Association of polymorphism in MDM-2 and p53 genes with breast cancer risk in Indian women.
OBJECTIVE
Single nucleotide polymorphism (SNP) at position -309 (T309G) in MDM-2 promoter induces tumor formation in the individuals possessing inherited p53 mutations. The present study was undertaken to investigate the association of MDM-2 SNP309, p53 Arg72Pro, and p53 intron-6 G/A polymorphism with total, premenopausal, and postmenopausal breast cancer risks in Indian women.


METHODS
Genotyping of MDM-2 SNP309, p53 Arg72Pro, and p53 intron-6 G/A in 104 patients and 105 controls was performed either by ARMS-PCR or by polymerase chain reaction and direct sequencing.


RESULTS
The p53 Arg72Pro heterozygous variant and in combination with its homozygous variant exhibited a significant protective association with total (odds ratio [95% confidence interval]: 0.42 [0.22-0.81] and 0.46 [0.25-0.85], p value; 0.007 and 0.012) and postmenopausal breast cancer risk (odds ratio [95% confidence interval]: 0.25 [0.07-0.73] and 0.27 [0.08-0.77], p value; 0.009 and 0.013]. Neither combined nor homozygous/heterozygous MDM-2 SNP309G was associated with total, premenopausal, or postmenopausal breast cancer risk; however, MDM-2 SNP309G, along with p53 Arg72Pro heterozygous variant, showed a significant protective association with premenopausal breast cancer risk (odds ratio [95% confidence interval]: 0.18 [0.02-1.20], p value; 0.041 for homozygous + heterozygous MDM-2 SNP309G).


CONCLUSIONS
The results indicate protective associations of p53 Arg72Pro heterozygous variant with postmenopausal and MDM-2 SNP309G along with p53 Arg72Pro heterozygous variant with premenopausal breast cancer risk.
Singh
Virendra
V
Industrial Toxicology Research Centre, Lucknow, India.
Rastogi
Neeraj
N
Mathur
Neeraj
N
Singh
Kalpana
K
Singh
Mahendra Pratap
MP
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D006801:Humans; D007194:India; D007438:Introns; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2