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Polymorphisms in base-excision & nucleotide-excision repair genes & prostate cancer risk in north Indian population.

Mandal RK, Gangwar R, Kapoor R, Mittal RD - Indian J. Med. Res. (2012)

Bottom Line: Diplotype analysis of XPC PAT and exon 15 revealed that the frequency of the D-C and I-A diplotype was statistically significant in PCa.The variant genotypes of NER genes were also associated with high Gleason grade.The results indicated that there was a significant modifying effect on the association between genotype XPC PAT and exon 15 polymorphism and PCa risk which was further confirmed by diplotype analysis of XPC PAT and exon 15 in north Indian population.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology & Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

ABSTRACT

Background & objectives: Genetic variation in the DNA repair genes might be associated with altered DNA repair capacities (DRC). Reduced DRC due to inherited polymorphisms may increase the susceptibility to cancers. Base excision and nucleotide excision are the two major repair pathways. We investigated the association between two base excision repair (BER) genes (APE1 exon 5, OGG1 exon 7) and two nucleotide excision repair (NER) genes (XPC PAT, XPC exon 15) with risk of prostate cancer (PCa).

Methods: The study was designed with 192 histopathologically confirmed PCa patients and 224 age matched healthy controls of similar ethnicity. Genotypes were determined by amplification refractory mutation specific (ARMS) and PCR-restriction fragment length polymorphism (RFLP) methods.

Results: Overall, a significant association in NER gene, XPC PAT Ins/Ins (I/I) genotype with PCa risk was observed (Adjusted OR- 2.55, 95%CI-1.22-5.33, P=0.012). XPC exon 15 variant CC genotypes presented statistically significant risk of PCa (Adjusted OR- 2.15, 95% CI-1.09-4.23, P=0.026). However, no association was observed for polymorphism with BER genes. Diplotype analysis of XPC PAT and exon 15 revealed that the frequency of the D-C and I-A diplotype was statistically significant in PCa. The variant genotypes of NER genes were also associated with high Gleason grade.

Interpretation & conclusions: The results indicated that there was a significant modifying effect on the association between genotype XPC PAT and exon 15 polymorphism and PCa risk which was further confirmed by diplotype analysis of XPC PAT and exon 15 in north Indian population.

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Representative gel picture of XPC exon 15 (A>C) polymorphism. Lane 1: 50bp ladder, Lane 2: wild (AA), Lane 3: hetero (AC), Lane 4: variant (CC).
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Figure 4: Representative gel picture of XPC exon 15 (A>C) polymorphism. Lane 1: 50bp ladder, Lane 2: wild (AA), Lane 3: hetero (AC), Lane 4: variant (CC).

Mentions: DNA extraction and genotype analysis: Standard venipuncture was used to collect five ml of peripheral blood in EDTA tubes. Genomic DNA was extracted from the stored peripheral blood by salting out method12. Genotyping were performed using amplification refractory mutation specific (ARMS) PCR methodology for OGG1 exon 7 (C>G) and APE1 exon 5 (T>G)1314. Polymerase chain reaction (PCR) were used to amplify regions of XPC-PAT15. XPC exon 15 (A>C) was genotyped by PCR-RFLP method using PvuII (New England Biolabs, Beverly, MA, USA) restriction enzyme, as shown in Figs 1–4 respectively. All the four gene polymorphisms were successfully genotyped in 224 controls and 192 PCa patients.


Polymorphisms in base-excision & nucleotide-excision repair genes & prostate cancer risk in north Indian population.

Mandal RK, Gangwar R, Kapoor R, Mittal RD - Indian J. Med. Res. (2012)

Representative gel picture of XPC exon 15 (A>C) polymorphism. Lane 1: 50bp ladder, Lane 2: wild (AA), Lane 3: hetero (AC), Lane 4: variant (CC).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3307187&req=5

Figure 4: Representative gel picture of XPC exon 15 (A>C) polymorphism. Lane 1: 50bp ladder, Lane 2: wild (AA), Lane 3: hetero (AC), Lane 4: variant (CC).
Mentions: DNA extraction and genotype analysis: Standard venipuncture was used to collect five ml of peripheral blood in EDTA tubes. Genomic DNA was extracted from the stored peripheral blood by salting out method12. Genotyping were performed using amplification refractory mutation specific (ARMS) PCR methodology for OGG1 exon 7 (C>G) and APE1 exon 5 (T>G)1314. Polymerase chain reaction (PCR) were used to amplify regions of XPC-PAT15. XPC exon 15 (A>C) was genotyped by PCR-RFLP method using PvuII (New England Biolabs, Beverly, MA, USA) restriction enzyme, as shown in Figs 1–4 respectively. All the four gene polymorphisms were successfully genotyped in 224 controls and 192 PCa patients.

Bottom Line: Diplotype analysis of XPC PAT and exon 15 revealed that the frequency of the D-C and I-A diplotype was statistically significant in PCa.The variant genotypes of NER genes were also associated with high Gleason grade.The results indicated that there was a significant modifying effect on the association between genotype XPC PAT and exon 15 polymorphism and PCa risk which was further confirmed by diplotype analysis of XPC PAT and exon 15 in north Indian population.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology & Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

ABSTRACT

Background & objectives: Genetic variation in the DNA repair genes might be associated with altered DNA repair capacities (DRC). Reduced DRC due to inherited polymorphisms may increase the susceptibility to cancers. Base excision and nucleotide excision are the two major repair pathways. We investigated the association between two base excision repair (BER) genes (APE1 exon 5, OGG1 exon 7) and two nucleotide excision repair (NER) genes (XPC PAT, XPC exon 15) with risk of prostate cancer (PCa).

Methods: The study was designed with 192 histopathologically confirmed PCa patients and 224 age matched healthy controls of similar ethnicity. Genotypes were determined by amplification refractory mutation specific (ARMS) and PCR-restriction fragment length polymorphism (RFLP) methods.

Results: Overall, a significant association in NER gene, XPC PAT Ins/Ins (I/I) genotype with PCa risk was observed (Adjusted OR- 2.55, 95%CI-1.22-5.33, P=0.012). XPC exon 15 variant CC genotypes presented statistically significant risk of PCa (Adjusted OR- 2.15, 95% CI-1.09-4.23, P=0.026). However, no association was observed for polymorphism with BER genes. Diplotype analysis of XPC PAT and exon 15 revealed that the frequency of the D-C and I-A diplotype was statistically significant in PCa. The variant genotypes of NER genes were also associated with high Gleason grade.

Interpretation & conclusions: The results indicated that there was a significant modifying effect on the association between genotype XPC PAT and exon 15 polymorphism and PCa risk which was further confirmed by diplotype analysis of XPC PAT and exon 15 in north Indian population.

Show MeSH
Related in: MedlinePlus