Molecular Biology of Cancer BC 504 Past Paper PDF

# Molecular Biology of Cancer BC. 504 ## Cancer Epidemiology - Cancer incidence and mortality are rapidly growing world-wide. - This is due to several factors, including aging, growth of the population, and changes in the prevalence and distribution of the main risk factors for cancer. ## Distri...

# Molecular Biology of Cancer BC. 504 ## Cancer Epidemiology - Cancer incidence and mortality are rapidly growing world-wide. - This is due to several factors, including aging, growth of the population, and changes in the prevalence and distribution of the main risk factors for cancer. ## Distribution of Cases and Deaths for the 10 Most Common Cancers ### Incidence - **Both Sexes** - Lung: 31.6% - Breast: 11.6% - Colorectum: 10.2% - Prostate: 7.1% - Leukaemia: 3.2% - Cervix uteri: 3.3% - Bladder: 3.0% - Thyroid: 3.1% - Cervix uteri: 3.2% - Esophagus: 3.2% - Liver: 4.7% - Total: 18.1 million new cases - **Males** - Lung: 14.5% - Other: 30.6% - Leukaemia: 2.6% - Kidney: 2.7% - Non-Hodgkin lymphoma: 3.0% - Esophagus: 4.2% - Bladder: 4.5% - Colorectum: 10.9% - Stomach: 6.3% - Liver: 7.2% - Total: 9.5 million new cases - **Females** - Other: 28.9% - Breast: 24.5% - Lung: 13.7% - Colorectum: 9.4% - Leukaemia: 3.0% - Esophagus: 3.8% - Ovary: 4.7% - Non-Hodgkin lymphoma: 2.6% - Liver: 3.0% - Ovary: 3.4% - Stomach: 4.0% - Corpus uteri: 4.5% - Thyroid: 4.9% - Cervix uteri: 6.5% - Total: 9.2 million new cases ### Mortality - **Both Sexes** - Lung: 18.4% - Other: 29.3% - Colorectum: 9.2% - Stomach: 8.2% - Liver: 8.2% - Pancreas: 4.5% - Breast: 6.6% - Esophagus: 5.3% - Total: 9.6 million deaths - **Males** - Lung: 22.0% - Other: 23.0% - Colorectum: 9.0% - Stomach: 9.5% - Liver: 10.5% - Prostate: 6.7% - Leukaemia: 3.3% - Pancreas: 4.2% - Esophagus: 6.6% - Bladder: 2.8% - Non-Hodgkin lymphoma: 2.7% - Total: 5.4 million deaths - **Females** - Other: 25.4% - Lung: 8.4% - Colorectum: 9.5% - Stomach: 7.7% - Cervix uteri: 6.7% - Breast: 15.6% - Liver: 6.0% - Pancreas: 4.9% - Ovary: 3.4% - Thyroid: 4.9% - Corpus uteri: 6.5% - Total: 4.4 million deaths ## Top Leading Cancer Types for the Estimated New Cancer Cases and Deaths by Sex, United States, 2023 ### New Cases: | Type | Males | Females | |---|---|---| | Prostate | 288,300 | 297,790 | | Lung & bronchus | 117,550 | 130,790 | | Colon and rectum | 81,860 | 71,600 | | Urinary bladder | 62,420 | 62,800 | | Melanoma of the skin | 58,120| 58,610| | Kidney & renal pelvis | 52,360 | 49,640 | | Non-Hodgkin lymphoma | 44,880 | 44,500 | | Thyroid | 39,290 | 39,510 | | Oral cavity & pharynx | 35,670 | 33,820 | | Pancreas | 33,130 | 33,410 | | Leukemia | 31,010 | 30,590 | | **All sites** | **1,010,310** | **940,000** | ### Deaths: | Type | Males | Females | |---|---|---| | Lung & bronchus | 87,160 | 59,910 | | Prostate | 34,700 | 43,110| | Colon and rectum | 28,410 | 24,080 | | Pancreas | 26,620 | 23,930 | | Liver & intrahepatic bile duct | 19,000 | 13,270 | | Leukemia | 13,900 | 9,810 | | Urinary bladder | 12,160 | 13,030 | | Esophagus | 12,920 | 13,030 | | Non-Hodgkin lymphoma | 11,780 | 8,400 | | Brain & other nervous system | 11,020 | 7,970 | | **All sites** | **322,080** | **287,740** | ## The Most Frequent Cancers in Egypt Estimated Using the Results of the National Population-Based Registry Program of Egypt 2008-2011. | Site | % | Crude rate | ASR | |---|---|---|---| | Liver | 39.5 | 61.8 | 33.63 | | Bladder | 12.6 | 21.1 | 10.71 | | Lung | 6.7 | 10.4 | 5.69| | Non-Hodgkin lymphoma | 6.4 | 8.8 | 5.48| | Brain | 6.4 | 8.8 | 5.48| | Prostate | 5.0 | 9.3 | 4.27| | Breast | 13.54 | 35.8 | 32.04| | Brain* | 4.6 | 5.8 | 5.18| | Ovary | 1.2 | 48.8 | 4.12| | Non-Hodgkin lymphoma | 3.7 | 6.3 | 3.80| | Thyroid | 3.7 | 6.1 | 3.28| | Liver | 27.5 | 43.6 | 23.81| | Breast | 17.8 | 24.3 | 15.41| | Bladder | 8.0 | 13.5 | 6.94| | Brain* | 6.1 | 8.5 | 5.29 | | Non-Hodgkin lymphoma| 5.4 | 7.5 | 4.64 | | Lung | 4.9 | 7.5 | 4.22 | *Includes trachea, bronchus, and lung tumors. ## Cancer Statistics - Cancer ranks as a leading cause of death and an important barrier to increasing life expectancy in every country of the world. - It is the first or second leading cause of death before the age of 70 years in 112 of 183 countries, and ranks third or fourth in another 23 countries. - Overall, the burden of cancer incidence and mortality is rapidly growing world-wide. - This reflects both aging and growth of the population, as well as changes in the prevalence and distribution of the main risk factors for cancer. - Several risk factors are associated with socioeconomic development. - We use "transitioning, emerging, and lower HDI countries/economies" as synonyms for nations classified as low or medium HDI, and we use "transitioned or higher HDI countries/economies" for those classified as high or very high HDI. ## Top 10 Cancer Types - The top 10 cancer types account for >60% of newly diagnosed cancer cases and >70% of cancer deaths worldwide. - **Combined** - Female breast cancer (11.7% of total cases) is the most commonly diagnosed cancer, followed by lung (11.4%), colorectal (10%), prostate (7.3%), and stomach (5.6%). - Lung cancer (18% of total cancer deaths) is the leading cause of cancer death, followed by colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and female breast cancer (6.9%). - **Men** - Lung cancer is the most frequently occurring cancer, followed by prostate and colorectal cancer for incidence, and liver and colorectal cancer for mortality. - **Women** - Breast cancer is the most commonly diagnosed cancer, followed by colorectal and lung cancer for incidence, and vice versa for mortality. ## Future Burden of Cancer in 2040 - Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040. - This is a 47% increase from 2020. - It is assumed that national rates estimated in 2020 remain constant. - The relative magnitude of increase is most striking in low HDI countries (95%) and medium HDI countries (64%). - In terms of absolute burden, high HDI countries are expected to experience the greatest increase in incidence, with 4.1 million new cases more in 2040 compared with 2020. - Increases in the incidence of these cancers will likely be paralleled by increases in mortality rates. - This is unless resources are placed within health services to appropriately treat and manage the growing number of cancers. ## Cancer Incidence In Egypt - In 2020, the incidence rate of total cancer cases in Egypt has increased by 4.5% with 134,632 cases. ## Number of New Cancer Cases in Egypt - There are several charts comparing numbers of new cancer cases in 2018 and 2020. - One chart shows the breakdown of new cancer cases by sex, both males and females, in 2020. ## What Is Cancer? - There is a need to understand the disease and translate knowledge into effective therapies. - Cancer is a group of diseases in which cells grow and divide uncontrollably, forming a mass called a tumor. - Cancer cells can invade nearby tissues and spread to other parts of the body. - Metastasis means that cancer has spread from the primary site to other sites. - This is done through the bloodstream or lymphatic system. ## Tumor Classification: Benign vs Malignant - A tumor is an abnormal mass in the body that grows due to cells reproducing too much (hyperplasia) or not dying when they are supposed to. - Tumors are classified as *benign* or *malignant* based on several characteristics. ### Benign Tumors: - Grow slowly and have distinct borders. - Do not invade surrounding tissue. - Do not invade other parts of the body. ### Malignant Tumors: - Can grow quickly and have irregular borders. - Often invade surrounding tissue. - Can spread to other parts of the body through a process called metastasis. ## The Tissue of Origin Gives the Distinguishing Characteristics of the Cancer - The tissue of origin gives the distinguishing characteristics of the cancer. - **Carcinoma** - This type of cancer originates from the epithelial layer of cells that form the lining of external parts of the body or the internal linings of organs within the body. - There are three types: - Myeloma, which originates in the plasma cells of bone marrow - Sarcoma, which originates in connective and supportive tissues, including muscles, bones, cartilage and fat. - Lymphoma, which originates in the lymphatic system. - **Leukemia** - This is a group of cancers that are grouped within blood cancers. - **Mixed type** - These have two or more components of the cancer. ## Cancers By Cell/Tissue Type - **Carcinomas** - Epithelial cells (skin, body cavities, organs) - **Sarcomas** - Bones and soft tissues - **Myelomas** - Plasma cells (manufacture antibodies) - **Leukemias** - Blood cells (originates in bone marrow) - **Lymphomas** - Immune system (lymph nodes, spleen, stomach, testicles) - **Mixed types** - Derive from multiple cell/tissue types ## Cancer Based On Tissue Type - **Carcinomas** - Adenocarcinoma - Squamous cell caremoma - Basal cell carcinoma - Transitional cell carcinoma - **Sarcomas** - Angiosarcoma - Osteosarcoma - Ewing's sarcoma - Chondrosarcoma - Liposarcoma - Fibrosarcoma - Hemangioendothelioma - **Leukemias** - Lymphoma - Myeloma - **Gastrointestinal Stromal Tumor** - **Mesenchymal Neoplasms of the Gastrointestinal Tract** ## How Cancer Arises? Cancer originates from a single abnormal cell (clonal origin). Changes in the DNA sequences result in the cell progressing slowly to the mildly aberrant stage. Successive rounds of mutation and natural selection lead to a mass of abnormal cells called tumors. Some cells in the tumor undergo further rounds of mutations leading to the formation of malignant cells, which cause metastasis. ## Insights Into Cancer - Initiation and progression of cancer depends on both external factors in the environment (tobacco, chemicals, radiation, and infectious organisms) and factors within the cell (inherited mutations, hormones, immune conditions, and mutations that occur from metabolism). - These factors can act together or in sequence, resulting in abnormal cell behavior and excessive proliferation. - As a result, cell masses grow and expand, affecting surrounding normal tissues and can spread to other locations in the body (metastasis). - However, it is important to remember that most common cancers take months and years for these DNA mutations to accumulate and result in a detectable cancer. ## Molecular Basis of Cancer - The evolution from a normal cell to metastatic cancer cell requires multiple genetic and epigenetic changes. - There are at least three mechanisms that allow these changes to be transferred to the progeny of a malignant cell: an inherited mutation, a somatic mutation, and methylation of the cell's DNA. - These genetic events typically affect at least four pathways, but the order in which the genes are affected is not critical. ## Malignant Transformation Multi-Step of HCC - The chart in the document shows liver cell transformation. - It starts with normal liver cell. - Then hepatitis B or C, ethanol, and NASH can activate stellate cells and cause hepatocyte senescence and necrosis. - Next, there are epigenetic alterations, genetic alterations, dysplastic nodules, and finally liver cirrhosis. - Eventually, the tumor develops into HCC. ## Multistep Genetic Model for Colorectal Adenocarcinoma Sequence - A mutation in the APC tumor suppressor gene is generally considered to be the initiation event. - This is followed by the sequential accumulation of other epigenetic and genetic changes that eventually result in the progression from a normal cell to a metastatic tumor. ## Hallmarks of Cancer Cell - There are six essential alterations in cell physiology that collectively dictate malignant growth: - self-sufficiency in growth signals, - insensitivity to antigrowth signals, - evasion of apoptosis, - limitless replicative potential, - sustained angiogenesis, and - tissue invasion and metastasis. - These six capabilities are shared in common by all types of human tumors. - Although virtually all cancers must acquire these six hallmark capabilities, their means will vary both mechanistically and chronologically across tumor types. - As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. - These include deregulating cellular metabolism and avoiding immune destruction. - They are now considered to be core hallmarks of cancer. ## Risk Factors for Development of Cancer - Cancer development is dependent on both intrinsic (unmodifiable and partially modifiable) and extrinsic (modifiable) risk factors. - **Intrinsic risk factors:** - Random errors in DNA replication - **Endogenous risk factors**: - Biological aging - Genetic susceptibility - DNA repair machinery - Hormones - Growth factors - Inflammation - **Exogenous risk factors**: - Radiation - Chemical carcinogens - Tumor causing viruses - Bad lifestyles (smoking, lack of exercise, nutrient imbalance, etc.)