Inherited human DNA repair gene mutations that increase cancer risk

Individuals with an inherited impairment in DNA repair capability are often at increased risk of cancer. If there is a mutation in a DNA repair gene, the repair gene will either not be expressed or expressed in a mutated form, then the repair function will be deficient or altered, and damages will accumulate. Such DNA damages, if not repaired, cause errors during DNA synthesis leading to mutations that can give rise to cancer. This list shows the abbreviated names of the most well studied DNA repair genes for which a mutation results in an increased risk of cancer. The abbreviated names are followed by an abbreviated name of the repair pathway affected and by the tissue in which cancer develops when the gene is mutated. At the end of the list are shown the full names of the genes and the full names of the affected pathways.
*BRCA1, BRCA2
**HRR of double-strand breaks and daughter strand gaps
***Breast, ovarian
*ATM
**Different mutations reduce HRR, single strand annealing (SSA), NHEJ or homology-directed DSBR (HDR)
***Leukemia, lymphoma and breast cancer
*NBS
**NHEJ
***Lymphoid malignancies
*MRE11
**HRR
***Breast
*BLM
**HRR
***Leukemia, lymphoma, colon, breast, skin, auditory canal, tongue, esophagus, stomach, tonsil, larynx, lung and uterus.
*WRN
**HRR and NHEJ as well as long-patch BER
*** soft tissue sarcomas have a particularly high incidence in WS, but also colorectal, skin, thyroid, and pancreatic cancers
*RECQ4 (RECQL4) causing Rothmund-Thomson syndrome (RTS), RAPADILINO syndrome or Baller Gerold syndrome
**likely HRR
***cutaneous carcinomas, including basal cell carcinoma, squamous cell carcinoma, and Bowen's disease (intraepidermal carcinoma characterized by the development of pink or brown papules and sarcomas are the second most frequently reported malignancy, at a frequency of 9% of RTS cases.
*FANCA, FANCB, FANCC, FANCDl, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN
**HRR and TLS
***leukemia, liver tumors, solid tumors in many locations
*XPC, XPE(DDB2)
**NER(GGR type)
***skin cancer (melanoma and non-melanoma)
*XPA, XPB, XPD, XPF, XPG
**NER (both GGR type and TCR type)
*** skin cancer (melanoma and non-melanoma) and central nervous system
*XPV(POLH)
**TLS
*** skin cancer (melanoma and non-melanoma)
*hMSH2, hMSH6, hMLH1, hPMS2
**MMR
***colorectal, endometrial and ovarian cancer
*MUTYH
**BER of A mispaired with 8OH-dG, as well as mispairs with G, FapydG and C
***colon cancer
Names of genes: BRCAl, BRCA2 breast Cancer 1 and 2; ATM Ataxia telangiectasia mutated; NBS Nijmegen breakage syndrome; MRE11 meiotic recombination 11; BLM Bloom's syndrome; WRN Werner syndrome; RECQ4 (RECQL4) ATP-dependent DNA helicase Q4; FANCA, FANCB, FANCC, FANCDl, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN mutations in any of these 13 genes give rise to Fanconi anemia; XPC xeroderma pigmentosa C; XPE(DDB2) DNA damage-binding protein 2, the smaller subunit of a heterodimeric protein implicated in the etiology of xeroderma pigmentosum group E; XPA, XPB, XPD, XPF, XPG mutations in any of these 4 genes give rise to xeroderma pigmentosa; XPV(POLH) mutation in polymerase H gives rise to xeroderma pigmentosa; hMSH2, hMSH6, hMLH1, hPMS2 mutS (E. coli) homolog 2, mutS (E. coli) homolog 6, mutL (E. coli) homolog 1, postmeiotic segregation increased 2 (S. cerevisiae); MUTYH MutY homolog (E. coli).
Names of DNA repair pathways: HRR homologous recombinational repair; NHEJ non-homologous end joining; DSBR (HDR) double strand break repair (homology directed repair); TLS trans lesion synthesis; NER(GGR type) nucleotide excision repair (global genome repair type); NER(TCR type) nucleotide excision repair (transcription coupled repair type); MMR mismatch repair; BER of A base excision repair of adenine (mispaired).

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