title: 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.
authors.affiliation: Laboratory of Molecular Carcinogenesis, Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: San San
authors.initials: SS
authors.lastname: Lum
authors.forename: Hui Wan
authors.initials: HW
authors.lastname: Chua
authors.forename: Huihua
authors.initials: H
authors.lastname: Li
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Li
authors.forename: Nanyan
authors.initials: N
authors.lastname: Rao
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Shao
authors.forename: Kanaga
authors.initials: K
authors.lastname: Sabapathy
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002681:China; D003062:Codon; D005260:Female; D020022:Genetic Predisposition to Disease; D006147:Guanine; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics; D012307:Risk Factors
chemical_list: D003062:Codon; D011960:Receptors, Estrogen; D006147:Guanine; D051736:Proto-Oncogene Proteins c-mdm2