MDM2 SNP309 G allele increases risk but the T allele is associated with earlier onset age of sporadic breast cancers in the Chinese population

Abstract

Sporadic breast cancer in women <40 years is uncommon in Caucasians, in contrast to a much earlier onset in Chinese Asians. However, the molecular determinants for this earlier onset are unclear. It has been reported that SNP309 in the promoter of MDM2, the negative regulator of p53, affects the onset age of cancers in females. Essentially, the G allele, rather than the T allele, has been suggested to accelerate the age of cancer onset. Hence, we examined if MDM2 and p53 polymorphisms would be determinants of the early onset phenomenon in Chinese women. Our results indicate that the MDM2 SNP309 G allele is more prevalent in the Chinese population compared with reported frequencies in Caucasians, and increases breast cancer risk of both sporadic cases and those with family history. However, it was the T/T genotype that was associated with earlier onset age of sporadic breast cancers in contrast to the G allele that was associated with the familial cases. Though p53 codon 72 single-nucleotide polymorphism (SNP) did not affect general cancer risk or age of onset, arginine homozygozity, in contrast to proline homozygozity, was found to decrease breast cancer risk in the later onset sporadic cases. Both SNP309 and codon 72 polymorphisms did not affect the stage of cancer. Together, the data suggest that though the MDM2 SNP309 G allele is a risk factor for breast cancer, it does not accelerate, but delays the onset of the sporadic disease in Chinese women, highlighting that differences in ethnicity and family history may influence the role of MDM2 SNP309 in cancer susceptibility.

Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with race: a meta-analysis

“…As a result, 16 case-control studies (12,986 breast cancer cases, 12,993 controls) were included in this meta-analysis [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Three studies had been performed in Chinese populations [8,16,19].…”

“…Concerning breast cancer, the discovery of the polymorphism has prompted investigators to conduct a variety of case-control studies, so as to examine whether MDM2 SNP309 is associated with breast cancer risk [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], age of onset [7,11,15,16,18,19] and prognosis [5,16,18,19].…”

“…Nearly 2 years since the above two contradictory metaanalyses, seven more case-control studies on the association between SNP309 and breast cancer have appeared [14][15][16][17][18][19][20]; this represents approximately 50% of the number of studies having been included in the previous metaanalyses. Therefore, the need for an updated meta-analysis of results has become evident.…”

An miR-502–Binding Site Single-Nucleotide Polymorphism in the 3′-Untranslated Region of the SET8 Gene Is Associated with Early Age of Breast Cancer Onset

“…Epidemiologic studies have begun to systematically interrogate single-nucleotide polymorphisms in critical genes to unravel specific genotypes that contribute to an increased risk for cancer development and/or a specific pattern of cancer development such as early age of onset (7). The single-nucleotide polymorphism at codon 72 of the TP53 gene resulting in two different amino acids (Pro or Arg) is one of the most extensively studied single-nucleotide polymorphisms that have been shown to influence cancer incidence in a number of cancer types, including cervical cancer (8).…”

The Role of p16 and MDM2 Gene Polymorphisms in Prolactinoma: MDM2 Gene Polymorphisms May Be Associated with Tumor Shrinkage

“…Recent evidence indicates cellular stress factors that could lead to genotoxic injuries such as cytokines, growth factors, hypoxia, and metabolic alterations. These may be effective at the initial phase of p53 response and may cause differences in functionality of polymorphisms (43).…”