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Effects of the single nucleotide polymorphism at MDM2 309 on breast cancer patients with/without BRCA1/2 mutations.

Nechushtan H, Hamburger T, Mendelson S, Kadouri L, Sharon N, Pikarsky E, Peretz T - BMC Cancer (2009)

Bottom Line: This result has been obtained in a relatively small subgroup and is of borderline statistical significance.Interestingly, in the BRCA1/2 mutation carriers, we found a survival advantage for patients harboring the SNP309 G/G genotype (p = 0.0086) but not for the 272 patients not harbouring this mutations.MDM2SNP309G/G main effect on BRCA1/2 positive mutation carriers is linked to its effect on patients survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel. hovavnech@hadassah.org.il

ABSTRACT

Background: A germ line single nucleotide polymorphism (SNP) in the first intron of the gene encoding MDM2 at position 309, an important modulator of p53, has been described. BRCA1/2 mutation have been associated with increased rates of breast cancers with mutated P53. It was shown that the presence of MDM2 309 SNP correlated with younger cancer onset age in individuals with a p53 mutations. The differential effects of this SNP were also linked to estrogen receptor activation. Here we report on our study of 453 Ashkenazi breast cancer patients of whom 180 were positive for the known Ashkenazi BRCA1/2 mutations

Methods: DNA from breast cancer patients was obtained for analysis of one of the three common BRCA1/2 mutations and MDM2 SNP309. Data regarding cancer onset and death ages was obtained from our database and Statistical analysis was performed using the SPSS statistical package (SPCC Inc., Chicago, IL), and JMP software (SAS Institute, Cary, NC).

Results: The percentage of MDM2 SNP309 in control and BRCA 1/2 population which is similar to that reported for other Jewish Ashkenazi populations at 52.2% for the heterozygotes and 25.0% for MDM2SNP309G/G and 22.8% for MDM2SNP309T/T.There was not a statistical significant difference in median age of disease onset in the different MDM2 SNP309 subgroups of the BRCA1/2 carriers. When we further divided the group into under and above 51 years old ( presumed menopause age) in the BRCA1 positive subset we found that there were less patients of the MDM2SNP309 G/G versus the MDM2SNP309 T/T in the over 51 patient group (p = 0.049). This result has been obtained in a relatively small subgroup and is of borderline statistical significance. Interestingly, in the BRCA1/2 mutation carriers, we found a survival advantage for patients harboring the SNP309 G/G genotype (p = 0.0086) but not for the 272 patients not harbouring this mutations.

Conclusion: MDM2SNP309G/G main effect on BRCA1/2 positive mutation carriers is linked to its effect on patients survival. Further research is needed in order to understand the reason for this difference.

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Related in: MedlinePlus

Cancer onset age in the BRCA1/2 mutation carriers (A) and BRCA1/2 non carriers (B), according to their MDM2 SNP-309 subtypes. C and D prevalence of the SNP MDM309 genotypes in women above and bellow 51 years old – C total carrier population and D only BRCA1 mutation carriers.
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Figure 1: Cancer onset age in the BRCA1/2 mutation carriers (A) and BRCA1/2 non carriers (B), according to their MDM2 SNP-309 subtypes. C and D prevalence of the SNP MDM309 genotypes in women above and bellow 51 years old – C total carrier population and D only BRCA1 mutation carriers.

Mentions: There was no significant difference between the prevalence of the different MDM2 SNP309 alleles between the BRCA1/2 patients (Table 2a) and the non carrier group (Table 2b). Disease onset age of breast cancer did seem to vary according to MDM2 309SNP genotype in the BRCA1/2 groups (Fig 1A). Similar to the data presented for women without high expression of estrogen receptors [6], there was a trend for disease onset at a higher age in the G/G MDM2 309 group than in the T/T group in the non-BRCA mutation carriers (Fig. 1B and Table 3). Our data did not distinguish between high and low estrogen receptor expressers therefore we could not asses a correlation between high estrogen receptor expression and disease onset age in a similar manner to that performed by Bond and colleagues.


Effects of the single nucleotide polymorphism at MDM2 309 on breast cancer patients with/without BRCA1/2 mutations.

Nechushtan H, Hamburger T, Mendelson S, Kadouri L, Sharon N, Pikarsky E, Peretz T - BMC Cancer (2009)

Cancer onset age in the BRCA1/2 mutation carriers (A) and BRCA1/2 non carriers (B), according to their MDM2 SNP-309 subtypes. C and D prevalence of the SNP MDM309 genotypes in women above and bellow 51 years old – C total carrier population and D only BRCA1 mutation carriers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667534&req=5

Figure 1: Cancer onset age in the BRCA1/2 mutation carriers (A) and BRCA1/2 non carriers (B), according to their MDM2 SNP-309 subtypes. C and D prevalence of the SNP MDM309 genotypes in women above and bellow 51 years old – C total carrier population and D only BRCA1 mutation carriers.
Mentions: There was no significant difference between the prevalence of the different MDM2 SNP309 alleles between the BRCA1/2 patients (Table 2a) and the non carrier group (Table 2b). Disease onset age of breast cancer did seem to vary according to MDM2 309SNP genotype in the BRCA1/2 groups (Fig 1A). Similar to the data presented for women without high expression of estrogen receptors [6], there was a trend for disease onset at a higher age in the G/G MDM2 309 group than in the T/T group in the non-BRCA mutation carriers (Fig. 1B and Table 3). Our data did not distinguish between high and low estrogen receptor expressers therefore we could not asses a correlation between high estrogen receptor expression and disease onset age in a similar manner to that performed by Bond and colleagues.

Bottom Line: This result has been obtained in a relatively small subgroup and is of borderline statistical significance.Interestingly, in the BRCA1/2 mutation carriers, we found a survival advantage for patients harboring the SNP309 G/G genotype (p = 0.0086) but not for the 272 patients not harbouring this mutations.MDM2SNP309G/G main effect on BRCA1/2 positive mutation carriers is linked to its effect on patients survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel. hovavnech@hadassah.org.il

ABSTRACT

Background: A germ line single nucleotide polymorphism (SNP) in the first intron of the gene encoding MDM2 at position 309, an important modulator of p53, has been described. BRCA1/2 mutation have been associated with increased rates of breast cancers with mutated P53. It was shown that the presence of MDM2 309 SNP correlated with younger cancer onset age in individuals with a p53 mutations. The differential effects of this SNP were also linked to estrogen receptor activation. Here we report on our study of 453 Ashkenazi breast cancer patients of whom 180 were positive for the known Ashkenazi BRCA1/2 mutations

Methods: DNA from breast cancer patients was obtained for analysis of one of the three common BRCA1/2 mutations and MDM2 SNP309. Data regarding cancer onset and death ages was obtained from our database and Statistical analysis was performed using the SPSS statistical package (SPCC Inc., Chicago, IL), and JMP software (SAS Institute, Cary, NC).

Results: The percentage of MDM2 SNP309 in control and BRCA 1/2 population which is similar to that reported for other Jewish Ashkenazi populations at 52.2% for the heterozygotes and 25.0% for MDM2SNP309G/G and 22.8% for MDM2SNP309T/T.There was not a statistical significant difference in median age of disease onset in the different MDM2 SNP309 subgroups of the BRCA1/2 carriers. When we further divided the group into under and above 51 years old ( presumed menopause age) in the BRCA1 positive subset we found that there were less patients of the MDM2SNP309 G/G versus the MDM2SNP309 T/T in the over 51 patient group (p = 0.049). This result has been obtained in a relatively small subgroup and is of borderline statistical significance. Interestingly, in the BRCA1/2 mutation carriers, we found a survival advantage for patients harboring the SNP309 G/G genotype (p = 0.0086) but not for the 272 patients not harbouring this mutations.

Conclusion: MDM2SNP309G/G main effect on BRCA1/2 positive mutation carriers is linked to its effect on patients survival. Further research is needed in order to understand the reason for this difference.

Show MeSH
Related in: MedlinePlus