The most important tumor diseases: prevention and early detection

How to prevent cancer? What early detection measures are possible and what are the determining risk factors? The following article answers these questions against the background of the current state of knowledge and gives an overview of the most common tumor diseases of women and men. This knowledge is also relevant in dental practice – risk factors for common cancers are sometimes the very same ones that threaten dental health: smoking and an unhealthy diet.

  • Fig. 1: High new cancer incidence rates by age and gender, RKI Cancer in Germany 2015

In recent years, there has been a rapid development in the therapeutic options for cancer. Cancer can be cured in many cases nowadays and does not automatically mean a death sentence. However, it is necessary for the cancer to be detected at an early stage. These two factors – advances in therapy and probably also advances in the early detection of cancer – have led to a significant decline in cancer mortality in Germany over the past 20 years.

How cancer develops and progresses depends on many different factors (multifactorial); in addition, the triggers of many cancers are still unknown today. However, some risk factors are clearly documented. Factors that cannot be influenced and are associated with a higher risk of cancer include male gender, older age, hereditary predisposition (genetic disposition), living conditions (radon, UV radiation) and working conditions (e.g., hepatitis B and C).B. asbestos or benzo exposure) as well as economic, cultural and environmental conditions of influenceable risk factors such as behavior and lifestyles (e.g.B. Smoking, unhealthy diet, sunbathing, infections, such as u.a. Hepatitis and human papillomavirus [HPV]) differentiate. Approximately one-third of all cancers are due to lifestyle factors (tobacco and alcohol consumption, unhealthy diet, or lack of exercise), according to a WHO estimate, with smoking accounting for the largest proportion at about 20% [3].

Prevention

The Latin term "prevention" means "to forestall", which already indicates that the focus of medical prevention is on disease avoidance. Cancer prevention therefore includes all measures that reduce risk factors and change conditions in order to avoid developing cancer. A distinction is made between:

  • Primary prevention: This starts before the onset of the disease and aims to prevent disease from occurring in the first place.
  • Secondary prevention: Used for early detection of disease. Is intended to detect and treat the early stages of a disease and prevent progression.
  • Tertiary prevention: Comes into play after treatment of a disease and is intended to prevent secondary damage and relapse.

Primary prevention

Primary prevention of cancer is only possible if the risk factors that trigger an increased risk of cancer are known and can be influenced. According to the WHO, the most common lifestyle factors that are causally associated with an increased risk of cancer:

  • Smoking/tobacco use
  • Alcohol
  • Obesity/nutritional factors
  • Physical inactivity
  • Environment, occupational exposures
    – UV radiation
    – natural radon exposure
    – chemical factors (polycyclic aromatic hydrocarbons, aniline, benzene, asbestos)
  • Infections
    – HPV (Human Papillomavirus)
    – Hepatitis B and C
    – Helicobacter pylori
  • Fig. 2: European Code Against Cancer; © IARC 2016

Many factors that cause cancer are known. However, it is not possible to predict which individuals with a similar risk profile will develop cancer and which will not. The risk of cancer can be reduced by adherence to the European Code, but not completely eliminated. According to a WHO estimate, 30% of all cancer cases could be prevented as a result; however, some risk remains. This is because only about half of cancers are due to known causes (z.B. the majority of lung cancer cases due to smoking) [4,5] and for some cancers, the causes are still largely unknown in more than half of cases (z.B. in prostate cancer) [6].

Early detection – secondary prevention

  • Fig. 3: Adenoma-carcinoma sequence.

Colorectal cancer develops in most cases in a multistage process from benign precursors, epithelial dysplasias. Over the years, benign tumors (adenomas, in the form of tubular or villous polyps) and eventually invasive carcinomas develop on the floor of these dedifferentiated cells. A combination of exogenous and endogenous causes and risk factors is thought to lead to this sequence. Exogenous noxae include a high-fat and low-fiber diet, while endogenous noxae include genetic alterations with the loss of tumor suppressor genes (the most common gene affected in colorectal cancer is the APC tumor suppressor gene) or the activation of oncogenes (z.B. the K-RAS oncogene), which make the vulnerable epithelium of the colonic mucosa more sensitive to damaging exogenous noxae [7]. The development of carcinomas from adenomas of the colonic mucosa within the adenoma-carcinoma sequence usually takes a very long time (>10 years) (Fig. 3). Therefore, due to the long time course, early detection of the still benign precancerous lesions (polyps) in the intestine and removal of the adenomas can prevent further development into colorectal cancer.

Early detection measures are only useful for common cancers with a high mortality rate. The prerequisites for this are that effective treatment is possible in the event of a positive result, that no disadvantages or risks arise for the patient as a result of the screening measure, that the test is safe and easy to perform (acceptance by patients is otherwise low) and, of course, that an effective screening measure has been established. This means that early diagnosis also gives a better chance of cure. As disadvantages of screening measures, tumors can be detected that would have had no consequences for the patient in the following (z.B. small prostate carcinomas in older men), as they never lead to clinical symptoms. In addition, many examinations are necessary to ensure that few patients benefit, and due in part to false positive findings (z.B. in the case of mammography) can lead to a certain degree of uncertainty on the part of the patient.

Screening for colorectal cancer and cervical cancer is undisputedly useful; for prostate cancer, the choice of the best screening method is a matter of debate. In breast cancer, the benefits (earlier diagnosis of breast cancer) of mammography screening are predominantly positive and useful [8]. In part, the risk (radiation exposure) from mammography in low-risk patients is controversial, but clearly since the introduction of mammography screening, the number of breast carcinomas diagnosed at an early stage – with a resulting better prognosis – has increased significantly. Therefore, good patient education is essential prior to any screening measure. In Germany, only one in two women over 30 years of age and one in five men make use of the statutory screening examinations. These figures must be improved in Germany in the coming years – through targeted education, measures and strategies by physicians, health insurance companies, health advisors and the public.

  • Table 1: Statutory screening program.

In Germany, statutory screening is provided for the following cancers, d.h., the costs are covered by the health insurance companies (Tab. 1):

  • Cervical cancer
  • Colorectal cancer
  • Breast Cancer
  • Skin cancer
  • Prostate cancer

The most frequent tumor diseases

  • Fig. 4: Percentage of most common new cancer cases in Germany 2012 ( RKI, Cancer in Germany 2015).

Colorectal cancer screening

In Germany, approx. 61.000 people with colorectal cancer. Colorectal cancer is the third most common tumor in men and the second most common tumor in women. The lifetime risk of developing colorectal cancer is 0.6%. The median age of onset is 71 years for men and slightly higher for women (75 years).

The incidence, d.h. the number of new cases, has recently slightly decreased in Germany, likewise the mortality for colorectal cancer has significantly decreased in the last 10 years [2]. This is due on the one hand to the introduction of early detection measures (colorectal cancer screening) and on the other hand to an improvement in therapy. The prognosis depends on the stage; it gets worse as soon as the tumor has spread to the lymph nodes, and it gets worse if there are metastases in the organs (distant metastases). The five-year survival rate is 90% for localized stages (UICC I), 50% for lymph node metastases (UICC III) and 10% for distant metastases (UICC IV).

Risk factors for colorectal cancer are considered to be:

  • genetic disease patterns, most frequently the so-called hereditary colorectal carcinoma or also HNPCC or. Lynch syndrome as well as familial adenomatous polyposis (FAP) before
  • A familial burden (disease of one or more first-degree relatives< 50 years)
  • the presence of polyps (adenoma-carcinoma sequence)
  • Chronic inflammatory bowel diseases (ulcerative colitis, Crohn’s disease)
  • The lifestyle factors of smoking, a diet high in alcohol, a low-fiber and high-fat diet high in red meat and processed meats, and low vegetable intake are risk factors, as are physical inactivity and obesity.

The long time course from the appearance of polyps to the development of a carcinoma offers a very good opportunity for screening and early detection. The screening measures should be applied to the asymptomatic population without familial risk factors from the age of 50. Start at the age of. Statutory colorectal cancer screening was introduced in Germany in 2002 and provides for the following measures:

From the 50. A digital rectal examination every year before the age of 50 and every year between the age of 50 and the age of 18. and 54. In the second half of life, a test for occult (= hidden) blood in the stool is.

From the age of 55. The first colonoscopy at the age of 10 years, with repeat colonoscopy after 10 years if the findings are normal. In the case of abnormalities depending on the findings earlier (z.B. if polyps were found) (Tab. 1). Alternatively, patients who refuse colonoscopy at age 55 can be tested for occult blood every two years. However, only colonoscopy can detect polyps and thus achieve good prevention. For both screening measures, occult blood test and colonoscopy, a reduction in cancer-specific mortality (= mortality) has been shown since introduction into colorectal cancer screening [9,10].

Breast Cancer Early Detection

In Germany, about 75.000 women per year die of breast cancer. Breast cancer is the most common tumor disease in women, accounting for 31% of all cancers. The lifetime risk of developing breast cancer for girls born in Germany in 2008 is 9%, the median age of onset of breast cancer is 64 years [2]. The incidence is continuously rising in Germany; especially since 2009, after the introduction of nationwide mammography screening, a sharp increase in the number of new cases has been observed. Cure rates and survival times have recently improved significantly due to advances in therapy as well as breast cancer screening (tumors are detected at an earlier stage). The five-year survival rate in Germany is currently 79%, and significantly higher for patients with a localized stage.

In breast cancer, risk factors include:

  • genetic factors, the best known being the BRCA 1 and 2 mutations
  • a familial burden (increased incidence of breast or ovarian cancer on one side of the family)
  • hormonal influences (early menarche, late menopause, late or no pregnancy, hormone replacement therapy and obesity)
  • toxic factors (radiation exposure of the breast)
  • Lifestyle factors: high alcohol consumption and smoking

Breast cancer screening cannot prevent cancer, but it can detect and treat cancer at an earlier stage. Currently, breast cancer screening is provided for three target groups:

Women between the ages of 50 and 69: Compared to younger women, this age group has a significantly higher rate of new cases and is therefore the target group for the classic German mammography screening program (early detection of breast cancer) by means of mammography every 2 years (Tab. 1).

Hereditary breast cancer: Women who have a pathogenic germline mutation or a familial burden have a dramatically increased lifetime risk of developing breast cancer compared to the normal population (for BRCA-1 and BRCA-2 mutation carriers 60-85%). The disease also occurs significantly earlier, at a younger age (median age of onset 44 and 47 years) compared to the normal population [8]. For these women, an intensified screening program is offered, which according to risk starts at a younger age (from 25-30 years), includes shorter examination intervals and other methods (additionally mammary sonography and MRI = magnetic resonance imaging) [8].

After radiation to the breast in childhood or adolescence:

The risk of breast cancer after radiation (latency approx. 30 years after the end of radiotherapy) of the breast in childhood or adolescence is significantly increased and at ages between 24 and 45 years ca. 24 times higher than in the normal age-matched population [11]. Improvements in radiation technology with lower radiation doses and smaller radiation volumes, as well as improvements in chemotherapy protocols with better response rates, so that radiotherapy can be omitted [12,13], are expected to decrease this risk group in the future.

Since the introduction of breast cancer screening, more advanced tumors with unfavorable prognosis are diagnosed less frequently. Mammography in asymptomatic women has been shown to reduce cancer-specific mortality (= mortality) by 19 to 23% [14].

Prostate cancer early detection

In Germany, approx. 65.000 men per year from prostate cancer. Thus, prostate cancer is the most common cancer in men, accounting for 26% of all new cases. Incidence has been steadily increasing for three decades [2]. This is mainly due to the use of new methods for early detection (z.B. PSA screening). This means that carcinomas are detected earlier. Due to increasing life expectancy and the resulting aging of the population, the number of new cases will continue to rise in the coming years. The median age of onset is 70 years; the lifetime risk of developing prostate cancer is 13%, but the risk of dying from prostate cancer is only 3%. This discrepancy is due to the particular tumor biology of prostate carcinoma. The vast majority of prostate cancers remain indolent throughout life, d.h., the tumor does not metastasize, the patient has no symptoms and does not die from the disease. Only a small proportion of prostate carcinomas behave aggressively at diagnosis or during the course of the disease. That is, 5 out of 6 men diagnosed with prostate cancer die not from cancer but from another cause. The five-year survival rate for prostate cancer is therefore very high at 93%.

Risk factors

Only a few established risk factors are known for the development of prostate carcinoma [15], the most important ones being:

  • higher age
  • the ethnic background (z.B. African-Americans develop the disease more frequently, while Asians rarely do)
  • a positive family history
  • rare inherited syndromes (BRCA mutations), and
  • a chronic prostatitis.

Lifestyle factors are not known to play a role in the development of prostate cancer [16,17].

Early detection

In principle, prostate carcinoma is suitable for treatment due to the long time course from the appearance of first histological changes or. of a PSA increase until the first clinical symptoms appear for early detection.

Digital rectal examination (DRU)

The digital rectal examination is one of the statutory preventive examinations for men aged 45 and over, which is paid for by the health insurance funds (Tab. 1). The specificity (true negative) of this test is high, however the sensitivity (true positive) is low [18]. Whether this screening measure has an influence on cancer-specific survival has not been proven by studies.

PSA screening

PSA (prostate specific antigen) is an enzyme that is formed in the epithelia of the prostate gland and is elevated in prostate cancer. Small elevations can also occur in benign prostate diseases (benign prostatic hyperplasia, prostatitis).

The population-based PSA screening, d.h. Regular PSA testing of all men over a certain age, is controversial. PSA testing, as proven by studies, can significantly reduce cancer-specific mortality (relative reduction of mortality by 27%) as well as metastasis [19]. However, population-based screening diagnoses and treats many prostate cancers at an early stage that might never have become symptomatic in the course – with the resulting side effects and loss of quality of life.

Therefore, studies are currently investigating whether age-adapted screening (baseline PSA level at age 45 to 50 years) can identify risk groups based on the level of PSA that have a higher risk of developing clinically significant prostate cancer.

Summary

30% of all cancers can be prevented by preventive measures. For many cancers (not all), avoiding risk factors can reduce the risk of disease. For some cancers, early detection measures can detect the cancer or precancerous lesion at an early stage and thereby improve treatment. Statutory screening examinations are available in Germany for skin, breast, intestinal, cervical and prostate cancer.

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