Abstract SY14-01: Preventable exposures associated with human cancer.
Authors: Christopher Paul Wild
Journal: Cancer Research (2013)

Abstract The worldwide burden of cancer and other non-communicable diseases (NCDs) is increasing. In 2005, NCDs were estimated to have caused more than 60% (35 million) of all deaths worldwide. For cancer an estimated 7.6 million deaths occurred in 2008 (around 20% of all NCD deaths). Without prevention or control the total cancer deaths is projected to rise to 13.1 million by 2030 whilst incidence will rise from 12.7 million in 2008 to 21.3 in 2030 based on demographic changes alone. The greatest percent increases will be in countries falling within the low and medium Human Development Index (HDI) categories. This phenomenon is mainly a consequence of the epidemiologic transition, i.e., a shift from infectious diseases to NCDs. Wider adoption of specific aspects of westernized lifestyles would translate to still greater increases in certain cancer types. In many countries the burden of cancer and other NCDs will therefore add to communicable diseases and malnutrition to impose a “double burden” on the poorest. These trends represent major challenges to health, poverty, sustainable development and equality. One consequence, especially in the lower HDI countries, is the implausibility of treating our way out of the cancer epidemic. Large variations in the type and number of cancers are observed in different regions of the world. Within high- and very high-HDI countries, prostate and breast cancers are the most common in males and females respectively, with lung and colorectal cancers ranking next in both sexes. Within low-HDI countries lung and breast cancers remain among the most common, but cancers of the cervix, stomach, liver, and Kaposi sarcoma are also among the leading types – all of which are cancers with infection-related aetiology. Medium-HDI countries are intermediate with respect to their patterns of cancer burden, reflecting an on-going transition from infection-related cancers to those most associated with a westernized lifestyle. The three most common types of cancer in medium-HDI countries are lung, stomach and liver cancers in males, and breast, cervix and lung cancer in females. In face of these increases in burden and variations in types of cancer, both primary and secondary cancer prevention offer many opportunities through implementing existing knowledge about environmental and lifestyle risk factors and using the natural history of the disease to establish screening and early detection. Reducing tobacco consumption through primary prevention has the capacity to contribute globally to the largest number of cancer deaths avoided; implementation of the international treaty of the WHO Framework Convention on Tobacco Control is vital. Effective tobacco control efforts have resulted in substantial declines in tobacco-related cancer deaths in the USA and several European countries demonstrating the effectiveness of a range of control methods. In relation to diet there are a number of clear potentially modifiable risk factors. Obesity is associated with an increased risk of breast, colorectal, endometrium, kidney, oesophageal and pancreatic cancers. Physical inactivity is also associated with breast, colorectal and endometrium cancer. Much less is known about specific nutrients or dietary components, although alcohol is associated with increased risks of liver, aero-digestive tract, breast and colorectal cancers; the consumption of red and processed meats as well as a diet low in fibre has also been associated with colorectal cancer. Recent estimates reported about 2 million cancer cases per year (16% of the global cancer burden) attributable to chronic infections, principally human papillomavirus (HPV); hepatitis B virus (HBV) and hepatitis C virus (HCV); and Helicobacter pylori (H. pylori). The contribution is substantially larger in low-resource countries (that include low- and medium-HDI countries) (26%) than in high-resource countries (8%) making the prevention or eradication of these infections a powerful tool to overcome inequalities in cancer incidence between poor and rich populations. Priorities include vaccination against HBV and HPV and avoidance of HCV transmission. Environmental causes of cancer, encompassing environmental contaminants or pollutants (e.g. radon, indoor and outdoor air pollution), naturally occurring toxins (e.g. aflatoxins, arsenic), occupationally-related exposures (e.g. asbestos) and radiation (X-rays and gamma radiation, as well as sunlight and UV tanning devices) can make substantial contributions to specific cancers or cancer clusters on a smaller scale. These exposures can also be amenable to low-cost modification by regulation, thus reducing the burden of some very lethal cancers with straightforward operable measures. The majority of cancers have a long latent phase and are preceded by pre-neoplastic lesions. Early detection and treatment of cancer or precancerous lesions resulted in substantial declines in cancer mortality in high-resource countries and would greatly improve survival in low-resource countries where access to expensive cancer treatment is limited. Firm evidence of efficacy of screening programmes in the reduction of cancer mortality exists for three cancer sites: the cervix uteri, breast, and colon-rectum. In relation to the lower HDI countries in particular there is a need to evaluate alternatives to mammographic screening for early detection of breast cancer. These may initially include improvements in breast awareness among women and health workers; facilitation of access of women with clinically detectable lumps to high-quality diagnostic facilities and of women with breast cancer to effective systemic treatment. Whilst much can be achieved based on current knowledge there is an important caveat. Namely, that knowing the cause does not automatically translate to having a strategy for prevention. For example, it is likely that a large proportion of stomach cancer could be prevented by H. pylori control, but currently neither a mechanism to achieve this, nor the effectiveness if achieved, is known. In analogous fashion far more research is required into behavioural change in relation to lifestyle factors such as diet, obesity and physical activity. Even for existing prevention strategies additional work is needed on their implementation into health care settings, particularly in lower HDI countries. At the same time, for a number of major cancers (e.g., colon, prostate, kidney, pancreas, brain, lympho-haematological malignancies) research is needed to identify as yet unknown risk factors. Finally, there is a remarkable opportunity for the recent advances in understanding the molecular basis of carcinogenesis to provide new tools and insights into aetiology and prevention. Among these opportunities are: improved exposure assessment; elucidation of mechanistic pathways related to defined exposures; identification of molecular markers which indicate risk of disease progression; and stratification of cancer cases by molecular subtype in relation to specific exposures. This broader concept of translational cancer research and its potential to inform cancer prevention stands at an exciting but critical point in time. It is only by complementing efforts to improve treatment with those aimed at prevention that the impending epidemic of this disease can be addressed. Citation Format: Christopher Paul Wild. Preventable exposures associated with human cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY14-01. doi:10.1158/1538-7445.AM2013-SY14-01