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

S. Knappskog; L.B. Gansmo; K. Dibirova; A. Metspalu; C. Cybulski; P. Peterlongo; L. Aaltonen; L. Vatten; P. Romundstad; K. Hveem; P. Devilee; G.D. Evans; D. Lin; G.V. Van Camp; V.G. Manolopoulos; A. Osorio; L. Milani; T. Ozcelik; P. Zalloua; F. Mouzaya; E. Bliznetz; E. Balanovska; E. Pocheshkova; V. Kucinskas; L. Atramentova; P. Nymadawa; K. Titov; M. Lavryashina; Y. Yusupov; N. Bogdanova; S. Koshel; J. Zamora; D.C. Wedge; D. Charlesworth; T. Dörk; O. Balanovsky; P.E. Lønning

doi:10.18632/oncotarget.1910

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

S. Knappskog, L.B. Gansmo, K. Dibirova, A. Metspalu, C. Cybulski, P. Peterlongo, L. Aaltonen, L. Vatten, P. Romundstad, K. Hveem, P. Devilee, G.D. Evans, D. Lin, G.V. Van Camp, V.G. Manolopoulos, A. Osorio, L. Milani, T. Ozcelik, P. Zalloua, F. MouzayaE. Bliznetz, E. Balanovska, E. Pocheshkova, V. Kucinskas, L. Atramentova, P. Nymadawa, K. Titov, M. Lavryashina, Y. Yusupov, N. Bogdanova, S. Koshel, J. Zamora, D.C. Wedge, D. Charlesworth, T. Dörk, O. Balanovsky, P.E. Lønning

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	8223-8234
Number of pages	12
Journal	Oncotarget
Volume	5
Issue number	18
DOIs	https://doi.org/10.18632/oncotarget.1910
Publication status	Published - Sept 2014

Keywords

MDM2
Polymorphism
Promoter
SNP285
SNP309

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.1910

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Knappskog, S., Gansmo, L. B., Dibirova, K., Metspalu, A., Cybulski, C., Peterlongo, P., Aaltonen, L., Vatten, L., Romundstad, P., Hveem, K., Devilee, P., Evans, G. D., Lin, D., Van Camp, G. V., Manolopoulos, V. G., Osorio, A., Milani, L., Ozcelik, T., Zalloua, P., ... Lønning, P. E. (2014). Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649). Oncotarget, 5(18), 8223-8234. https://doi.org/10.18632/oncotarget.1910

@article{48afcaf2aabc44ab893b7667310593b7,

title = "Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)",

abstract = "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.",

keywords = "MDM2, Polymorphism, Promoter, SNP285, SNP309",

author = "S. Knappskog and L.B. Gansmo and K. Dibirova and A. Metspalu and C. Cybulski and P. Peterlongo and L. Aaltonen and L. Vatten and P. Romundstad and K. Hveem and P. Devilee and G.D. Evans and D. Lin and {Van Camp}, G.V. and V.G. Manolopoulos and A. Osorio and L. Milani and T. Ozcelik and P. Zalloua and F. Mouzaya and E. Bliznetz and E. Balanovska and E. Pocheshkova and V. Kucinskas and L. Atramentova and P. Nymadawa and K. Titov and M. Lavryashina and Y. Yusupov and N. Bogdanova and S. Koshel and J. Zamora and D.C. Wedge and D. Charlesworth and T. D{\"o}rk and O. Balanovsky and P.E. L{\o}nning",

year = "2014",

month = sep,

doi = "10.18632/oncotarget.1910",

language = "English",

volume = "5",

pages = "8223--8234",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals LLC",

number = "18",

}

Knappskog, S, Gansmo, LB, Dibirova, K, Metspalu, A, Cybulski, C, Peterlongo, P, Aaltonen, L, Vatten, L, Romundstad, P, Hveem, K, Devilee, P, Evans, GD, Lin, D, Van Camp, GV, Manolopoulos, VG, Osorio, A, Milani, L, Ozcelik, T, Zalloua, P, Mouzaya, F, Bliznetz, E, Balanovska, E, Pocheshkova, E, Kucinskas, V, Atramentova, L, Nymadawa, P, Titov, K, Lavryashina, M, Yusupov, Y, Bogdanova, N, Koshel, S, Zamora, J, Wedge, DC, Charlesworth, D, Dörk, T, Balanovsky, O & Lønning, PE 2014, 'Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)', Oncotarget, vol. 5, no. 18, pp. 8223-8234. https://doi.org/10.18632/oncotarget.1910

TY - JOUR

T1 - Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)

AU - Knappskog, S.

AU - Gansmo, L.B.

AU - Dibirova, K.

AU - Metspalu, A.

AU - Cybulski, C.

AU - Peterlongo, P.

AU - Aaltonen, L.

AU - Vatten, L.

AU - Romundstad, P.

AU - Hveem, K.

AU - Devilee, P.

AU - Evans, G.D.

AU - Lin, D.

AU - Van Camp, G.V.

AU - Manolopoulos, V.G.

AU - Osorio, A.

AU - Milani, L.

AU - Ozcelik, T.

AU - Zalloua, P.

AU - Mouzaya, F.

AU - Bliznetz, E.

AU - Balanovska, E.

AU - Pocheshkova, E.

AU - Kucinskas, V.

AU - Atramentova, L.

AU - Nymadawa, P.

AU - Titov, K.

AU - Lavryashina, M.

AU - Yusupov, Y.

AU - Bogdanova, N.

AU - Koshel, S.

AU - Zamora, J.

AU - Wedge, D.C.

AU - Charlesworth, D.

AU - Dörk, T.

AU - Balanovsky, O.

AU - Lønning, P.E.

PY - 2014/9

Y1 - 2014/9

N2 - 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.

AB - 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.

KW - MDM2

KW - Polymorphism

KW - Promoter

KW - SNP285

KW - SNP309

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84907998640&partnerID=MN8TOARS

U2 - 10.18632/oncotarget.1910

DO - 10.18632/oncotarget.1910

M3 - Article

C2 - 25327560

SN - 1949-2553

VL - 5

SP - 8223

EP - 8234

JO - Oncotarget

JF - Oncotarget

IS - 18

ER -

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

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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