MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer.
MDM2 promoter SNP55 (rs2870820) affects risk of colon cancer but not breast-, lung-, or prostate cancer.
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DOI：
10.1038/srep33153
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发表时间：
2016-09-14
影响因子：
4.6
通讯作者：
Knappskog S
中科院分区：
文献类型：
--
作者：
Helwa R;Gansmo LB;Romundstad P;Hveem K;Vatten L;Ryan BM;Harris CC;Lønning PE;Knappskog S
两个功能性snp （SNP285G > C； rs117039649和SNP309T > G; rs2279744）先前已被报道可调节Sp1转录因子与原癌基因MDM2启动子的结合，并影响癌症风险。最近，第三个SNP （SNP55C > T; rs2870820）也被报道影响Sp1结合和MDM2转录。在这项基于大量人群的病例对照研究中，我们对10779名高加索人的MDM2 SNP55进行了基因分型，之前对SNP309和SNP285进行了基因分型，包括结肠癌（n = 1524）、肺癌（n = 1323）、乳腺癌（n = 1709）和前列腺癌（n = 2488）病例，以及3735名非癌症对照者，以及299名健康的非洲裔美国人。应用优势模型，我们发现携带SNP55TT/CT基因型的个体患结肠癌的风险高于携带SNP55CC基因型的个体（OR = 1.15; 95% CI = 1.01-1.30）。发现左侧结肠癌的风险最高（OR = 1.21; 95% CI = 1.00-1.45）和女性（OR = 1.32; 95% CI = 1.01-1.74）。评估联合基因型，我们发现携带SNP55TT或CT和SNP309TG基因型的个体患结肠癌的风险最高（or = 1.21; 95% CI = 1.00-1.46）。支持风险评估的结论，我们发现携带SNP55TT/CT基因型的结肠癌患者比携带SNP55CC的患者诊断年龄更小（p = 0.053），特别是携带SNP309TG/TT基因型的患者（p = 0.009）。
Two functional SNPs (SNP285G > C; rs117039649 and SNP309T > G; rs2279744) have previously been reported to modulate Sp1 transcription factor binding to the promoter of the proto-oncogene MDM2, and to influence cancer risk. Recently, a third SNP (SNP55C > T; rs2870820) was also reported to affect Sp1 binding and MDM2 transcription. In this large population based case-control study, we genotyped MDM2 SNP55 in 10,779 Caucasian individuals, previously genotyped for SNP309 and SNP285, including cases of colon (n = 1,524), lung (n = 1,323), breast (n = 1,709) and prostate cancer (n = 2,488) and 3,735 non-cancer controls, as well as 299 healthy African-Americans. Applying the dominant model, we found an elevated risk of colon cancer among individuals harbouring SNP55TT/CT genotypes compared to the SNP55CC genotype (OR = 1.15; 95% CI = 1.01–1.30). The risk was found to be highest for left-sided colon cancer (OR = 1.21; 95% CI = 1.00–1.45) and among females (OR = 1.32; 95% CI = 1.01–1.74). Assessing combined genotypes, we found the highest risk of colon cancer among individuals harbouring the SNP55TT or CT together with the SNP309TG genotype (OR = 1.21; 95% CI = 1.00–1.46). Supporting the conclusions from the risk estimates, we found colon cancer cases carrying the SNP55TT/CT genotypes to be diagnosed at younger age as compared to SNP55CC (p = 0.053), in particular among patients carrying the SNP309TG/TT genotypes (p = 0.009).
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影响因子：
3.7
作者：
Knappskog S;Gansmo LB;Romundstad P;Bjørnslett M;Trovik J;Sommerfelt-Pettersen J;Løkkevik E;Norwegian Breast Cancer Group trial NBCG VI;Tollenaar RA;Seynaeve C;Devilee P;Salvesen HB;Dørum A;Hveem K;Vatten L;Lønning PE
通讯作者：
Lønning PE
影响因子：
7.7
作者：
Naess, Oyvind;Sogaard, Anne Johanne;Aamodt, Geir
通讯作者：
Aamodt, Geir
影响因子：
64.5
作者：
FISHEL, R;LESCOE, MK;KOLODNER, R
通讯作者：
KOLODNER, R
影响因子：
3.8
作者：
Economopoulos, Konstantinos P.;Sergentanis, Theodoros N.
通讯作者：
Sergentanis, Theodoros N.
影响因子：
64.5
作者：
Bond, GL;Hu, WW;Levine, AJ
通讯作者：
Levine, AJ