Epidemiological transition of colorectal cancer in developing countries: environmental factors, molecular pathways, and opportunities for prevention

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer and cancer-related mortality worldwide. The disease has been traditionally a major health problem in industrial countries, however the CRC rates are increasing in the developing countries that are undergoing economic growth. Several environmental risk factors, mainly changes in diet and life style, have been suggested to underlie the rise of CRC in these populations. Diet and lifestyle impinge on nuclear receptors, on the intestinal microbiota and on crucial molecular pathways that are implicated in intestinal carcinogenesis. In this respect, the epidemiological transition in several regions of the world offers a unique opportunity to better understand CRC carcinogenesis by studying the disease phenotypes and their environmental and molecular associations in different populations. The data from these studies may have important implications for the global prevention and treatment of CRC.

Keywords: Colorectal cancer; Developing countries; Diet; Environment; Gut microbiota; Nuclear receptors.

Figure 1

Comparison of the regional food consumption in the world, and the global spread of colorectal cancer, based on the data from Globocan 2008. A: Global cluster analysis based on 62 marker foods from 2002-2007 food supply data, reproduced with permission from World Health Organization GEMS/Food cluster diets analysis 2012 (details at http://www.who.int/foodsafety/chem/gems/en/index1.html). The analysis defined 17 diet clusters representing 179 countries for which food supply data were available. Here we highlight two major food clusters based on consumption of meat and fat, the major dietary colorectal cancer (CRC) risk factors. Clusters G7, 8, 10, 11 and 15 are in the high-meat-fat group, characterized by predominance of mammalian meat consumption (all > 108 g/d) and high total fat intake (all > 73 g/d). The low meat-fat group consists of clusters with lower mammalian meat consumption (all < 80 g/d) and lower overall fat intake (all < 51 g/d). Interestingly other high-risk dietary factors for CRC, such as overall high total food intake (> 2000 g/d) and total alcohol intake (> 200 g/d) are also associated with the meat-fat based diet group. The low-meat-fat group generally has lower total intake (except cluster G2) and lower total alcohol consumption (except cluster G16). The dietary profile in the low-meat-fat group is more heterogeneous, with variable intakes of other foods, such as fruit, vegetable, and cereal; B: CRC age-standardized incidence rates (ASR) per 100000 individuals per geographic region, as extracted from Globocan 2008[37]. Here we define regions with ASR of ≥ 24.2 as high-rate (red and orange), and regions with ASR < 24.2 (light green, dark green and yellow) as low-rate; C: Visual matching of the global regional CRC rates and dietary patterns, based on the groups defined above. Matching occurs when a region with high-meat-fat diet is high-rate for CRC, or when a region with low-meat-fat diet is low-rate for CRC. The regions where the CRC rates matched dietary pattern are in blue, those where it did not match in red (i.e., high-rate CRC regions with low-meat-fat diet or low-rate CRC regions with high-meat-fat diet).

Figure 2

Factors contributing to the uptrend of colorectal cancer incidence and mortality in developing countries.

Figure 3

Preventive strategies against colorectal cancer in developing countries.