Carcinogenesis Advance Access published online on February 14, 2008
Carcinogenesis, 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 Division of Cellular & 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 Dept 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
Correspondence to: Kanaga Sabapathy, Ph.D., Laboratory of Molecular Carcinogenesis, Division of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 11, Hospital Drive, Singapore 169610, Tel.: +65 6436 8349, Fax: +65 6226 5694, email: cmrksb{at}nccs.com.sg
Sporadic breast cancer in women under 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 SNP309G allele is more prevalent in the Chinese population compared to 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 associated with the familial cases. Though p53 codon 72 SNP did not affect general cancer risk or age of onset, Arg homozygozity, in contrast to Pro 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 suggests that though the MDM2 SNP309G 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.
Key Words: MDM2 SNP • p53 codon 72 SNP • early-onset breast cancer
Received September 3, 2007; revised January 17, 2008; accepted January 18, 2008.