Cancer

In many states cancer is the leading cause of death, as well as in Hispanic and Asian Americans and people under age 80.Global cancer rates are increasing, with an associated rise in the number of cancer survivors living with symptoms and disabilities as a result of their disease and for its treatment.

One in 5 men and one in 6 women worldwide develop #cancer during their lifetime-WHO.

The lifetime probability of being diagnosed with invasive cancer is slightly higher for men at 39.3% than for women 37.7% which may reflect differences in environmental exposures, and endogenous hormones.

Incidence rates for most cancers are higher in men than in women, and the difference remains enigmatic.

Taller  stature is consistently associated with an increased risk of many cancers in large population-based studies, and this holds for both genders and across different ethnicities.

One in 8 men and one in 11 women die from the disease.

Approximately 15.5 million Americans have a history of cancer.

Cancer deaths have decreased by 1.8% per year among men and by 1.4% per year among women in the last 16 years.

Over the past 25 years there has been a 27% drop in the overall US cancer death rate, translating into about 2.6 million fewer cancer deaths between 1991 and 2016.

Six biological capabilities of cancer include: sustained proliferative signaling, activation of local invasion and metastasis, induction of angiogenesis, evasion of growth suppressors, resistance to cell death, and unlimited replicative potential.

Cardiovascular diseases and cancer share a number of common risk factors such as tobacco smoking, lack of cardiorespiratory fitness, obesity, and diabetes.

Cells have 6 capabilities: self-sufficiency in growth signals, insensitivity to growth inhibition signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis and tissue invasion and metastasis.

Cancer can be thought of as a disturbance in the homeostatic balance between cell growth and cell death. 

Over-expression of anti-apoptotic genes, and under-expression of pro-apoptotic genes, can result in the lack of cell death that is characteristic of cancer. 

Normal cells become malignant cells through a succession of genomic alterations.

A heterogenous disease.

Cancer cells within a tumor or heterogeneous and may differ in morphology, genetics, cell surface markers, proliferation kinetics, tumorigenicity, and response to therapy.

Molecular information reveals cancers vary from one primary site to another.

Intertumor heterogeneity of each cancer type exists.

Cancer heterogeneity is not limited to differences between different patients but within a single patient.

Cancer heterogeneity occurs at the molecular, cellular, tissue and organ levels.

Intratumoral heterogeneneity provides the basis for classifying cancer types and subtypes by differences in histology, genetic profile, protein signatures, or expression of specific markers.

Intratumoral heterogeneneity complicates cancer prognosis and treatment.

There are multiple clonal populations within tumors.

It is estimated by immunohistochemical studies done at approximately 5% of cancer cells are heterogeneous.

Heterogeneous cells may be diffusely present, intermixed, or clustered.

Heterogeneity accounts for the results of treatment for metastatic disease with mixed response, such that patients with a mixed response due to heterogeneity have worse survivals.

NCI definition of survivorship as beginning on the day of diagnosis and continuing through the end of life.

Self reliance for cell growth by establishment of autocrine loops is one the mechanisms in oncogenic transformation.

A disease of the cellular genome.

The cancer genome relates to acquired mutations including several classes of DNA sequence changes from base substitutions to insertion or deletion of small or large fragments of DNA, rearrangements of DNA segments, copy number increases from two to many hundreds of copies, and copy number losses.

Cell cycle aberrations in cancer include activation of positive regulatory proteins such as cyclins, CDKs, or loss of negative regulatory proteins that include CDK inhibitor p16, the substrate retinoblastoma, and p53 family members.

Often arises because of normal signaling pathways are disrupted.

Cells sometime acquire mutations that cause growth to be dependent on a particular pathway or process allowing a growth advantage.

It is estimated 2/3 of cancer causing mutations result from random errors in replication.

Environmental causes account for 29%, and hereditary for 5% of cancer causing mutations.

Environmental causes account for 29%, and hereditary for 5% of cancer causing mutations.

Majority of lesions display aneuploidy, multiple genetic alterations and or genetic instability.

Constitutes abnormal uncoordinated cellular growth which persists after cessation of the initial transformational event.

Combinations of somatic or hereditary genetic ad epigenetic events constitute the basis for the instability required for neoplastic transformation.

At least 3% of all cancer cases are attributed to hereditary variation in cancer predisposition genes, and 5-20% of breast cancer or ovarian cancer cases are linked to genetic abnormalities.

Only when abnormalities occur in multiple genes does invasive cancer develop, so individual mutations contribute to rather than sole cause of cancer.

Overlap between type II diabetes and cancer has been explained by high levels of circulating insulin and insulin like growth factor 1, both of which are growth factors, that characterize insulin resistance states such as type II diabetes.

Regularly induce immunologic unresponsiveness or tolerance toward tumor related antigens.

Biologic, chemical and physical agents can initiate or promote neoplastic changes by causing genetic instability, somatic derangements to preneoplastic and tumor cells.

It is estimated that 20-25% of cancers are related to positive energy balance including overweight/obesity, poor nutritional status, and physical inactivity.

There is a rising incidence of deaths due to obesity related cancers.

Of the 13 cancers linked to obesity, eight have increased in incidence among younger patients, suggesting obesity accelerates development of some cancers and that is why they are showing up in younger people.

Excess body weight accounts for the second highest proportion of cancer cases and deaths attributable to potentially modifiable risk factors after cigarette smoking.

In 2014 it was found that 7.8% of all cancers, excluding nonmelanoma skin cancers, among adults 30 years and older were attributed to excess bodyweight, with a higher burden among women than men (Islami F).

Studies show that 10 to 40% cancer risk reduction in the most physically active study participants when compared to least active participants.

Cells rely on glycolysis (Warburg effect) even in the presence of oxygen.

The Warburg effect indicates the dependence of tumors on nonoxidative fermentation of sugar into lactic acidosis (glycolysis).

Cancer cells favor glycolysis for energy production over mitochondrial oxidative phosphorylation, even when oxygen supply ample. 

Cumulative evidence suggest chronic inflammation plays a role in the pathogenesis of cancer, especially colorectal cancer.

Chronic inflammation increases the risk of cancer associated demonstrated by inflammatory bowel disease, HIV, viral hepatitis B and C, human papilloma virus and rheumatoid arthritis all associated with increased risk of specific types of cancer.

DNA material may be incorporated into cancer cells from exogenous sources such as viruses as noted above.

Cancer cells accumulate mutations during their lifetime but only a few of these mutations are critical to initiate and to the progression of cancers while most play no significant role in the pathogenesis of cancer.

12 million new cases globally and 8 million deaths per year.

1.7 million new cases/year in United States, and 590,000 deaths.

In 2016 in the US, cancer is the second leading cause of death with 1.6 million new cancer cases and 0.6 million cancer deaths projected to occur.

Malignancy age-standardized mortality of 134.3 per hundred thousand.

Virus-associated malignancies account for 10-15% of human cancers worldwide.

Estimated 1.5 million cases per year, or 15% of all cases worldwide attributed to infectious etiologies, mostly related to virus infections.

Mortality rate has decreased from approximately 200 to 165 deaths per 100,000 population.

Almost 90% of cancer deaths are due to metastases.

The cancer mortality rate varies as much is 30% across US states and is strongly associated with state-level tobacco use.

Some DNA viruses associated with cancer include : hepadnaviruses, such as hepatitis B (hepatocellular carcinoma), herpesviruses such as Kaposi’s Sarcoma-associated herpesvirus (human herpesvirus-8), and Epstein-Barr virus (nasopharyngeal carcinoma, non-Hodgkin’s and Hodgkin’s lymphoma), polyomavirusessuch as Merkel cell virus (Merkel cell carcinoma) human papilloma virus (anogenital cancers and head and neck cancers).

Infectious diseases common cause of cancer, with 2 million cases annually worldwide.

Infectious agents associated with cancers include:Helicobacter pylori, hepatitis B, hepatitis C, Opisthorchis viverrini, CLonorchis sine sis, human papilloma virus, Epstein-Barr virus, human T-celllymphotropic virus type 1, human herpes virus type 8, and Schistosoma haematobium

Commonly lacks costimulatory molecules on tumor cells and tumor infiltrating antigen presenting cells (APCs).

One in four deaths in the U.S. is due to cancer.Causes over 8 million deaths worldwide annually.

Second leading cause of death worldwide behind cardiovascular disease.

Estimated 1,660,290 new cancer cases in the U.S. in 2013.

Incidence of new cancer cases in 2013 was 463 per 100,000 persons per year.

In 2009 an annual incidence rate of 524 cases per hundred thousand among men and 414 among women.

Cancer rates are highest, 473 per 100,000 population, among blacks and lowest among American Indian/Alaskan natives 273, primarily reflecting differences in rates of cancers of the prostate and female breast.

Approximately 564,000 Americans die annually of cancer in the U.S.

In 2009 an estimated 270,000 deaths among women and 293,000 deaths in men in the U.S.

54% of the incident cancers in the United States occur in those 65 years of age or older.

Leading cause of deaths in US Hispanics.

There is an increased risk of malignancy in patients with cardiovascular disease, including increase in patients with heart failure, heart failure after myocardial infarction, patients who have undergone cardiac intervention, and patients after thrombotic events.

Approximately 12,000,000 people with previous diagnosis of cancer are living in the US with cancer, and more than two thirds of individuals diagnosed with cancer expected to live 5 years after diagnosis.

Cancer survival divided into 3 phases: Acute phase from diagnosis until completion of initial treatment, the extended phase, the period of partial or complete remission after the initial treatment, and permanent survival phase, period of low likelihood of primary disease recurrence (Schaiova, L et al).

About 12.7 million cases and 7.6 million cancer deaths occurred in 2008 worldwide, with 56%, of the cases and 64% of the deaths in the economically developing world.

Cancer incidence for all cancers decreased 0.8% per year between 1990 and 1997.

Most common cause of death among the people under the age of 85 years in the United States.

Deaths from cancer on the decline and incresing number of survivors.

Leading cause of in economically developed countries and the second leading cause of death in developing countries.

The median age at diagnosis in the United States is 67 years and a median age at cancer death is 73 years.

Incidence of most malignancies increase as a fourth-fifth power of age.

Incidence projected to nearly double by 2020 as the population ages and grows in size.

Burden of cancer increasing as a result of population aging and growth as well as the adoption of cancer associated lifestyle choices including smoking, physical inactivity, and westernized diets.

Unmarried patients are at a greater risk for late-stage diagnosis, undertreatment, and cancer-related death, and effects are more pronounced in men than women.

Present in 160/100,000 males and 186/100,000 females worldwide, with variability in frequency between countries.

Central Cancer Registries have shown that on average, nearly 1% decline in new cases between 1999 and 2006 in the United States.

Death rates dropped in the US, 1.6% annually from 2001-2006, mainly due to reductions in new cases and death rates for the three most common cancers in men and for two of the three leading cancers in women.

Accounts for almost 7 million deaths annually worldwide.

Mortality has declined 15% since 1990.

Approximately 25% of new cancer diagnoses are in patients 65-74 years, approximately 22% in patients 75-84 years and about 7-1/2% in individuals 85 years of age or older (CD inC).

Today 2/3 of patients survive at least 5 years after diagnosis.

In 2006 it was estimated that 11,400,000 adults and children were living with cancer in the U.S.

In 2015, 14.5 million Americans living with the recent the remote history of cancer.

Projected 60% of cancer incidence and 70% of cancer related mortality occur in individuals 65 years of age or more.

Leading cause of death in the US for those under the age of 85 years and the second leading cause of death overall.

One in 2 men and women born today will be diagnosed with cancer during her lifetime.

It is believed that there are 5-6 rate limiting mutations necessary to cause cancer.

Models suggest that the first mutation alters phenotype, to make subsequent rate limiting mutations more likely.

When first degree relatives have cancer, there is generally 2-5 fold elevation in the likelihood of the development of cancer.

Global incidence 11 million with more than 7.6 million deaths in 2005.

A disease of the elderly with more than 60% of patients older than 65 years.

Age most important risk factor.

Median age at diagnosis is 67 years.

Over 56% of patients from SEER data are diagnosed in patients over the age of 65 years.

Up to age 40 years the probability of developing an invasive cancer is about 1% in men and 2% in women.

The probability of developing cancer for persons aged 60-79 years is 35% for men and 23% for women.

Most of the major tumors occur in greater proportion in men and women over the age of 65 years.

Lifetime probability of developing an invasive cancer is more than 40%.

Cancer burden increasing due to a growing age of population.

Survival in patients with less than 10% of loss of body weight is significantly longer than in patients with a greater weight loss.

5 years survival rates continue to increase from 50% in 1975-1997 up to 65.8% in 2003-2009.

8-18% of cancer patients have diabetes associated a comorbid illness.

Patients with recent diagnosis of cancer have increased risk of having suicide and death from cardiovascular disease (Fang F et al.

Anemia found in up to 75% of patients have mild to moderate anemia.

Incidence for all cancers decreased 0.8% per year between 1990 and 1997.

Trends from 1990-2002 reveal a decline in mortality rates of about 1% per year, with individuals aged 66-65 years and blacks showing the largest declines.

Greatest declines in mortality rates in the last decade are for breast and colorectal cancer in women and for prostate, lung and colorectal cancer in men.

Diagnosed at the same time or within one year after an episode of venous thromboembolism associated with an advanced stage of cancer and poor prognosis.

150 agents officially approved for treatment of cancer worldwide.

Most common epithelial cancers cause more than 75% of cancer deaths, remain incurable.

Among 1000 patients with advanced lesions the median number of symptoms was 11, with 84% experiencing pain (Gift).

Patients with advanced disease rarely have symptoms in isolation and most experience problems in clusters.

Survivors under the age of 19 years comprise 1% of the prevalent cancer population.

Estimated 15.5 million cancer survivors living in US today.

Young adults who have had cancer ages 20-39 years represent 5% of the cancer survivor population and survivors 40-59 years of age account for 24%.

Among cancer survivors two thirds will have survived more than 5 years beyond there diagnosis, and 2 of every 5 survivors will be considered a 10 year survivor.

Patients over the age of 60 represent 70% of the cancer survivor population.

Doll and Peto estimated that of the major known causes of cancer: Smoking accounted for 30% of cases, diet and lack of physical activity, 35%, and infections, 17%, with smaller fractions related to reproductive and sexual behavior, alcohol, medications, medical procedures, occupation, geophysical factors, and pollution.

5-6% of new cancers and deaths globally are directly linked to drinking alcohol.

Approximately 87,000 cancers each year in the US are associated with alcohol include cancers of the oral cavity, pharynx, larynx, liver, esophagus, female breast, and colorectal.

Countries that reduce their alcohol intake are associated with lower risk of cancer.

It is estimated that one third of the more than 572,000 cancer deaths that occur in the United States each year is attributed to diet and physical activity habits, including overweight and obesity, an another third is cause by exposure to tobacco products (American Institute for Cancer Research).

Estimated obesity and overweight contribute 14-20% of all cancer related mortality (Calle EE et al).

The link of Cancer by obesity is in part through deoxycholate. 

Occupational exposures account for an estimated 2 to 5% of cancers in the United States.

Approximately 30-40% of cancer incidents are preventable by the consumption of a healthy diet, regular exercise, maintenance of optimum weight and more than 20% by consuming more vegetables and fruits.

Exercise during and after treatment reduces cancer recurrence and disease specific mortality rates of 30% to 60% in breast and colon cancers.

Avoiding exposure to carcinogens, receiving vaccinations for oncogenic viruses, minimizing tobacco use and obesity it is possible to reduce cancer incidence by 50% or more.

Up to 60% of cancer patients use complementary and alternative medications to help improve clinical outcomes, controlling symptoms and enhancing quality of life.

Management of cancer is associated with its site of origin, histopathology subtype, and stage.