Cancer

• if a mutation occurs in a gene that controls cell division it can cause cancer

  this is bc the genes that control cell division don't behave as they should, which can result in uncontrolled cell growth
• mutations that occur in individual cells after fertilisation e.g. in adulthood are called acquired mutations:

  • if these mutations occur in the genes that control the rate of cell division (by mitosis), it can cause uncontrolled cell division
  • if a cell divides uncontrollably the result is a tumour
• a tumour is a mass of abnormal cells. tumours that invade and destroy surrounding tissue are called cancers
• there are 2 types of gene that control cell division - tumour supressor genes and proto-onco genes - mutations in these genes can cause cancer
• Tumour suppressor genes:

  • when functioning normally, tumour suppressor genes slow cell division by producing proteins that stop cells dividing or cause them to self-destruct (apoptosis)
  • if a mutation occurs in a tumour suppressor gene, the gene will be inactivated
  • the protein it codes for isn't produced and the cells divide uncontrollably (the rate of division increases) resulting in a tumour
• Proto-oncogenes:

  • when functioning normally, proto-oncogenes stimulate cell division by producing proteins that make cells divide
  • if a mutation occurs in a proto-oncogene, the gene can become overactive
  • this stimulates the cells to divide uncontrollably (the rate of division increases) resulting in a tumour
  • a mutated proto-oncogene is called an oncogene
• apoptosis is a type of programmed cell death - where cells that are infected, damaged or have reached the end of their functional life are destroyed
• mutations in tumour suppressor genes and proto-oncogenes are often acquired but some are inherited
• tumours can develop for years without any obvious symptoms and can be quite large by the time they are discovered
• not all tumours are cancerous - there are 2 types:

  • malignant
  • benign
• malignant:

  • cancers
  • usually grow rapidly and invade and destroy surrounding tissues
  • cells can break off the tumours and spread to other parts of the body in the bloodstream or lymphatic system
• benign:

  • not cancerous
  • usually grow slower than malignant tumours and are often covered in fibrous tissue that stops cells invading other tissues
  • often harmless
  • can cause blockages and put pressure on organs
  • some can become malignant
• the lymphatic system is a network of tubes which transports excess tissue fluid back into the circulatory system
• tumour cells: - can differ from normal cells in many different ways:

  • nucleus is larger and darker than in normal cells - sometimes the cells have more than one nucleus
  • have an irregular shape
  • don't produce all the proteins needed to function correctly
  • have different antigens on their surface
  • don't respond to growth regulating processes
  • divide by mitosis more frequently than normal cells
• causes of tumour growth:

  • no. of different factors thought to lead to the growth of tumours:
  • abnormal methylation of DNA
  • increased exposure to oestrogen
• abnormal methylation:

  • methylation means adding a mthyl group onto something
  • methylation of DNA is an important method of regulating gene expression - it can control whether or not a gene is transcribed (copied into mRNA) and translated (turned into a protein)
  • when methylation is happening normally, it plays a key role in many processes in the body
  • only when its happens too much (hypermethylation) or too little (hypomethylation) that it becomes a problem
• example:

  • when tumour suppressor genes are hypermethylated, the genes are not transcribed
  • so the proteins they produce to slow cell division aren't made
  • this means that cells are able to divide uncontrollably by mitosis and tumours can develop
• • hypomethylation of proto-oncogenes causes than to act as oncogenes
  • increasing the production of the proteins that encourage cell division
  • this stimulates cells to divide uncontrollably, which causes the formation of tumours
• Role of oestrogen in breast cancer:

  • some women may be exposed to more oestrogen than others
  • increased exposure may be the result of starting menstruation earlier than usual
  • starting menopause later than usual
  • taking oestrogen-containing drugs such as HRT
• increased exposure over an extended period of time is thought to increase a woman's risk of developing breast cancer

  exact reasons behind this are not fully understood - some theories as to how oestrogen can contribute to development of some breast cancers
• theories:

  • oestrogen can stimulate certain breast cells to divide and replicate - fact that there ae more cell divisions taking place naturally increases the chance of mutations occurring, and so increases the chance of cells becoming cancerous
  • oestrogens ability to stimulate division could also mean that if cells do become cancerous, their rapid replication could be further assissted by oestrogen, helping tumours to form quickly
• • other research suggests that oestrogen is actually able to introduce mutations directly into the DNA of certain breast cells, again increasing the chance of these cells becoming cancerous
• HRT stands for hormone replacement therapy - used to increase oestrogen and usually progesterone levels in some women in order to treat symptoms experienced during the menopause (end of menstruation)
• risk factors for cancer:

  • no single cause for cancer but scientists have identified lots of different 'risk factors' - things that increase a person's chance of getting cancer
  • can be environmental or genetic
• genetic factors:

  • some cancers are linked with specific inherited alleles (version of a gene)
  • if you inherit that allele - more likely to get that type of cancer
  • doesn't mean definitely will
  • e.g. hereditary mutations of the gene BRCA1 can greatly increase the chance of a women developing breast cancer in her lifetime
• environmental factors:

  • exposure to radiation
  • lifestyle choices such as
  • smoking
  • increased alcohol consumption
  • high-fat diet all been linked to increased chance of developing some cancer
• data on variation (the differences that exist between individuals) can be difficult to interpret bc some characteristics can be affected by many different genes (polygenic) and many environmental factors

  difficult to know which factors - genes or environment - are having the greatest effect - makes it hard to draw conclusions about the cause of variation
• a hereditary mutation in the BRCA1 gene might significantly increase your chances of developing breast cancer - doesn't mean you definitely will
• cancer is caused by mutations in proto-oncogenes and tumour suppressor genes

  understanding the role that these genes play in causing cancer and knowing exactly how they work can be really helpful for coming up with ways to prevent, treat and cure cancer
• Preventing cancer:

  • if a specific cancer-causing mutation is known, then it is possible to screen for the mutation in a person's DNA
  • e.g. it is possible to screen for the mutated allele of BRCA1 (tumour suppressor gene which greatly increases a woman's risk of developing breast cancer in lifetime)
• • knowing about this increased risk means that preventative steps can be taken to reduce it
  • e.g. a woman with the BRCA1 mutation may choose to have a mastectomy (removal of one or both breasts) to significantly reduce the risk of breast cancer developing
  • women with this mutation may also be screened for signs of breast cancer more often than the rest of the population, as early diagnosis increases the chances of recovery
• • knowing about specific mutations also means that more sensitive tests can be developed, which can lead to earlier and more accurate diagnosis
  • e.g. there is a mutation in the RAS proto-oncogene in around half of all bowel cancers - can be detected early by looking for RAS mutations in the DNA of bowel cells
• • people with a mutated APC tumour suppressor gene have frequent colonoscopies to diagnose hereditary colon cancer earlier
• treating and curing cancer:

  • the treatment for cancer can be different for different mutations
  • so knowing how specific mutations actually cause cancer can be useful for developing drugs to effectively target them
• • skin cancer caused by a mutation in the B-RAF proto-onco gene can be treated with the drug ZELBORAF
  • ZELBORAF inhibits the mutated B-RAF enzyme - this stops cells that express the mutation from growing
  • skin cancers caused by other mutations can't be treated this way
• • breast cancer caused by a mutation of the HER2 proto-oncogene can be treated with a drug called Herceptin
  • this drug binds specifically to the altered HER2 protein receptor and suppresses cell division and tumour growth
  • breast cancer caused by other mutations is not treated with this drug as it doesn't work
• • research is being conducted into treatment for breast, pancreatic and cervical cancers caused a faulty BRCA tumour suppressor gene
  • this involves using small molecules which block an enzyme involved in repairing DNA
  • the molecules may be able to prevent the DNA repair in cancerous cells containing a faulty BRCA gene
  • this kills the cancer cells and so could provide a targeted treatment for cancers caused by BRCA mutations
• it is very rare that such an extreme measure like removing a breast is taken - but a mutation in BRCA1 gives an extremely high 50-65% chance of breast cancer developing
• • some cancer-causing mutations require more aggressive treatments than others so understanding how the mutation that causes them works can help produce the best treatment plan
  • e.g. if a mutation is known to cause an aggressive (fast-growing) cancer, it may be treated with higher doses of radiotherapy or by removing larger areas of the tumour and surrounding tissue during surgery
• • gene therapy (where faulty alleles in a person's cells are replaced by working versions of those alleles may also be able to treat cancer caused by some mutations
  • e.g. if you know that the cancer is being caused by inactivated tumour suppressor genes, it's hoped that gene therapy could be used in the future to provide working versions of the genes