Research Highlights

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  • Genetics

Published online: 20 May 2009 | doi:10.1038/nchina.2009.113

Oncology: Stress factors

Felix Cheung

Introduction

© (2009) istockphoto.com/Zhang Bo

The tumour suppressor p53 is a master sensor of stress. It triggers a wide range of cellular functions, including cell-cycle arrest, DNA repair and apoptosis, in response to environmental stresses. The negative regulator Mdm2 regulates the level of p53 under normal conditions. In humans, p53 codon 72 and MDM2 SNP309 are two genetic variations (single-nucleotide polymorphisms (SNPs)) that influence the activities of p53 and Mdm2. Bing Su at the Chinese Academy of Sciences in Kunming and co-workers¹ have evidence to show that these SNPs naturally evolved in East Asians in response to temperature changes and ultraviolet radiation.

Previous studies have shown that p53 codon 72 and MDM2 SNP309 are more common in northern Europeans than in Africans or African-Americans. Su and co-workers hypothesized that the frequency of these SNPs is not only dependent on ethnicity, but also on environmental stresses.

The researchers examined a cohort of 4,029 Chinese individuals living in vastly different latitudes across Eastern Asia. They found the frequency of p53 codon 72 and MDM2 SNP309 to be latitude dependent. In particular, p53 codon 72 was more common in people living in latitudes with cold winter temperatures, whereas MDM2 SNP309 was more common in people living in latitudes with low ultraviolet radiation.

The precise regulation of activities of both p53 and Mdm2 is vital for embryonic development and homeostasis. The researchers believe p53 codon 72 and MDM2 SNP309 might provide a selective advantage in the adaptation of environmental stresses — for example, by increasing the success rate of embryonic implantation in colder climates.

The authors of this work are from:
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology and Kunming Primate Research Centre, Chinese Academy of Sciences, Kunming, China; Human Genetics Centre, Yunnan University, Kunming, China; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China; Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA; Qujing Normal College, Qujing, China; Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.

Reference

1. Shi, H. et al. Winter temperature and UV are tightly linked to genetic changes in the p53 tumor suppressor pathway in Eastern Asia. Am. J. Hum. Genet. 84, 534–541 (2009). | Article | PubMed |