© Springer International Publishing Switzerland 2015
Ramon Andrade de Mello, Álvaro Tavares and Giannis Mountzios (eds.)International Manual of Oncology Practice10.1007/978-3-319-21683-6_11. Cancer Epidemiology and Screening
(1)
Department of Medical Oncology, Federal University of São Paulo, UNIFESP, Rua Pedro de Toledo, 377, CEP 04039-031 São Paulo, SP, Brazil
(2)
Department Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal
(3)
Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal
1.1 Introduction
In the last decades, the international community has been faced with an increasing threat posed by the elevated incidence and death rates by cancer and other non-communicable diseases (NCDs) [1]. Currently, NCDs constitute the leading cause of morbidity and mortality worldwide, being recognized as a great barrier to human development and standing out as a main focus of international health discussions [2, 3]. Among the NCDs, cancer is becoming the major cause of premature deaths, surpassing cardiovascular disease, diabetes, and chronic obstructive pulmonary disease, especially in countries with a very high human development index [4].
1.2 Cancer Statistics
Excluding non-melanoma skin cancer, the global cancer incidence has increased from 12.7 million in 2008 to 14.1 million in 2012, and the expected trend is an increase in new cases to close to 25 million over the next two decades. The estimated number of cancer-related deaths in 2012 was 8.2 million, which is expected to increase to nearly 13 million by 2030 [5]. These estimates correspond with the age-standardized incidence and mortality rates of 182 and 102 per 100,000, respectively, with a slight predominance among men (53 % and 57 %, respectively) [6].
In 2012, the five most common sites of cancer diagnosed in both sexes were lung (13.0 %), breast (11.9 %), colorectum (9.7 %), prostate (7.9 %), and stomach (6.8 %). Lung cancer has the highest estimated age-standardized incidence and mortality rates (34.2 and 30.0, respectively) among men. Although prostate cancer has the second highest incidence rate (31.1), its mortality rate (7.8) is considerably lower, reflecting a lower fatality rate or improved survival. Stomach, liver, and esophageal cancers have a relatively poor prognosis, and the mortality rates are close to the incidence rates (respective incidence and mortality: 17.4 and 12.7 for stomach cancer, 15.3 and 14.3 for liver cancer, and 9.0 and 7.7 for esophageal cancer). Colorectal cancer (CRC) has an incidence rate of 20.6 and a substantially lower mortality rate (10.0) [6].
Among women, breast cancer has the highest incidence rate (43.3), followed by the cancers of the colorectum (14.3), cervix (14.0), lung (13.6), corpus uteri (8.2), and stomach (7.5). The mortality rates for cancers of the lung (11.1) and stomach (5.7) are substantially close to their corresponding incidence rate, while cancers of the breast (12.9), colorectum (6.9), cervix (6.8), and corpus uteri (1.8) have a relatively lower mortality rate [6].
The estimated prevalence shows that 32.6 million people who were diagnosed with cancer in the previous 5 years were alive in 2012. Breast cancer was the most prevalent cancer with 6.3 million survivors diagnosed within the previous 5 years, followed by prostate cancer (3.9 million) and CRC (3.5 million: 1.9 million men and 1.6 million women). Because of its very poor survival, the 5-year prevalence for lung cancer (1.9 million: 1.3 million men and 0.6 million women) was very close to the annual mortality (1.6 million) [6].
The estimated incidence rates are directly related to age. Rates for those aged 40–44 years were 150 per 100,000, which increased to >500 per 100,000 by age 60–64 years. The incidence was higher in women until about the age of 50 years, which was when the rates in men increased and became substantially higher by the age of 60 years. More cases occurred in women before the age of 50 years because of the relative earlier age of onset of cervical and breast cancers. In those aged >60 years, prostate and lung cancers in men were more frequent [6].
1.3 Cancer Burden
For all cancers combined, excluding non-melanoma skin cancer, in both sexes, the highest incidence rates occur in high-income countries (i.e., North America, western Europe, Japan, the Republic of Korea, Australia, and New Zealand). Intermediate rates are observed in Central and South America, Eastern Europe, and most parts of South-East Asia, and the lowest rates occur in most parts of Africa and West and South Asia [6–8].
Mortality rate variations have also been observed. Typically, in developed countries, breast, colorectal, and prostate cancers usually have a relatively good prognosis. Conversely, cancers of the liver, stomach, and esophagus are more common in developing countries, and have a significantly poorer prognosis [6–8].
About half of the cancer incidence concentrates in Asia, with 22 % in China and 7 % in India. A quarter of the global incidence occurs in Europe, and the remainder is observed in America and Africa. The proportional mortality distribution shows an increase in cancer-related deaths in developing countries, mainly in Asia, Africa, and Central and South America, which account for >two-thirds of the cases [9]. Since these rates are projected to increase by about 70 % worldwide in the next two decades, the greatest cancer burden will unquestionably lie in developing countries, where most of the cases are diagnosed at advanced stages. In these areas, there are also great disparities in the access to cancer care and often limited or unavailable palliative care services [10, 11].
The distribution of cancer in worldwide indicates marked differences in particular tumor types. The higher rates of cervical cancer in low-income countries contrast with the reversed trend for breast cancer, which is partly due to the heterogeneity of the health care systems and the distribution of risk factors within the countries. Population-based screening programs (e.g., mammography) have the potential to artificially increase the cancer incidence [6, 10, 11].
An analysis of cancer burden according to the region and levels of HDI revealed that the epidemiologic transition, through which low- and middle-income countries are undergoing, causes a major impact that increases population growth and ageing. Moreover, economic development, trade globalization, and urbanization facilitate the spread of risk factors such as tobacco smoking, alcohol use, an unhealthy diet, and obesity [12, 13].
In 2008, cancers of colorectum, lung, breast, and prostate were responsible for 18–50 % of the total disability-adjusted life years (DALYs) worldwide. An additional burden of 25–27 % from infection-related cancers (i.e., liver, stomach, and cervical) was observed in Sub-Saharan Africa and eastern Asia. Years of life lost (YLLs) was the main contributor of the DALYs overall, accounting for 93 % of the total cancer burden. Developing countries had a consistently higher proportion of YLLs of the total DALYs than the developed countries [7, 14].
1.4 Economic Impact
Aside from the human cost, treating and caring for an increasing number of cancer patients has a huge economic impact, raising demands on the health care budgets, even in the wealthiest nations, and it poses a major threat, especially to low- and middle-income countries, and impairs public health systems and economic development.
The Global Economic Cost of Cancer report indicated that cancer has the most devastating economic impact of all the leading causes of death in the world. The total economic burden of premature death and disability from cancer reached $895 billion in 2008, excluding direct medical costs, representing 1.5 % of world’s gross domestic product (GDP) [15].
Lung, bronchus, and trachea cancers have the largest economic cost on the global economy (about $188 billion), and it is mostly related to tobacco smoking, which justifies the international efforts for tobacco use control. Colorectal and breast cancers are the second and third largest costs (about $99 billion and $88 billion, respectively). In developing countries, cancers of the mouth, cervix, and breast have the greatest impact [16].
Since cancer is expected to become the leading cause of death worldwide, targeted prevention and treatment strategies can save lives and improve the prospects of economic development in many nations. Cancer survivorship is projected to increase because of the improvement in diagnosis due to advances in screening, detection, and treatment [17–19].
1.5 Cancer Etiology
The demographic transition is the key driver of the unprecedented growth in cancer burden. Economic development allows the increasing population growth, ageing, and the adoption of lifestyles and behavioral exposures commonly observed in industrialized countries, which account for at least 35 % of the cancers [20].
Tobacco smoking is the most important acquired risk factor. Alcohol intake, ultraviolet exposure, and ionizing radiation exposure are associated with the incidence of particular types of cancer. Eating habits also influence cancer development markedly; energy-rich and a highly processed food intake contribute to a low fruit and vegetable diet, which is associated with a lack of physical activity, being overweight, and obesity. Chronic infections play a major role in common cancers in parts of Africa and Asia, and become less important in Europe and North America [6, 21].
1.5.1 Tobacco Use
Numerous studies have shown an indubitable causal association between tobacco use and at least 14 different types of cancer, including sites that directly receive the tobacco (e.g., the oropharynx and lungs) and other sites that are reached by circulating components (e.g., the pancreas and urinary bladder). Tobacco smoke contains >7,000 chemical compounds, many of which are known carcinogens (e.g., polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines), causing harm via multiple pathways, including deoxyribonucleic acid (DNA) binding and mutations, inflammation, oxidative stress, and epigenetic changes. The risk of smoking related cancer is influenced by the number of cigarettes smoked, duration of the habit, and composition of the tobacco used [6].
1.5.2 Alcohol Consumption
Some meta-analyses established that a significant positive dose-response association exists between alcohol use and cancers of the mouth, pharynx, esophagus, colorectum, liver, larynx, and breast. According to the dose consumed, the risk of mortality seems to be exponential for the upper digestive tract (except mouth and oral cavity) and breast cancers. Survey findings indicate an important synergistic relationship between tobacco and alcohol use, which raises the risk of cancer of the oral cavity, pharynx, larynx, and esophagus [23].
Alcoholic beverages contain several carcinogenic compounds (e.g. ethanol, ethanol acetaldehyde, aflatoxins, ethyl carbamate), which probably affect different pathways. The mechanisms involved are partly understood and possibly include a genotoxic effect of acetaldehyde, the induction of cytochrome P450 2E1 and associated oxidative stress, an increased estrogen concentration, and changes in folate metabolism and in DNA repair. The consumer genotype influences the effects of alcohol consumption and the risk of digestive tract cancers. A deficiency in aldehyde dehydrogenase 2 (ALDH2) secondary to the ALDH2 Lys487 allele increases the risk of esophageal cancer for the same amount of alcohol consumed [24].
1.5.3 Diet Habit, Obesity, and a Sedentary Lifestyle
Although there is an inferred association with breast, colorectal, and prostate cancers in developed countries, fat intake has consistently shown a little relationship with their increased risk. According to several trials and a meta-analysis, a high intake of red processed meat was correlated with a greater risk of CRC [25]. The previous hypothesis associating low cancer risk to high intake of fruits and vegetables has not been supported by prospective studies [6]. Similarly, the supposed relationship between a high fiber intake and the decrease in the CRC incidence has not been confirmed by prospective surveys; however, an inverse relationship was observed in the European Prospective Investigation into Cancer and Nutrition study. A higher consumption of milk or dairy products, an increased serum vitamin D level, and folate intake was associated with a lower risk of CRC, and this was supported by the confirmed relationship between a genetic polymorphism in methylenetetrahydrofolate reductase, an enzyme involved in the folate metabolism, and the risk of CRC [6].
According to the cancer site, obesity seems to increase the incidence and mortality risks through different mechanisms, in a linear fashion with a higher body mass index. The higher prevalence of gastroesophageal reflux among obese individuals is probably associated with an increased risk for esophageal adenocarcinoma. The higher circulating estradiol in postmenopausal women, formed in adipose tissue, increases the risk of breast and endometrial cancers. For cancers of colon in men, pancreas, kidney, gall bladder in women, malignant melanoma, ovary, thyroid, non-Hodgkin’s lymphoma, multiple myeloma, and leukemia, the mechanisms involved are less clear [6].
1.5.4 Infections
There is strong evidence that relates chronic infections by biological agents as risk factors for specific cancers. The population attributable fraction for oncogenic agents of the 12.7 million new cancer cases in 2008 was 16 %, mainly due to Helicobacter pylori, the hepatitis B and C viruses (HBV and HCV), and the human papillomaviruses (HPV), which is higher in developing countries (26 %) than in developed countries (8 %). In women, cervix cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for >80 % [6, 26].
The causal association between chronic infection with Helicobacter pylori and the risk for non-cardia gastric adenocarcinoma, mucosa-associated lymphoid tissue, and diffuse large B-cell lymphoma is well established. Chronic infection with HBV is one of the most important causes of hepatocellular carcinoma (HCC) worldwide, particularly in highly endemic areas in Asia and Africa. HPV infection causes pre-cancer and cancer (mainly squamous cell carcinoma) of the cervix, anus, vulva, vagina, penis, and oropharynx.
Once the human immunodeficiency virus (HIV)-advanced infection causes immunosuppression, HIV-positive individuals have an increased cancer risk, as observed in the acquired immunodeficiency syndrome-defining cancers, Kaposi sarcoma, non-Hodgkin’s lymphoma, and cervical cancer. HIV typically coexists with oncogenic viruses, notably the Epstein-Barr virus, HPV, HBV, and HCV, and this raises the risk of lymphoma, anogenital, and liver cancer, respectively [6].
1.6 Cancer Control
1.6.1 Screening
1.6.1.1 Lung Cancer Screening
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