PERSPECTIVES foods, sugars, saturated fat and meats. These adaptations are due, in part, to the mecha- nization and modernization of processes ranging from transportation to household chores. Additionally there is increasing avail- ability and demand for cheaper food options, which tend to be high in both fat and sodium and low in fibre. Such adaptations are often referred to as ‘Westernization’ — the umbrella term that encompasses these behaviours, which are common in North America and parts of Europe. Most of the research into cancer has been done on people living in North America and Europe, representing only a fraction of the global population and their dietary patterns and lifestyle factors. The wide variety of diet, lifestyle and environmental exposures, as well as genetic variation between populations in developing countries, can add valuable infor- mation to our knowledge of the factors that contribute to the development of cancer. The international portfolio of cancer studies there- fore needs to be expanded to developing countries. These types of studies would not only serve the needs of people in developing countries, but also progress our overall knowl- edge of cancer aetiology. There are, however, many logistical issues that need to be addressed when performing epidemiological studies in developing nations. These include defining research priorities by taking into con- sideration past scientific discoveries so that efforts are not unnecessarily repeated and lim- ited resources are preserved. Furthermore, key infrastructure requirements need to be con- sidered, as well as strengthening the epidemio- logical research capabilities of institutions in developing countries. Regional variation in cancer incidence Incidence of cancer varies dramatically between geographic regions (FIG. 2); as some cancers are more common in people in the developed world (for example, breast and prostate), others occur more frequently in people who live in developing countries (for example, cervical and stomach). Cancers of the lung have high incidence in both developed countries and areas undergoing economic development such as China 1 . Although these regional differences might be explained by genetic differences among pop- ulations, variations in lifestyles, environmen- tal exposures and medical practices such as screening are also likely to be important determinants of cancer risk. This assumption is reinforced by migration patterns that show that incidence of cancer among migrants changes to more closely reflect the rates in the adoptive country. This has been observed 125. Love, R. R. et al. Her-2/neu overexpression and response to oophorectomy plus tamoxifen adjuvant therapy in estrogen receptor-positive premenopausal women with operable breast cancer. J. Clin. Oncol. 21, 453–457 (2003). 126. Santen, R. J. et al. Estrogen production via the aromatase enzyme in breast carcinoma: which cell type is responsible? J. Steroid Biochem. Mol. Biol. 61, 267–271 (1997). 127. Smithers, D. W. An attack on cytologism. Lancet 1, 493–499 (1962). 128. Watson, J. V. What does “response” in cancer chemotherapy really mean? Br. Med. J. 283, 34–37 (1981). 129. Onuffer, J. J. & Horuk, R. Chemokines, chemokine receptors and small-molecule antagonists: recent developments. Trends Pharmacol. Sci. 23, 459–467 (2002). 130. Hatse, S., Princen, K., Bridger, G., De Clercq, E. & Schols, D. Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. FEBS Lett. 527, 255–262 (2002). 131. Zhang, L., Kharbanda, S., Hanfelt, J. & Kern, F. G. Both autocrine and paracrine effects of transfected acidic fibroblast growth factor are involved in the estrogen- independent and antiestrogen-resistant growth of MCF-7 breast cancer cells. Cancer Res. 58, 352–361 (1998). 132. Bogdanos, J. et al. Endocrine/paracrine/autocrine survival factor activity of bone microenvironment participates in the development of androgen ablation and chemotherapy refractoriness of prostate cancer metastasis in skeleton. Endocr. Rel. Cancer 10, 279–289 (2003). 133. Kouniavsky, G. et al. Stromal extracellular matrix reduces chemotherapy-induced apoptosis in colon cancer cell lines. Clin. Exp. Metastasis 19, 55–60 (2002). 134. Fortney, J. E., Zhao, W., Wenger, S. L. & Gibson L. F. Bone marrow stromal cells regulate caspase 3 activity in leukemic cells during chemotherapy. Leuk. Res. 25, 901–907 (2001). 135. Pietras, K. et al. Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res. 62, 5476–5484 (2002). 136. Zondor, S. D. & Medina, P. J. Bevacizumab: an angiogenesis inhibitor with efficacy in colorectal and other malignancies. Ann. Pharmacother. 38, 1258–1264 (2004). 137. Liang, Z. et al. Inhibition of breast cancer metastasis by selective synthetic peptides against CXCR4. Cancer Res. 64, 4302–4308 (2004). 138. Tamamura, H. et al. T140 analogs as CXCR4 antagonists identified as antimetastatic agents in the treatment of breast cancer. FEBS Lett. 550, 79–83 (2003). 139. Mihara, M. et al. p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 11, 577–590 (2003). 140. Erster, S., Mihara, M., Kim, R. H., Petrenko, O. & Mol, U. M. In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol. Cell. Biol. 24, 6728–6741 (2004). Acknowledgements Thanks are due to B.S. Mann of the Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA, and to J.C. Chim from the Division of Haematology/Oncology, Queen Mary Hospital, Hong Kong, for constructive comments on the manuscript. Competing interests statement The author declares no competing financial interests. Online links DATABASES The following terms in this article are linked online to: Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene AKT | β-catenin | cathepsin G | CXCL12 | CXCR4 | DPPIV | E-cadherin | ERBB2 | FAK | G-CSF | p53 | VCAM1 | VHL National Cancer Institute: http://cancer.gov/ breast cancer Access to this interactive links box is free online. NATURE REVIEWS | CANCER VOLUME 4 | NOVEMBER 2004 | 909 Opportunities for cancer epidemiology in developing countries Tanuja Rastogi, Allan Hildesheim and Rashmi Sinha SCIENCE AND SOCIETY Abstract | Most cancer epidemiology studies involve people living in North America and Europe, which represent only a fraction of the global population. The wide variety of dietary, lifestyle and environmental exposures, as well as the genetic variation among people in developing countries can provide valuable new information on factors that contribute to cancer or that protect against it. What are the challenges and advantages to performing large epidemiological studies in developing nations? The incidence of cancer and other chronic diseases is increasing in developing countries owing to increased life expectancy and changes in risk factors that are concomitant with economic development. The dramatic improvements in life expectancy that are observed in middle-income countries can be attributed to better public health practices such as immunization and improved nutrition. This has reduced infant and child mortalities from infectious diseases and malnutrition. By contrast, according to the World Health Organization, mortality from cancer is expected to increase considerably in developing countries including Asia, Africa and Latin America (FIG. 1). Although cancer incidence rates are still substantially lower in developing countries than in developed coun- tries, the burden of cancer and other chronic diseases pose an important threat to already overwhelmed health-care systems. Changes in lifestyle and diet that occur with economic development typically include unhealthy practices such as sedentary behaviour, smoking, increased total energy intake and consumption of highly refined