Carcinogenesis Advance Access originally published online on February 14, 2008
Carcinogenesis 2008 29(4):754-761; doi:10.1093/carcin/bgn024
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MDM2 SNP309 G allele increases risk but the T allele is associated with earlier onset age of sporadic breast cancers in the Chinese population
1 Laboratory of Molecular Carcinogenesis, Division of Cellular and Molecular Research
2 Division of Clinical Trials and Epidemiological Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore
3 Department of Breast Surgery, Cancer Hospital/Cancer Institute, Fudan University, Shanghai 200032, People’s Republic of China
4 Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore
5 Present address: Department of Oncology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, People’s Republic of China
* To whom correspondence should be addressed. Tel: +65 6436 8349; Fax: +65 6226 5694; Email: cmrksb{at}nccs.com.sg
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.
Abbreviations: Arg, arginine; ER, estrogen receptor; OR, odds ratio; PCR, polymerase chain reaction; Pro, proline; SNP, single-nucleotide polymorphism
Received September 3, 2007; revised January 17, 2008; accepted January 18, 2008.
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