cause xeroderma pigmentosum are associated with neurodegeneration. xeroderma pigmentosum may be caused by genetic mutations in 8 genes, which produce the following enzymes: xpa, xpb, xpc, xpd, xpe, xpf, xpg and pol η. xpa-xpf are nucleotide excision repair enzymes that repair uv light-damaged dna and faulty proteins will allow the buildup of mutations caused by uv light. pol η is a polymerase, which is an enzyme involved in dna replication. there are many polymerases, but pol η is the enzyme that replicates uv light-damaged dna. mutations in this gene will produce a faulty pol η enzyme that cannot replicate dna with uv light damage. individuals with mutations of this gene have a subset of xp; xp-variant disease. dna repair defects and increased cancer risk many cancer syndromes are due to an inherited impairment in dna repair capability. when an inherited mutation is present in a dna repair gene, the repair gene will either not be expressed or expressed in an altered form. then the repair function will likely be deficient, and, as a consequence, dna damages will tend to accumulate. such dna damages can cause errors during dna synthesis leading to mutations, some of which may give rise to cancer. germ-line dna repair mutations that increase the risk of cancer are listed in the table. inherited dna repair gene mutations that increase cancer risk dna repair gene protein repair pathways affected* cancers with increased risk ataxia telangiectasia mutated atm different mutations in atm reduce hrr, ssa or nhej leukemia, lymphoma, breast bloom syndrome blm (helicase) hrr leukemia, lymphoma, colon, breast, skin, lung, auditory canal, tongue, esophagus, stomach, tonsil, larynx, uterus breast cancer 1 & 2 brca1 brca2 hrr of double strand breaks and daughter strand gaps breast, ovarian fanconi anemia genes fanca,b,c,d1,d2,e,f,g,i,j,l,m,n,o,p fanca etc. hrr and tls leukemia, liver tumors, solid tumors many areas hereditary nonpolyposis colorectal cancer genes msh2 msh6 mlh1 pms2 msh2 msh6 mlh1 pms2 mmr colorectal, endometrial, ovariain, gastrointestinal tract (stomach and small intestine, pancreas, biliary tract), urinary tract, brain (glioblastomas), and skin (keratoacanthomas and sebaceous adenomas) li-fraumeni syndrome gene tp53 p53 direct role in hrr, ber, ner and acts in dna damage response for those pathways and for nhej and mmr sarcomas, breast cancers, brain tumors, and adrenocortical carcinomas mre11a mre11 hrr and nhej breast mutyh mutyh glycosylase ber of a paired with 8-oxo-dg colorectal, duodenal, ovarian, bladder and skin cancers nijmegen breakage syndrome nbs (nbn) nhej lymphoid cancers nthl1 nthl1 ber for tg, fapyg, 5-hc, 5-hu in dsdna colon cancer, endometrial cancer, duodenal cancer, basal-cell carcinoma recql4 recq4 helicase likely active in hrr basal cell carcinoma, squamous cell carcinoma, intraepidermal carcinoma werner syndrome gene wrn werner syndrome atp-dependent helicase hrr, nhej, long patch ber soft tissue sarcoma, colorectal, skin, thyroid, pancreas xeroderma pigmentosum genes xpa, xpb, xpd, xpf, xpg xpa xpb xpd xpf xpg transcription coupled ner repairs the transcribed strands of transcriptionally active genes skin cancer (melanoma and non-melanoma) xeroderma pigmentosum genes xpc, xpe (ddb2) xpc, xpe global genomic ner, repairs damage in both transcribed and untranscribed dna skin cancer (melanoma and non-melanoma) xpv (also called polymerase h) dna polymerase eta (pol η) translesion synthesis (tls) skin cancers (basal cell, squamous cell, melanoma) the acronyms for dna repair pathways are hrr homologous recombinational repair, ssa sub-pathway of hrr, nhej non-homologous end joining, ber base excision repair, tls translesion synthesis, ner nucleotide excision repair, mmr mismatch repair. genetic screening genetic testing can be used to identify mutated genes or chromosomes that are passed through generations. people who test positive for having a genetic mutation are not necessarily condemned to develop the cancer linked with the mutation, however they possess an increased risk of developing cancer in comparison to the general population. it is advised that people get a genetic test if their family medical history includes: multiple family members with cancer, someone in their family that got cancer at a particularly young age or by being part of a certain ethnic group. an example of a direct to consumer genetic testing kit. this kit comes from the company 'mygene'. the process of genetic screening is a simple, non-invasive procedure. however, before genes are tested for mutations the patient usually must go to a health care provider and go through a one-on-one consultation, where they discuss both the personal and family history of cancer. the medical professional can then assess the likelihood of the patient having the mutation and can guide them through the process that is genetic screening. it is important that this consultation takes place because it ensures that the person gives informed consent to engage in genetic testing, is aware and understands the steps, benefits and limitations of the procedure and is more knowledgeable of the consequences of hearing test results. the test can be done by using body fluids or cells of the patient, this includes; blood (which is the most common), saliva, amniotic fluid and even cells from the interior of the mouth gotten from a buccal swab. this material is then sent to a specialized genetics lab where technicians will examine it, the test results are sent back to the health provider who requested the analysis and results are discussed with the patient. direct to consumer testing can be obtained without a medical professional but is not recommended as the consumer loses the opportunity to discuss their decision with an educated professional. according to the national library of medicine in the u.s. genetic testing in america costs in the price range of $100-$2000 depending on the type and intricacy of test. preventive actions genetic testing is important as if a test comes out positive they are more aware of their own personal health and the health of immediate family members. with the help and advice from a medical professional they can take steps to reduce their elevated risk of cancer development through: regular exercise a healthy, balanced diet maintaining a healthy weight not smoking staying safe under the sun's harmful rays there are other forms of preventive actions, an example for hereditary breast and ovarian cancer would be to go through surgery: a hysterectomy is the removal of all or some of the uterus, whereas a mastectomy is removing a breast (double mastectomy meaning that both breasts are removed), this can often add years onto their life expectancy. another preventive measure is regular cancer screening and check-ups. if a person has lynch's syndrome then they should have a regular colonoscopy to examine if there is any change in the cells lining the intestinal wall, regular check-ups are associated with an additional 7 years onto the life expectancy on average for a person with lynch's syndrome. this is because early detection means the correct preventive actions and surgery can be taken quicker. regular breast screening is also recommended for women diagnosed with brca mutations, as well as that, recent studies show that men with increased risks of developing prostate cancer due to brca mutations can decrease their risk by taking aspirin. aspirin is hugely beneficial in lowering cancer prevalence; however, it must be taken regularly over at least a five-year period to have any effect. prevalence of genetic mutations in different ethnic groups often genetic mutations are more common in certain ethnic groups, this is because a race can track their ancestors back to one geographic location, the mutated genes are then passed from ancestors down through generations which is why some ethnicities are more susceptible to mutations, thus increasing their chances of developing cancer . as mentioned above, this can be useful as it can help health professionals assess a patient's risk of having a mutation before they undergo testing. werner's syndrome has a prevalence of 1 in 200,000 live births in the u.s., but it affects individuals in japan in 1 in 20,000-40,000 cases. 1 in 40 ashkenazi jews have a brca mutation, this is a huge contrast from the general population in the united states where 1 in 400 people are affected. ashkenazi jews are at high risk of developing hereditary breast and ovarian cancer and it is recommend that they undergo both genetic testing to see if they have a mutation and regular screening for cancer.