Murine Double Minute Clone 2 309T/G and 285G/C Promoter Single Nucleotide Polymorphism as a Risk Factor for Breast Cancer: A Polish Experience

Piotrowski, Piotr; Lianeri, Margarita; Rubiś, Błażej; Knuła, Hanna; Rybczyńska, Maria; Grodecka-Gazdecka, Sylwia; Jagodzińśki, Paweł P.

doi:10.5301/jbm.2012.9140

Cited by 11 publications

(8 citation statements)

References 44 publications

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“…16,17 This haplotype is widespread across Caucasian populations, but appear to be absent among ethnic Asians and Africans. 24 Previously, we and others have reported that the SNP285C variant may be associated with reduced risk for breast, 16,20 ovarian 16 and endometrial 19 cancer, and others reported a reduced age at cancer diagnosis related to the SNP285G allele among individuals with the Li-Fraumeni syndrome. 41 In contrast, previous reports have indicated SNP285C not to be associated with the risk of either lung 21 or prostate cancer.…”

Section: Discussionmentioning

confidence: 96%

“…16,17 The C-allele of SNP285 seems to antagonize the effect of SNP309G by reducing the binding affinity of the Sp1 transcription factor to the MDM2 promoter. 16,18 Moreover, the SNP285C/309G haplotype has been associated with a reduced risk for ovarian, breast and endometrial cancer 16,19,20 but was found not to be associated with risk for cancer of the prostate or lung. 19,21 Finally, the SNP285C has also been found to reduce the risk of BRCA1 related ovarian cancer in individuals carrying the SNP309G allele.…”

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confidence: 99%

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Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon

Gansmo

Knappskog

Romundstad

et al. 2014

Intl Journal of Cancer

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MDM2 is a key regulator of the p53 tumor suppressor protein and is overexpressed in many human cancers. Two single nucleotide polymorphisms (SNPs) located in the MDM2 intronic promoter (P2) have been found to exert biological function. The Gallele of SNP309T>G; rs2279744 increases MDM2 transcription and has been linked to increased cancer risk. In contrast, the less frequent SNP285G>C; rs117039649, which is in complete linkage disequilibrium with SNP309 (generating a SNP285C/ 309G variant haplotype), has been related to reduced MDM2 transcription and to reduced risk of breast, endometrial and ovarian cancer. In this large population-based case-control study, we genotyped SNP309 and SNP285 in 10,830 individuals, including cases with cancer of the breast (n51,717), colon (n51,532), lung (n51,331) and prostate (n52,501), as well as 3,749 non-cancer controls. We found a slightly reduced risk for lung cancer among individuals harboring the SNP309TG/GG genotypes compared to the SNP309TT genotype (OR5 0.86; CI 5 0.67-0.98), but this association was restricted to women (OR 5 0.77; CI 5 0.63-0.95) and was not present among men (OR 5 0.91; CI 5 0.77-1.08). Consistent with previous findings, we found a reduced risk for breast cancer among individuals carrying the SNP285GC/309GG genotype versus the SNP285GG/ 309GG genotype (OR 5 0.55; CI 5 0.33-0.93). In conclusion, our data support the hypothesis that the effects of both SNP285 and SNP309 status are tissue dependent.

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Section: Discussionmentioning

confidence: 96%

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confidence: 99%

Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon

Gansmo

Knappskog

Romundstad

et al. 2014

Intl Journal of Cancer

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“…Paulin and co-workers found SNP285C in 4.4% of healthy Scottish individuals [19], while Piotrowski and colleagues found the variant C-allele in 10.2 % of healthy Polish individuals [20]. Further, Ryan and colleagues found 6% of Americans of Caucasian ancestry to harbor SNP285C [21], while Renaux-Petel and co-workers found this variant among 5.2% of French individuals diagnosed with germline TP53 mutations [Li-Fraumeni patients; 22].…”

Section: Discussionmentioning

confidence: 99%

Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)

et al. 2014

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The MDM2 promoter SNP285C is located on the SNP309G allele. While SNP309G enhances Sp1 transcription factor binding and MDM2 transcription, SNP285C antagonizes Sp1 binding and reduces the risk of breast-, ovary- and endometrial cancer. Assessing SNP285 and 309 genotypes across 25 different ethnic populations (>10.000 individuals), the incidence of SNP285C was 6-8% across European populations except for Finns (1.2%) and Saami (0.3%). The incidence decreased towards the Middle-East and Eastern Russia, and SNP285C was absent among Han Chinese, Mongolians and African Americans. Interhaplotype variation analyses estimated SNP285C to have originated about 14,700 years ago (95% CI: 8,300 – 33,300). Both this estimate and the geographical distribution suggest SNP285C to have arisen after the separation between Caucasians and modern day East Asians (17,000 - 40,000 years ago). We observed a strong inverse correlation (r = -0.805; p < 0.001) between the percentage of SNP309G alleles harboring SNP285C and the MAF for SNP309G itself across different populations suggesting selection and environmental adaptation with respect to MDM2 expression in recent human evolution. In conclusion, we found SNP285C to be a pan-Caucasian variant. Ethnic variation regarding distribution of SNP285C needs to be taken into account when assessing the impact of MDM2 SNPs on cancer risk.

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“…SNP285 is in complete linkage disequilibrium (LD) with SNP309; thus forming a distinct SNP285C/309G haplotype [ 18 , 19 ]. The SNP285C allele diminish Sp1 binding to the MDM2 promoter, and has been found to be associated with reduced risk for breast, ovarian and endometrial cancer [ 18 , 20 – 22 ], but was not associated with prostate or lung cancer risk [ 20 , 21 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Associations between the MDM2 promoter P1 polymorphism del1518 (rs3730485) and incidence of cancer of the breast, lung, colon and prostate

et al. 2016

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The MDM2 promoter region contains several polymorphisms, some of which have been associated with MDM2 expression, cancer risk and age at cancer onset. del1518 (rs3730485) is an indel polymorphism residing in the MDM2 promoter P1 and is in almost complete linkage disequilibrium with the MDM2 promoter P2 polymorphism SNP309T>G (rs2279744). Cancer risk assessments of del1518 have previously been conducted in relatively small Chinese populations only. In this study we assessed the genotype distribution of del1518 among healthy Caucasians, African Americans and Chinese, and we estimated the Odds Ratios (OR) for incident cancer of the breast, colon, lung and prostate (n=7,081) as compared to controls (n=3,749) in a large Caucasian (Norwegian) cohort.We found the genotypes of the del1518 to vary significantly between healthy Caucasians, African-Americans and Chinese (p< 1×10−5). Further, we found a positive association of the del1518 del-allele with risk of colon cancer (dominant model: OR = 1.15; 95 % CI = 1.01 – 1.31). Stratifying according to SNP309 status, this association remained among carriers of the SNP309TG genotype (OR = 1.21; 95 % CI = 1.01 – 1.46), but with no clear association among carriers of the SNP309TT genotype. In conclusion, our findings suggest del1518 to be associated with increased risk of colon cancer.

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Murine Double Minute Clone 2 309T/G and 285G/C Promoter Single Nucleotide Polymorphism as a Risk Factor for Breast Cancer: A Polish Experience

Abstract: In a sample of the Polish population, we observed that the MDM2 285C gene variant may be a significant protective factor against breast cancer.

Cited by 11 publications

References 44 publications

Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon

Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon

Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)

Associations between the MDM2 promoter P1 polymorphism del1518 (rs3730485) and incidence of cancer of the breast, lung, colon and prostate

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