
multiple therapeutic techniques, HCC care requires a multifaceted have consistently demonstrated inter-individual variance in the
approach7. Repair of DNA ability and that populations with impaired Repair of
Hepatitis viruses have been identified as the primary cause DNA ability are more susceptible to improving tumors. As a result,
of genetic deterioration, with chromosomal instability and genetic variations in the repair of DNA genes that impair repair of
mutations contributing to the production of HCC8. DNA ability are thought to have a major effect on an individual's
Genetic polymorphisms are typically classified as fragment proclivity for tumors12.
length polymorphisms (FLPs), repetitive sequence polymorphisms The complementation class D gene of Xeroderma
(RSPs), or single nucleotide polymorphisms (SNPs)9. pigmentosum encodes an adenosine triphosphate-dependent DNA
Genetic polymorphisms can alter the expression of proteins helicase that mediates DNA unwinding in the 5'-3' direction. The
or the structure of cytokine particles, resulting in a variety of clinical enzyme is needed for the nucleotide excision repair (NER)
symptoms and outcomes for HCC10. mechanism, which would be the primary repair of the DNA route to
Repair of DNA systems is critical for normal cell cycle control eliminate large DNA damages due to compounds, oxidative stress,
and cell integrity preservation and the body's protective and environmental carcinogens13.

P J M H S Vol. 16, No. 06, Jun 2022 529

Study of XPD Gene Polymorphism in HCV Positive HCC Egyptian Patients

SNPs account for approximately 90% of mutations in the those with the AA genotype. Additionally, they found that carriers
human genome, and research has demonstrated that gene of the CC genotype had a more positive result and a lower
mutations can result in altered repair abilities, which can result in mortality rate than carriers of the AA genotype8.
tumors14. Other studies found no connection among the XPD rs13181
Ultraviolet light, ionizing radiation, and various chemical and rs1799793 polymorphisms and gastric tumor28,29, 30.
variations all have the potential to cause double-strand breaks, Additionally, the majority of Caucasian research found no
DNA single, DNA protein cross-linking, base mismatches, and association between these gastric tumors and XPD
other genetic deterioration. The gene repair mechanism can polymorphisms. As a result, current data produced conflicting
correct these DNA errors, thus preserving the genetic information's findings. Numerous meta-analyses were conducted in an early
stability. hMSH2, XPD, XRCC1, hOGG1, and XRCC3 are well- period to analyze the reported data. A meta-analysis study
known fix genes15. demonstrates that the XPD rs13181 and rs1799793
The XPD gene is composed of 23 exons and 6 SNPs. XPD's polymorphisms are related to a gastric tumor in Chinese but not in
primary feature is nucleotide excision16. Nevertheless, as a Caucasians31.
transcription factor II D (TFIID) component, XPD can contribute to Another study proposed that XPD rs1799793 can affect
p53-mediated apoptosis and transcription17. A single base change gastric tumor threat but found no relevant associations for XPD
in XPD will alter the protein's function and result in tumorigenesis18. rs1318132. Another study hypothesized that XPD rs13181 had no
Numerous XPD polymorphisms have been found in the effect on the pathogenesis of gastric tumor33.
coding regions, such as a modification in the amino acid lysine to Nevertheless, some limitations applied to the recent
glutamine in codon 751 (Lys751Gln, rs13181) and a modification in analysis, including the fact that only Egyptians were involved.
the amino acid aspartic acid to asparagine in codon 312 Leading to a shortage of study of gene-environment and gene-to-
(Asp312Asn, rs1799793)19. gene interactions because of insufficient original evidence, we
The Gln allele of XPD rs13181 and the Asn allele of XPD cannot determine the genetic polymorphisms of other repairs of
rs1799793 have been linked to decreased NER ability. Given the DNA genes involved in the NER, like XPC and XPA.
critical role of XPD in repairing DNA, the correlation between XPD
polymorphisms and tumor threat is especially interesting20. CONCLUSION
We investigate the XPD Lys751Gln gene polymorphism and We found that XPD Lys751Gln (A/C) polymorphism had a major
its interaction with HCC in Egyptian patients in recent research. diagnostic function in the early detection of HCC cases. Additional
We discovered a statistically significant rise in the AC genotype research is required to confirm our results, using wider sample size
among HCC cases as compared to HCV cases. Additionally, when and comparing HCV genotype 4 to other genotypes and other
HCC cases were compared to HCV cases, a statistically significant ethnic population.
rise in the frequency of combined (AC + CC) genotypes was
reported, as was a significant rise in the frequency of the mutant C
REFERENCES
allele. 1. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global
EL-Abd et al. found a statistically significant rise in the cancer statistics. CA Cancer J Clin 61: 6990, 2011.
frequency of combined (AC + CC) genotypes and also the mutant 2. Gao J, Xie L, Yang WS, et al: factors of hepatocellular carcinoma
C allele in HCC Egyptian cases when compared to the control current status and perspectives. Asian Pac J Cancer Prev 13:
group 21. 743752, 2012.
Prior research done confirmed our findings. They discovered 3. Flejter WL, McDaniel LD, Johns D, Friedberg EC and Schultz RA:
a major rise in the frequency of the CC genotype in HCC cases Correction of xeroderma pigmentosum complementation D mutant
relative to controls and a major rise in the frequency of the C allele cell phenotypes by chromosome and gene transfer: Involvement of
the human ERCC2 DNA repair gene. Proc Natl Acad Sci USA 89:
in patients compared to controls22. 261265, 1992.
Additionally, another study concurs with our established 4. Manuguerra M, Saletta F, Karagas MR, et al: XRCC3 and
major connection between XPD Lys751Gln (A/C) genotypes and XPD/ERCC2 single nucleotide polymorphisms and the of cancer: A
HCC in aflatoxin-exposed cases. They showed a statistically HuGE review. Am J Epidemiol 164: 297302, 2006.
significant rise in the prevalence of the AC genotype among 5. Wolfe KJ, Wickliffe JK, Hill CE, Paolini M, Ammenheuser MM. Single
patients compared to the control group. Additionally, they nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter
discovered a substantial rise in the population of participants with mRNA expression. Pharmacogenet Genomics. 2007; 17: 897-905.
6. Yao DF, Dong ZZ, Yao M. Specific molecular markers in
the CC genotype as compared to the control group, indicating that hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2007; 6:
populations bearing the XPD codon 751 C allele was at a raised 241-247.
threat of HCC as in comparison to those homozygous for the XPD 7. Abdelaziz AO, Elbaz TM, Shousha HI, Ibrahim MM, Elshazli MA,
codon 751 A allele[23. Abdelmaksoud AH, et al. Survival and prognostic factors for
Some studies found that the XPD rs13181 G allele was hepatocellular carcinoma: an Egyptian multidisciplinary clinic
linked with a raised incidence of gastric tumor in a southern experience. Asian Pac J Cancer Prev. 2014; 15: 3915-3920.
Chinese individual, using a case-control analysis of 361 patients 8. Yue AM, Xie ZB, Guo SP, Wei QD, Yang XW. Implication of
polymorphisms in DNA repair genes in prognosis of hepatocellular
and 616 controls [24]. Additionally, Jiang et al. discovered a carcinoma. Asian Pac J Cancer Prev. 2013; 14: 355-358.
connection between the XPD rs13181 polymorphism and gastric 9. Petta S, Miele L, Bugianesi E, Cammà C, Rosso C, Boccia S, Cabibi
tumor25. D, Di Marco V, Grimaudo S, Grieco A, et al. Glucokinase regulatory
In comparison, an alternate analysis dismissed to detect a protein gene polymorphism affects liver fibrosis in non-alcoholic fatty
meaningful relation between the HCC susceptibility and XPD liver disease. PLoS One. 2014;9:e87523.
Lys751Gln polymorphism, with AA genotypes occurring in 50% of 10. Akhdar H, El Shamieh S, Musso O, Désert R, Joumaa W, Guyader D,
HCC patients, AC genotypes occurring in 38% of HCC patients, Aninat C, Corlu A, Morel F. The rs3957357C>T SNP in GSTA1 is
associated with a higher of occurrence of hepatocellular carcinoma
and CC genotypes occurring in 12% of HCC patients (p = 0.61)26. in european individuals. PLoS One. 2016;11:e0167543.
In contrast to our findings, a meta-analysis of seven 11. Duxin JP, Walter JC. What is the DNA repair defect underlying
reports on the XPD Lys751Gln polymorphism found no correlation Fanconi anemia? Curr Opin Cell Biol. 2015;37:49–60.
to HCC threat for all genetic designs. It recommended additional 12. Alhmoud JF, Woolley JF, Al Moustafa AE, Malki MI. DNA
large-scale tests examining gene-gene/gene-environment damage/repair management in cancers. Cancers (Basel). 2020;
connections to clarify the discrepancy between our findings and 12(4):1050.
those of other reports27. 13. Lehmann AR. The xeroderma pigmentosum D (XPD) gene: one
gene, two functions, three diseases. Genes Dev. 2001;15(1): 15-23.
Some reports discovered a major improvement in the 14. Bharati R, Jenkins MA, Lindor NM, Le Marchand L, Gallinger S, Haile
survival time for individuals with the CC genotype as compared to RW, Newcomb PA, Hopper JL, Win AK. Does of endometrial cancer

530 P J M H S Vol. 16, No. 06, Jun 2022

 B. Madkour, O. Mahmouad, O. M.Sabry et al

for women without a germline mutation in a DNA mismatch repair liver cancer, and colorectal cancer. Chin J Clin Oncol.
gene depend on family history of endometrial cancer or colorectal 2012;39(18):1358-1362.
cancer? Gynecol Oncol. 2014;133:287–292. 25. Long XD, Ma Y, Huang YZ, et al. Genetic polymorphisms in DNA
15. Caldecott KW. DNA single-strand break repair. Exp Cell Res. repair genes XPC, XPD, and XRCC4, and susceptibility to
2014;329:2–8. doi: 10.1016/j.yexcr.2014.08.027. helicobacter pylori infection-related gastric antrum adenocarcinoma in
16. Liu J, Fang H, Chi Z, Wu Z, Wei D, Mo D, Niu K, Balajee AS, Hei TK, Guangxi population, China. Mol Carcinog. 2010;49(6): 611-618.
Nie L, et al: XPD localizes in mitochondria and protects the 26. Gulnaz A, Sayyed AH, Amin F, Khan Au, Aslam MA, Shaikh RS, et
mitochondrial genome from oxidative DNA damage. Nucleic Acids al. Association of XRCC1, XRCC3, and XPD genetic polymorphism
Res 43: 5476-5488, 2015. with an rised of hepatocellular carcinoma because of the hepatitis B
17. Bănescu C, Trifa AP, Demian S, Benedek Lazar E, Dima D, Duicu C and C virus. Eur J GastroenterolHepatol. 2013; 25: 166-179.
and Dobreanu M: Polymorphism of XRCC1, XRCC3, and XPD genes 27. Zhang RC, Mou SH. Polymorphisms of excision repair gene XPD
and of chronic myeloid leukemia. BioMed Res Int 2014: 213790, Lys751Gln and hOGG1 Ser326Cys might not be associated with
2014. hepatocellular carcinoma : a meta-analysis. Tumour Biol. 2013; 34:
18. Li P, Wang YD, Cheng J, Chen JC and Ha MW: Association between 901-907.
polymorphisms of BAG-1 and XPD and chemotherapy sensitivity in 28. Chen Z, Zhang C, Xu C, et al. Effects of selected genetic
advanced non-small-cell lung cancer patients treated with vinorelbine polymorphisms in xeroderma pigmentosum complementary D on
combined cisplatin regimen. Tumour Biol 36: 9465-9473, 2015. gastric cancer. Mol Biol Rep. 2011;38(3):1507-1513.
19. Worrillow L, Roman E, Adamson PJ, Kane E, Allan JM, Lightfoot TJ. 29. He J. Polymorphisms in Nucleotide Excision Repair Genes and
Polymorphisms in the nucleotide excision repair gene ERCC2/XPD Gastric Cancer. Doctoral Dissertation of Fudan University; 2007: 1-
and of non-Hodgkin lymphoma. Cancer Epidemiol. 2009;33(3- 142.
4):257-260. 30. Zhou RM, Li Y, Wang N, Dong XJ, Zhang XJ, Guo W. Correlation
20. Pascale RM, Simile MM, Peitta G, Seddaiu MA, Feo F, Calvisi DF. between single nucleotide polymorphism of DNA repair gene XPD
Experimental models to define the genetic predisposition to liver and the s of esophageal squamous cell carcinoma and gastric
cancer. Cancers (Basel). 2019;11(10):1450. cardiac adenocarcinoma. Tumor. 2007;27(2): 118-122
21. EL-Abd NE, Kamal AM, Siam IM and Shousha HI. Xeroderma 31. Xue H, Lu Y, Lin B, Chen J, Tang F, Huang G. The effect of XPD/
Pigmentosum Complementation D (XPD) Codon 751 and ERCC2 polymorphisms on gastric cancer among different ethnicities:
Exonuclease 1 Glu 589 Lysgene Polymorphismsare Associated with a systematic review and meta-analysis. PLoS One.
Hepatocellular Carcinoma in Egyptian Patients with HCV (Genotype- 2012;7(9):e43431.
4). Austin Virol and Retrovirology. 2016; 3(2): 1022. 32. Yin QH, Liu C, Hu JB, Meng RR, Li L, Wang YJ. XPD Lys751Gln and
22. Guo LY, Jin XP, Niu W, Li XF, Liu BH, Wang YL. Association of XPD Asp312Asn polymorphisms and gastric cancer susceptibility: a meta-
and XRCC1 genetic polymorphisms with hepatocellular carcinoma . analysis of case-control studies. Asian Pac J Cancer Prev.
Asian Pac J Cancer Prev. 2012; 13: 4423-4426. 2013;14(1):231-236.
23. Long XD, Ma Y, Zhou YF, Yao JG, Ban FZ, Huang YZ, et al. XPD 33. Du H, Guo N, Shi B, et al. The effect of XPD polymorphisms on
codon 312 and 751 polymorphisms and AFB1 exposure and digestive tract cancers: a meta-analysis. PLoS One. 2014;
hepatocellular carcinoma . BMC Cancer. 2009; 9: 400. 9(5):e96301.
24. Jiang Y, Yin MW, Yu ZY, Kang YH, Deng JB, Liu B.Relationship of
hOGG1 and XPD gene polymorphisms with the of gastric cancer,

P J M H S Vol. 16, No. 06, Jun 2022 531