Risk factors of cancerUnmodifiable factors, such as age and modifiable lifestyle factors impact the forming of cancers. Some factors increase the risk of developing cancer, and some decrease it. Key points Most cancers are associated with aging. The longer a person lives, the more likely it is that cancer causing lesions accumulate in their cells. It is estimated that more than 40 percent of all new cancer cases could be avoided by changing the risk factors which individuals can influence. The single biggest risk factor is smoking, which explains even up to 20% of all new cancer cases. The developing of cancer is a series of events over a period of many years, during which originally healthy genetic cell material is damaged and the cells change through a number of intermediate stages of the body into tissue independent of the body’s regulatory systems. As it grows, the malignant tissue eventually causes symptoms.See an animation of the initiation of the cancer process. In the majority of cancer cases the specific cause of the disease cannot be identified. Cancers are a diverse group of diseases, and their causes, progression, symptoms and treatment can differ a great deal from each other. Human factors related to behavior and living habitat are relevant in the development of most cancers. Although individual susceptibility might be a factor associated with some cancers, external factors are needed almost always for a cancer to develop. For the sake of cancer prevention and the cancer burden of the entire population, it is vital to know the factors that impact the development of cancer probability in the Finnish population specifically. Cancer risk factors can be roughly divided into the following categories: internal factors, such as age, sex, metabolism of substances foreign to the body, inherited genetic defects and non-inherited gene disorders, as well as the type of skin, lifestyle related factors, occupational exposures, e.g. many chemicals, radioactive materials and asbestos, environmental exposure, e.g. radon and UV radiation, as well as small particles. Attributable proportions of risk factors Attempts have been made to relate different risk factors associated with cancer with each other. It is estimated that by changing the risk factors for cancer, which individuals can influence with their own actions, an estimated 43% of all new cancer cases could be avoided. The biggest single factor is smoking, which accounts for up to 20% of all new cancer cases. [1, 2] Table 1 lists some of the most common, modifiable risk factors of the incidence proportions of cancers. It should be noted, that the importance of the various factors on the population level will vary according to regional conditions, and the health and socio-economic behavior of the population.  Age Most cancers are associated with aging. The longer a person lives, the more likely it is that cancer causing lesions accumulate in their cells. The ability of cells to prevent and recover from these defects weakens with age. Gender There are clear differences in the prevalence of also other cancers than those related only to gender (such as ovarian cancer and prostate cancer) among men and women. For example, the age-adjusted morbidity of laryngeal cancer in men is nearly ten-fold compared to women. The difference in lung and lip cancers is now less than three-fold, while it was 15-fold until the 1960s. These changes can be explained largely by the fact that the smoking habits of men and women have evolved in different ways in the past decades. Heritability The tumor or cancer cell is neither contagious nor hereditary. Instead, susceptibility to an increased risk of developing cancer can be inherited. In this case, a change in the inheritance factor in cancer development is already in place in all human cells, and it can be passed on to offspring along with the gamete. In addition, environmental factors are most often needed to cause other required changes necessary for the development of a malignant tumor in most cases. Regarding cancer heritability see “Cancer in the family” Living habits Tobacco. The use of tobacco products is the single most important factor in increasing cancer risk. The hazards of tobacco are due to a large amount of carcinogenic compounds: those which are already in the tobacco product and those that form during smoking. The impact that smoking has on lung cancer development is best known. The probability of developing lung cancer is the greater the younger people start smoking, the more they smoke on a daily basis, and the longer they continue smoking. [4, 5] If a person has smoked 20 cigarettes a day for 50 years, his chances of developing lung cancer is almost 50-fold compared to non-smokers. After quitting smoking, the risk of lung cancer rather quickly approaches those of non-smokers the same age, but it does not drop to the same level. People who have smoked the longest, benefit the most from quitting. Smoking is a major cause of cancer of the larynx, and it also has impact on the development of oral, pharyngeal, kidney, pancreatic, esophageal, cervical and bladder cancer. Smoking might slightly increase the risk of breast cancer, too.  In recent years, clear evidence on carcinogenic potential of the use of snus has accumulated in research. For those using snus the risk of developing oral and pharyngeal cancer, pancreatic and gastric cancer and esophageal cancer is much higher than those who do not use tobacco products. [7-9] Electronic smoking has increased significantly during recent years. Its impact on health is being studied. The risk of cancer often increases significantly with the combination of smoking and other factors. Together, smoking and outdoor work, e.g., multiply the risk of lip cancer by as much as 15-fold, even though outdoor work or smoking on their own only double the risk of lip cancer.  Smoking increases the impact of asbestos and many substances used in the working environment, which are not notably dangerous on their own. Alcohol. There is a clear causal relationship between the use of alcoholic beverages and several types of cancer. There is convincing evidence that heavy use of alcohol increases risk of oral, pharynx, larynx, esophagus, liver, bowel and breast cancers.  (www.dietandcancerreport.org) Four daily doses of alcohol (50 grams of ethanol), for example, approximately doubles the risk of oral and pharyngeal cancer. Other factors may increase the effect of alcohol. For example, drinking alcohol and smoking together increase the risk of oral, pharynx and larynx cancers very strongly. Regarding breast cancer there is no safe amount of alcohol use, but the risk of cancer is increased in direct proportion to the amount of alcohol consumed on a regular basis. The most important risk factor is the amount of ethanol consumed. Heavy alcohol use increases the risk of cancer and causes other clear health problems. The type of alcoholic beverages consumed does not significantly impact the risk of cancer risk. Nutrition. Diet is a complex mix of components, which have joint and contrary effects that are difficult to reliably estimate. Nutrition is considered to have the most effect on gastric, lung and breast cancer of the esophagus, colon, rectum, bladder, prostate and endometrial cancer risk. These are common cancers in Finland and other Western countries. Dietary fat increases, according to a number of animal tests, the risk of breast, colon and pancreatic cancer. Information on people however, is not yet convincing enough to enable definite judgment on fat’s effects on cancer risk. Cancer tissue needs energy and minerals, so nutrition can impact not only on the development of cancer, but also its growth. Dietary fibers are likely to protect against colorectal cancer.  Root vegetables and rye bread, included in traditional Finnish diet, are also healthy in this respect. In addition, fruit and vegetable rich diets reduce the risk of many cancers. The effect of red and processed meat on the incidence of some types of cancer has been studied extensively. Heavy consumption of processed meat is associated with an increased risk of colorectal and gastric cancer. Red meat is also a likely risk factor of colorectal as well as pancreatic and prostate cancer.  The main interest regarding the connection of vitamins and cancer has been in carotenoids, vitamins A, E, C, and D and folate. Vitamin products have also been studied for the prevention of cancer, but none of them have yet been shown to prevent cancer alone or in any combination.  Therefore, it seems that the deciding factor in terms of cancer prevention is balanced overall nutrition, not individual dietary factors. Some food preparation processes cause chemical changes which result in cancer-causing substances forming in the food. Smoking and grilling fatty food over an open fire or other high temperature generates small amounts of polycyclic aromatic hydrocarbons (PAHs) on the surface of the food, which increase the risk of cancer. The high consumption of salt and of foods conserved in salt increase the risk of gastric cancer. Exercise and weight control. The link between physical activity and the risk of cancer has been found in numerous studies. Scientific evidence has accumulated indicating that physical activity protects in particular from breast, colon, endometrial and prostate cancer (www.dietandcancerreport.org). Moderate physical activity changes the metabolism of certain hormones and enhances the body’s general defense mechanisms. Exercise reduces the amount of fat tissue, and the situation of various growth factors in the body becomes more balanced. People who exercise more often also often have more cancer protective ingredients in their diet. According to recent studies, a total amount of about one hour of daily physical activity in form of everyday or beneficial activity, such as walking or biking to work or to the store, climbing the stairs or working the yard is adequate. Especially, people doing sedentary work should exercise regularly in order to prevent overweight. Swift exercise several days a week can increase the cancer protective effect of physical activity.  Reproduction and hormones. Female genital cancers and breast cancer are clearly linked to sexual and reproductive behavior. If a woman has had multiple sexual partners, she is more likely to get cervical cancer. The number of sexual partners of their male partner also has an impact on women’s risk of developing cervical cancer. This can be explained by the fact that infectious viruses by sexual contact are important in the pathogenesis of cervical cancer (see below: Infections.) Giving birth at young age and having many children protects against breast cancer. The protective effect is emphasized if the woman has a very large number of children.  Infertility is a risk factor also in ovarian and endometrial cancer. Early sexual maturity and late menopause increase the number of menstrual cycles and the risk of the aforementioned cancers. Breast, endometrial and ovarian cancers are diagnosed more often in women using long-term hormone therapy during menopause. [17-19] Progesterone, associated with estrogen replacement therapy increases the risk of breast cancer, but, in turn, protects from endometrial cancer. [17, 18, 20] The benefits of estrogen replacement therapy in treating menopause should therefore be weighed individually, in relation to the risk of cancer, among other things. Concerning men, high male hormone i.e. androgen level is likely to be associated with a higher risk of prostate cancer. Cosmetics. We are exposed, intentionally or unintentionally, to a wide range of chemicals in everyday life. Among other things, links with the use deodorants and hair dyes to cancer risk has been researched in several studies. Some studies have found that the use of hair dyes slightly increase the incidence of, e.g., bladder and breast cancer, but there is not sufficient evidence on their definite role as a potential cancer risk factor. [21-24] Infections. Some viral infections increase the risk of cancer. Also infections caused by the bacteria may increase the risk of certain cancers. The most studied virus family causing cancer risk are papillomaviruses (HPV, human papilloma virus), some of which result in chronic inflammation and thus cervical cancer.  Papilloma viruses may also cause other cancers, such as pharyngeal cancer.  Vaccines for the prevention of infections caused by the papilloma virus have been available for a few years, and for girls, HPV vaccination is part of the national vaccination program in Finland. Ongoing long-term follow-up studies are set to find out to what extent HPV vaccines also prevent cancer.  The bacteria Helicobacter pylori increases the risk of gastric cancer.  Chronic liver inflammation (hepatitis B and C virus infections) is associated with an increased risk of liver cancer. A hepatitis B virus (HBV) vaccination campaign, started in 1984 in Taiwan, first led to a decline in the prevalence of HBV and, subsequently, to a significant reduction in the incidence of liver cancer in the vaccinated age groups.  Table 1. Percentages of incident cancer cases attributable to different modifiable risk factors (all cancers). Work-related exposures The impact of work-related exposures, such as chemicals, on cancer risk has been studied in hundreds of separate studies. On the Finnish Institute of Occupational Health’s web site you can find good information about dangerous exposures to cancer in the work environment and on their measurement. Cancer risk related to various professional groups is systematically examined in a large Nordic NOCCA study. The NOCCA study confirms already known links between certain professions and cancer hazards, as well as provides an indication of the importance of choices associated with occupational exposures and lifestyle. More detailed information on profession-related cancer risks can be found in a joint Nordic NOCCA project’s site . The increase of sedentary work reduces physical activity, which has protective properties against cancer. The lack of physical activity and abundant sitting is harmful to health in many ways.  Shift work is currently also considered to increase the risk of cancer. . Also, mine workers and seamen are diagnosed with 20-30% more cancers than Finnish men on average (Table 2). The sun’s ultraviolet radiation plays a role in cancer risk for certain professions. For example, lip cancer is found most often in fishermen and farmers, while the risk of cutaneous melanoma is the largest in indoor workers whose unaccustomed skin burns easily during holiday periods. Finnish women’s risk of cancer is the highest in safety work, which includes, for example, police and security work. Next on the list are dentists and doctors. Cancer risk is in turn significantly lower than the average for example in farmers and gardeners. Table 2. Occupations with the lowest and highest cancer morbidity in Finland in 1971-2005: The numbers of cancers (N) and the difference in cancer risk (%) compared to the population average (46). All shown percentages are statistically significant. Environmental exposures Pollutions of the living environment. Air pollution, mainly emissions from industry and traffic, increase the risk of lung cancer to some extent. However, men’s lung cancer is most often found in those parts of Finland where the air is cleanest. Air pollution is a negligible risk factor compared to tobacco. Yet studies are currently ongoing among other things, on what connection wood-heated houses and small particle emissions have with cancer.  The production of drinking water by surface water chlorination generates mutation-causing compounds which may slightly increase the risk of, for example, genitourinary cancer.  The arsenic in drilled well water appears to have a similar effect.  Measurement results describing the state of the environment have been produced increasingly in recent years, and they can be utilized to better assess the causes of cancer risk. An example of such is an environmental health study of people who once lived in houses built–and later demolished–on top of a former landfill in Myllypuro, Helsinki. According to the first survey some more cancer and asthma was discovered in the residents of these houses, compared to reference residents , but according to the latest studies, those who lived in the Myllypuro area were not diagnosed with cancer more often than people living in any other area in Helsinki in the 2000s.  Ionizing radiation occurs everywhere, because radiation can be found e.g. in the earth crust’s natural radioactive substances, which are transported into the human body via nutrition. The main source of radiation for the Finnish population is indoor air radon, which provides an average amount of 2 mSv per year, i.e., about half of the total radiation dosage. Inhalation of radon causes a radiation dosage primarily only in the lungs. The only clearly established health effect of radon is the increased risk of lung cancer. The risk of lung cancer caused by radon is higher in smokers than non-smokers. It is estimated that radon in the indoor air, in conjunction with smoking, causes approximately 300 lung cancers every year.  X-ray radiation is used in radiology and various forms of radiation are used in radiation treatments. In health care, it should therefore always be assessed carefully, if the benefit achieved with the use of radiation is greater than the risk caused by it. Cancer patients undergoing radiation treatment receive very high radiation dosages, and in addition to the tumor, other tissues may be exposed to radiation as well. Patients treated with radiation therapy are at increased risk of developing leukemia and some other cancers [38-43], but the benefits of treatment are far greater than the disadvantages. Ionizing radiation has been estimated to cause 1-3% of all cancers. Radiation increases particularly strongly the risk of leukemia, as well as thyroid, breast, lung and bladder cancer. Non-ionizing radiation includes ultraviolet radiation, as well as the magnetic and electric fields. Ultraviolet radiation is obtained primarily from sunlight and sunbeds, and it causes skin cancers. The main cause of cutaneous melanoma is repeated burning of the skin due to excessive UV radiation, especially in childhood and youth. Particularly at risk are fair-skinned, blue-eyed people with easily burning and poorly tanning skin. Power cords and electrical equipment create very low frequency magnetic fields (50-60 Hz) around them. Their effect on the risk of cancer and, above all, the risk of childhood leukemia has been studied on several occasions, but the results have been inconsistent. According to Finnish comprehensive series of studies on the entire population, the risk of cancer in children or adults is not increased in the vicinity of power lines. [44, 45] The frequency of radio frequency magnetic fields is millions of hertz. They are created by, among others, radar, radio transmitters, mobile phones and base stations. Radio frequency radiation does not cause mutation and has not increased cancers in animal tests. 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