MDM4 SNP34091 (rs4245739) and its effect on breast‐, colon‐, lung‐, and prostate cancer risk

Abstract

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.

The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancer

“…In the same study, no association between SNP34091 status and risk for cancer of the lung, colon, or prostate was observed [17]. Our findings in the present study are, however, in line with previous studies reporting SNP34091C to be associated with increased risk for triple-negative breast cancer [23, 24], a subclass of breast cancers sharing some mutational features with HGSOC [35].…”

“…These were the female fraction of a sample set of 3747 healthy individuals, previously genotyped [17], and they were all obtained from the population-based Cohort of Norway (CONOR) study [30]. …”

The Role of MDM4 SNP34091 A>C Polymorphism in Cancer: A Meta-Analysis on 19,328 Patients and 51,058 Controls

“…MDM4 is a transcriptional regulator that binds to and inhibits p53 (6). Gansmo et al (16) found that the MDM4 SNP34091 (rs4245739) polymorphism was not associated with risks for colon, lung and prostate cancer. However, Fan et al (17) found a significantly decreased non-Hodgkin lymphoma risk among carriers of the MDM4 rs4245739 C allele in Chinese.…”

“…After removal of duplicates, 97 potentially relevant studies were retrieved. Based on the inclusion and exclusion criteria, 90 studies were excluded and 7 were included in this meta-analysis (14)(15)(16)(17)(18)(19)(20). Three case-control studies involved 2 different geographical regions (15,18,19), so they were considered as separate studies.…”

HDM2 and HDMX Proteins in Human Cancer

“…Jeden z prvých prístupov aktivujúcich p53 dráhu skrz inhibíciu proteín-proteí-ším študovaným polymorfizmom HDMX je SNP34091 A > C, avšak jednoznačné spojenie s výskytom v určitých typoch rakoviny zatiaľ nebolo preukázané [76,77].…”