Open AccessMDM4 SNP34091 (rs4245739) and its effect on breast‐, colon‐, lung‐, and prostate cancer risk
Author(s) -
Gansmo Liv B.,
Romundstad Pål,
Birkeland Einar,
Hveem Kristian,
Vatten Lars,
Knappskog Stian,
Lønning Per Eystein
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.555
Subject(s) - breast cancer , prostate cancer , medicine , oncology , case control study , mdm2 , colorectal cancer , prostate , lung cancer , genotype , population , cancer , biology , genetics , gene , environmental health
The MDM4 protein plays an important part in the negative regulation of the tumor suppressor p53 through its interaction with MDM2. In line with this, MDM4 amplification has been observed in several tumor forms. A polymorphism (rs4245739 A>C; SNP34091) in the MDM4 3′ untranslated region has been reported to create a target site for hsa‐miR‐191, resulting in decreased MDM4 mRNA levels. In this population‐based case–control study, we examined the potential association between MDM4 SNP34091, alone and in combination with the MDM2 SNP309T>G (rs2279744), and the risk of breast‐, colon‐, lung‐, and prostate cancer in Norway. SNP34091 was genotyped in 7,079 cancer patients as well as in 3,747 gender‐ and age‐matched healthy controls. MDM4 SNP34091C was not associated with risk for any of the tumor forms examined, except for a marginally significant association with reduced risk for breast cancer in a recessive model (OR = 0.77: 95% CI = 0.59–0.99). Stratifying according to MDM2 SNP309 status, we observed a reduced risk for breast cancer related to MDM4 SNP34091CC among individuals harboring the MDM2 SNP309GG genotype (OR = 0.41; 95% CI = 0.21–0.82). We conclude, MDM4 SNP34091 status to be associated with reduced risk of breast cancer, in particular in individuals carrying the MDM2 SNP309GG genotype, but not to be associated with either lung‐, colon‐ or prostate cancer.