Both genetic and environmental factors have been implicated in the mechanism of Causes for trends in breast cancer incidence are not fully understood. Information about biological processes of cancer – e.g. genetic one of the three following groups of environmental carcinogens: chemical mutagens, . Approximate correlation of early genetic events in the development of. Research indicates that genes react to environmental cues by way of several different mechanisms. Chemical mutagens alter the delicate chemistry of the base pairs that Interestingly, DNA repair pathway genes are often mutated in cancers and . Discovering the Relationship Between DNA and Protein Production.
It is interesting to note that germ line mutations of activated oncogenes are normally not inherited. They may arise during gametogenesis, but the mutant alleles are typically dominant at the cellular level, which results in disturbance of normal embryonic development, and reduced viability of these embryos. Fortunately, the inherited cancer predisposition syndromes listed in Tables 2 and 4 are extremely rare diseases, but they represent powerful illustrations for the importance of DNA repair and tumour suppressor genes for maintaining body homeostasis.
Principal applications of genetic testing in cancer As an increasing number of cancer-related genes or gene mutations is characterised, the potential of DNA and RNA expression testing for cancer-related applications is being explored.
Cancer biology: Molecular and genetic basis - Oncology for Medical Students
Gene mutation screening in families with inherited cancer predisposition syndromes, which identifies at- risk individuals in such families and allows for decisions to be made about early disease monitoring, aggressive treatment regimens and prophylactic surgery e.
Gene expression microarray analysis can be used for classification of cancer subtypes, e. Other applications include the diagnosis of benign vs. Tumour cells may be recognised by the immune system through the expression of tumour-associated antigens, but the antigenicity varies considerably between different types of antigens.
In order to avoid an attack by the immune system, tumour cells use a range of strategies, such as suppression of expression of tumour-associated antigens or of MHC class 1 molecules, or even counterattack against immune cells.
The Influence of Environmental and Genetic Factors on Various Disorders and Diseases
Research into immunotherapy of cancers aims to devise novel strategies to support the anti-cancer immune response; principal approaches include: Antigen-independent cytokine therapy e. Novel approaches arising from cancer cell biology The progress in our knowledge about gene mutations frequently occurring in cancers, combined with the development of modern molecular biology methods has led to both new diagnostic tools see Principal applications of genetic testing in cancer and new treatment modalities that have shown some success in the management of selected types of cancers.
The knowledge about cancer—associated genes and their role in cellular growth signalling pathways has led to the development of a considerable number of anti-cancer drugs targeting such signalling pathways: Two examples of such successful anti-cancer agents are the monoclonal antibody Herceptin for the treatment of a specific subtype of breast cancer, and the small-molecule inhibitor Gleevec targeting the fusion protein Bcr-abl, a mutant tyrosine kinase, involved in the development of chronic myeloic leukaemia CML.
A third group of potential drug targets are some anti-apoptotic proteins that are frequently overexpressed in cancer cells. Targets of novel anti-cancer drugs in cellular growth signalling pathways. The cell membrane is indicated in light grey, red diamonds represent growth factors, green shows the growth factor receptor with the intracellular tyrosine kinase domain Tk indicated by the red circle.
Coloured rectangles symbolise signalling components belonging to specific pathways Blue: Dotted black arrows point to cell biological outcomes of these pathways. Groups of novel anticancer drugs and their targets are shown in red. The biology of cancer. Garland Science,  Back to top Summary: A summary of the 6 hallmarks of cancer.
Genetics of Cancer
Additional capabilities crucial to cancer phenotypes that are not shown here include defects in DNA repair mechanisms and signalling interactions of the tumour microenvironment.
Hanahan D, Weinberg RA. Cell,  Self-sufficiency in growth signals: Tumours have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation. Insensitivity to growth-inhibitory signals: Tumour cells may not respond to molecules that are inhibitory to the proliferation of normal cells.
Tumours may be resistant to programmed cell death, as a consequence of inactivation of p53 or overexpression of anti-apoptotic proteins. Defects in DNA repair: Tumours may fail to repair DNA damage caused by carcinogens or unregulated cellular proliferation. Tumour cells have unrestricted proliferative capacity, associated with maintenance of telomere length and function.
This prospective, non-randomized study assessed toxicity and potential efficacy of low-dose granulocyte macrophage colony-stimulating factor GM-CSFinterferon alpha IFN and interleukin 2 IL-2 postoperatively in patients with highrisk renal cell carcinoma RCC [ 22 ]. Prostate cancer PC is the second leading cause of cancer deaths in men in America and Western Europe.
Epidemiological studies suggest that prostate cancer incidence increased in last few years in Asian population [ 23 ]. Liposomes are recognized as important vehicles for cytotoxic drugs because they can protect the drugs from degradation in circulation, thereby protecting healthy cells and tissues from exposure to lethal drug doses [ 24 ].
In the aetiology of HIV-1 infection, some genetic factors may be important, for example the gene variants, which encode chemokine receptors: This finding might be useful for epidemiological researches of HIV infections and other diseases like diabetes [ 25 ].
Asthma and chronic obstructive pulmonary disease COPD show similarities and substantial differences. It is stipulated that asthma and COPD have common genetic and environmental risk factors, which ultimately lead to clinical disease depending on the timing and type of environmental exposures.
Thus, a particular group of shared genetic factors may lead to asthma when combined with specific environmental factors, whereas combination with other environmental factors, will lead toward COPD.
The genetic predisposition to certain pathways may further help to define the development of either asthma or COPD. In the end this may lead to stratification of patients by their genetic make-up and open new therapeutic prospects [ 26 ]. Metabolic syndrome is defined as a cluster of multiple risk factors, including central obesity, dyslipidemia, hypertension and impaired glucose tolerance, that increase cardiovascular disease morbidity and mortality. Genetic factors are important in the development of metabolic syndrome, as are environmental factors [ 28 ].
Ovarian cancer is the fourth leading cause of cancer-related death in women in the U. Specifically, epithelial ovarian cancer EOC is characterized by few early symptoms, presentation at an advanced stage, and poor survival.
There are more thannew cases of epithelial ovarian cancer EOC each year worldwide and this malignancy represents the leading cause of death from gynecological cancers. The possibility of using ANXA7 as both a clinically relevant indicator of disease progression and a prognostic biomarker for survival in the patients with ovarian cancer [ 29 ]. Chronic infantile neurological cutaneous and articular syndrome CINCAalso known as neonatal-onset multisystem inflammatory disease NOMIDis dominantly-inherited systemic auto inflammatory disease.
Some Neuroendocrine tumours NET occur in hereditary-familial neoplastic syndromes such as MEN multiple endocrine neoplasias or neuroectodermic dysplasias neurofibromatosis-NF1, von Hippel Lindau disease, pheochromocytoma-chemodectoma familial syndrome, etc. HNF1B nephropathy is typically responsible for bilateral renal cystic hypodysplasia in childhood One findings have provided data that are useful for recognition and diagnosis of HNF1B disease in adulthood and might help in renal management and genetic counseling [ 31 ].
Genetic defects of platelet function give rise to mucocutaneous bleeding of varying severity because platelets fail to fulfil their haemostatic role after vessel injury [ 32 ]. Mendelian inheritance has been demonstrated for some disorders, others are associated with mutations and polymorphisms in susceptibility genes [ 33 ].
If stable gene transfer is desired, non-integrating vector systems may be combined with transposon-or phage integrase-based systems or future site-specific systems to achieve integration into the host B cell genome [ 34 ]. First time a de novo chromosomal abnormality which produced the phenotype of a female with primary ovarian failure and subsequent osteopenia in early adult life [ 35 ]. Mutations in several multidrug resistance proteins MRPs are associated with human genetic disorders [ 36 ].
Dravet syndrome, also called severe myoclonic epilepsy of infancy SMEIis a severe form of epilepsy. It appears during the first year of life with frequent febrile seizures — fever-related seizures.
- Environmental Factors Inducing Human Cancers
- Cancer biology: Molecular and genetic basis
Dravet syndrome depends on a series of independent factors including seizure control, behavior, cognitive, and motor problems [ 37 ]. FA is a model disease in cancer research, yet there are no contemporary data on carrier frequency or prevalence in the general United States US population or elsewhere [ 38 ]. Genetic, hormonal and life-style related factors determine SHBG levels and low sex hormone-binding globulin levels are a known risk factor for the development of the metabolic syndrome, diabetes and cardiovascular diseases [ 39 ].
Environmental factors influencing diseases in different ways During the past few years, experimental evidence has emerged to suggest that environmental factors may influence cellular proliferation attrition in an organ-specific manner. Mostly, transmission rates were significantly lower than expected. Traditional risk factors for breast cancer explain only a fraction of cases. Causes for trends in breast cancer incidence are not fully understood.
Breast cancer incidence and mortality rates decrease with environmental conditions that promote Vitamin D synthesis in human skin including lower latitude and higher personal exposure to sunlight [ 34 ].
Environmental factors are threats to health, and controlling them is public environmental health. They include [ 41 ]. Genetic Disorders in Humans. Just few years ago, retrovirus integration was believed to be random and the chance of accidentally activating a gene was considered remote. Tumorigenesis associated to some studies in gene therapy is suspected to be caused by insertion process. Depending on whether the provirus integrates into or in the vicinity of genes normal trascription can be enhanced or disrupted thus inducing oncogenic mutations.
Investigating whether an area over the genome could be favoured by retrovirus integration is a crucial aspect in gene therapy. Recombinant adeno-associated virus rAAV -based gene therapy represents a promising approach for the treatment of heart muscle diseases, but the molecular mechanisms that direct rAAV transduction remain unclear. It is concluded that a calcium-dependent pathway regulates rAAV vector transduction at a number of stages that may include vector mobilization, conversion, and transcription activity.
Liposomes are recognized as important vehicles for cytotoxic drugs because they can protect the drugs from degradation in circulation, thereby protecting healthy cells and tissues from exposure to lethal drug doses. Liposomes have been touted as tumor-specific and effective carriers of cytotoxic drugs. However, they are not devoid of significant problems including premature destruction to cause toxicity to healthy tissues or in the other extreme, undesirably long stability to prevent effective delivery to the tumor cells [ 44 ].
Plasma B-type natriuretic peptide BNP values have been evaluated as predictors of outcome and are helpful in determination of therapeutic options in patients with both acute and chronic heart failure [ 45 ]. Early and increased amounts of plasma have been associated with improved survival after penetrating and blunt injury.
However, no studies involving burn patients demonstrate the effects of Intraoperative plasma administration on postoperative resuscitation requirements. Malignant tumors or cancer are always serious and will often lead to death if not treated promptly.
Malignant tumors often spread or metastasize to other organs. The steps involved in the formation of colon cancer or rectal cancer are shown.Genetics and the Environment in Cancer Risk -- Sloan-Kettering
In the first drawing labeled "normal"note that each of the normal cells are about the same size, are organized in a orderly fashion, and are all on top of a basement membrane. A basement membrane separates these cells from other types of cells and from cells of different organs of the body.
At some time, a normal cell develops enough mutations that it begins to grow slightly faster than the cells around it the reddish cell in the center of the second drawing, labeled "single hyperproliferative cell". Hyperproliferative means the cell grows faster than normal cells.
When enough hyperproliferative cells accumulate, a small benign tumor called an adenoma develops third drawing. During a colonoscopy, the doctor is looking for such adenomas. If an adenoma is removed at this stage, the patient will be fine and a cancer will not develop from this particular group of cells. Note two things about the adenoma in the third drawing: If the adenoma is allowed to remain in the patient for many years, a cancerous tumor called a carcinoma will form inside of the adenoma.
The cells in this carcinoma break through the basement membrane and will spread inside the colon, eventually leaving the colon to spread to other organs like the liver.
In the fourth drawing, a tumor cell can be seen in the lower right hand corner breaking into a small blood vessel pink segmented circle. Cancer cells often use body fluids like the bloodstream to spread or metastasize. Ultimately, it is this lack of respect for the body by cancer cells that dooms a person to death.
To return to our example of liver cancer, the cancerous liver cells do not perform the job of the liver and destroy the normal liver cells around them by their lack of respect for those cells. In the end, the person is left without a functional liver and dies of liver failure.
Cancer is many different diseases. Cancer is not one disease,but literally hundreds of different diseases. This is of great practical importance to both physicians and patients, because different cancers are treated differently and have different outcomes for the patient.
For instance, breast cancer is different from brain cancer: If caught early, breast cancer is a very treatable disease, and patients can look forward to a cure and a normal life expectancy. On the other hand, brain cancer is an extremely aggressive disease, and the outcome is usually poor, regardless of how early the cancer is detected.
Furthermore, brain cancer itself is not one disease but many diseases, each with different potential outcomes and treatments. In fact, if not caught early, breast cancer very often spreads metastasizes to the brain, and the breast tumor grows in the brain. Ultimately, for a typically non-aggressive disease like breast cancer, it is the spread of the tumor to a vital organ like the brain that causes illness and death.
Cancer is a genetic disease. Cancer is a genetic disease, and this should not be confused with the statement that cancer is a hereditary disease. The two statements are profoundly different. A hereditary disease is one that is passed from the parents to a child through the inheritance of a defective gene.
Although in some rare instances, such as retinoblastoma a rare childhood tumor of the eyecancer is hereditary, this is the exception rather than the rule.
Most cancers are not obviously hereditary, although for certain cancers, like breast cancer, there may be a hereditary component to the disease a "susceptibility". However, all cancers are genetic, meaning that they result from the unnatural function of one or more genes. Cancer forms when genes within a normal cell are damaged and mutated. Mutations in DNA can occur for many reasons. Cigarette smoke contains chemicals that will damage DNA. In most instances, the DNA damage will not lead to cancer or other diseases, but in some cases the damaged DNA does lead to cancer.
There are about 25, genes in each human cell, but, in most cases, a mutation within a gene will not lead to the development of cancer. It is only when mutations occur in certain key genes that cancer develops.