1.1 Epidemiology of basal cell carcinoma
Incidence of basal cell carcinoma[edit source]
The incidence of basal cell carcinoma (BCC) is higher than that of any other cancer, though precise rates are unknown because generally BCCs are not registered and estimates from other sources are not current. The last national non-melanoma skin cancer survey, conducted in 2002, found the age-standardised annual incidence rate for BCC was 884 per 100,000, and was higher in men (1041 per 100,000) than in women (745 per 100,000). The survey also showed a strong inverse association with latitude, with the highest incidence in northern Australia, confirming collective observations from various local population-based surveys. For example, in Townsville, northern Queensland, age-standardised annual BCC incidence rates per 100,000 were 2058 for men and 1195 for women in 1997, similar to corresponding rates of 2074 and 1579 per 100,000 in Nambour, south-eastern Queensland, in 1992, but much higher than the estimated annual rate of 672 per 100,000 in Maryborough, Victoria, in the 1980s.
More recent estimates of BCC incidence for Australia (2011–2014) were based on data from a 10% random sample of Medicare administrative claims, examining item codes for excision of keratinocyte cancers (KCs), together with age- and sex-specific ratios of cutaneous squamous cell carcinoma (cSCC) to BCC from a population-based cohort. Annual incidence of BCC was estimated to be 770 per 100,000 (656 per 100,000 in women and 899 per 100,000 in men). Consistent with the 2002 survey, an inverse latitude gradient was observed, with the highest rates in Queensland (1355 per 100,000) and the lowest in Tasmania and Victoria (482 per 100,000).
These incidence rates are based on the number of persons affected per year; when the incidence of lesions is considered, the rates are considerably higher. For example, a 1992 survey conducted in Geraldton, Western Australia, reported annual BCC tumour incidence rates of 7000 and 3380 per 100,000 in men and women respectively, reflecting the high risk of multiple BCCs in those affected.
Incidence of BCC rises with age, but not linearly. In Australia, incidence in men is higher than in women up to approximately age 50 years, but similar at older ages.
In both sexes, over 50% of BCCs occur on the head or neck (mostly the face, especially eyelid, lip and nasolabial fold, followed by ears, nose and cheek), approximately 25% on the trunk and approximately 10% each on the upper and lower limbs.
The mortality rate of BCC is very low, at 1.9 deaths per 100,000 person–years at risk (total population).
Host factors[edit source]
Phenotypic factors that have been consistently and independently associated with increased risks of BCC include light skin that burns and does not tan (approximately 2-fold increase), propensity to freckling (approximately 2-fold increase), red hair (approximately 2-fold increase) and blue eyes (approximately 1.5-fold increase).
Prospective cohort studies have demonstrated that people who have photodamaged skin also have increased risks of BCC. Signs of photodamage associated with increased risk include the presence of actinic keratosis (greater than 3-fold increase), telangiectasia (greater than 3-fold increase), solar lentigines (approximately 3-fold increase), and elastosis of the skin of the neck (approximately 2-fold increase).
Environmental factors[edit source]
The substantial epidemiological evidence that ultraviolet (UV) radiation is the principal environmental cause of BCC is complemented by evidence from sequencing studies of BCC genomes. These studies have demonstrated exceedingly high burdens of genomic damage in BCC tumour DNA, mostly due to characteristic ‘signature mutations’, which are incurred specifically through UV-induced photolesions.
Despite the strong association with UV radiation, the dose–response relationship shows no direct correlation between total cumulative dose and risk of BCC. For example, a large, prospective study reported no association between occupational UV radiation exposure and risk of BCC. This finding mirrors those of the prospective Nambour Skin Cancer Study, which also found that BCC rates in outdoor workers were not significantly higher than rates among indoor workers. However, there was evidence of self-selection bias, whereby people with sun-sensitive phenotypes were grossly under-represented among outdoor occupations.
A meta-analysis of 24 studies found increased risks of BCC with outdoor work (summary odds ratio [OR] 1.43, 95% confidence interval [CI] 1.23–1.66), but observed significant heterogeneity by latitude, where studies conducted in countries with high levels of ambient UV radiation had less marked associations with outdoor work than studies conducted in high-latitude countries. However, early life sun exposure appears important, consistent with the observation that BCC is relatively common in younger age groups as well as older age groups.
Patterns of exposure may also be important. High-quality prospective studies have shown strong associations with numbers of sunburns, especially with sunburns occurring in early or middle life.
Artificial UV radiation[edit source]
Artificial tanning devices emitting UV radiation across wavelengths in the mutagenic spectrum are used for cosmetic purposes, especially by young women. The International Agency for Research on Cancer Working Group has classified such devices as ‘carcinogenic to humans’ (Group 1 carcinogen). Evidence that exposure to tanning devices increases the risk of BCC comes largely from case-control studies showing up to 2-fold higher risks of BCC among ever users compared with never users. Although commercial tanning devices were banned in Australia by 1 January 2016, many Australians have previously been exposed to commercial solariums and individuals can still use tanning devices privately.
Medical sources of exposure to artificial UV radiation include psoralen and ultraviolet A (PUVA), which was used in the past to treat psoriasis, and narrowband UVB, which superseded PUVA. In a US long-term prospective follow-up study with mean age 44 years at enrolment, patients who first received PUVA therapy in the mid-1970s had higher BCC rates than the general US population.
Other sources of radiation[edit source]
Inorganic arsenic is found naturally in soil or rock, where it can enter surface and groundwater. In previous eras, it was used for the treatment of many diseases, from anaemia to syphilis. Its association with skin cancer has long been known. Follow-up studies showed high rates of BCC among people in Queensland exposed to trivalent inorganic arsenic early in life through ingestion of an asthma medicine manufactured during the 1950s.
High levels of arsenic have been found in contaminated drinking water supplies in many countries, and these have been associated with high rates of BCC. The Australian drinking water guidelines recommend that arsenic concentrations in drinking water should not exceed 10µg/L. Values observed in Australia typically range from less than 5µg/L to 15µg/L. While data are sparse, US studies have found no evidence that low-level arsenic in drinking water is associated with BCC risk.
Two large meta-analyses conducted in 2012 reported inverse associations between smoking and BCC. Subsequently, three large prospective cohort studies have also reported inverse associations between smoking and BCC. On investigation, however, the observed decrease in BCC risk among smokers appeared to be a secondary (non-causal) association reflecting low BCC detection rates among current smokers, compared with non-smokers, due to the fact that smokers are less likely to undergo physician-led skin examinations and have asymptomatic BCCs diagnosed.
Numerous studies have examined the association between alcohol consumption and risk of BCC, with mixed results.
A meta-analysis combining various prospective and case-control studies found a significant dose–response relationship between alcohol and BCC (summary RR 1.07, 95% CI 1.04–1.09). However, a well-characterised Australian skin cancer cohort study observed no association between total alcohol intake and BCC risk, or any associations with specific classes of alcoholic beverages.
In summary, it is unlikely that a strong causal association exists, although modest contributory effects of alcohol to BCC risk cannot be discounted.
Two comprehensive reviews published in in 2005 and 2010 found no consistent evidence that BCC risk is influenced by dietary intakes or serum levels of retinol (vitamin A), carotenoids, vitamin C, vitamin D, tocopherol (vitamin E), selenium, or trace elements (copper, iron, zinc).
Tea and coffee are two commonly consumed beverages that contain numerous bioactive compounds with anti-carcinogenic potential such as polyphenols and phytochemicals. Evidence from studies measuring the association between tea and coffee consumption and KC in humans is weak and inconsistent, showing either reduced risks of BCC associated with high levels of caffeinated coffee intake or no evidence that overall caffeine consumption was associated with BCC.
These limited findings must be interpreted cautiously, as very few dietary components have been investigated in randomised trials. Most data derive from observational studies, in which dietary measurement is extremely challenging.
Most research interest has focused on human papillomavirus (HPV) and the hypothesis that skin cells infected with beta-HPV types may be transformed by the expression of viral E6 and E7 proteins involved in cell stability. To date, there is relatively little evidence from studies comparing HPV status in people with BCC and in healthy controls without BCC, and available evidence is inconsistent.
Overall, there is no strong evidence that HPV is causally associated with BCC.
Genetic epidemiology[edit source]
Rare, high-risk susceptibility genes[edit source]
The first insights into the genetic causes of BCC were provided by studies of patients with naevoid BCC syndrome (Gorlin's syndrome), a rare autosomal dominant disorder characterised by the development of multiple early-onset BCCs, other cancers, and other phenotypic abnormalities. The primary cause of naevoid BCC syndrome is mutations in the patched 1 gene (PTCH1), a tumour suppressor gene that is a key regulatory component of the hedgehog signalling pathway. Activation of this pathway appears to occur early in BCC development.
Common, low- to moderate-risk susceptibility genes[edit source]
Genome-wide association studies have identified other susceptibility loci, including a variant at 9q21 (containing both the CDKN2A and CDKN2B genes), genes associated with pigmentation traits such as ASIP, TYR, SLC45A2I and MC1R, 1p36, 1q42, variants in the TERT-CLPTM1L locus, and two novel susceptibility loci at TGM3 and RGS22.
TGM3 is thought to influence susceptibility via disturbance of corneocyte differentiation (causing barrier defects), while the function of RGS22 is unclear.
Somatic mutations[edit source]
Sequencing studies show that BCCs have the highest mutation burden of all cancers. Most mutations have a UV radiation signature, especially those of BCCs on chronically exposed anatomic sites. They commonly carry mutations in PTCH1 and TP53 and, to a lesser extent, SMO.
A recent study of 293 BCC tumours identified recurrent mutations in other cancer-related genes including MYCN, PPP6C, STK19, and LATS1, as well ERBB2, PKI3CA and the RAS family.
Sun protection throughout life (including appropriate use of clothing and Therapeutic Good Administration-approved sunscreen labelled SFP30 or higher) should be promoted and encouraged to reduce the risk of basal cell carcinoma.
- Non-melanoma Skin Cancer Working Group. The 2002 national non-melanoma skin cancer survey. Carlton, VIC: National Cancer Control Initiative; 2003 Nov [cited 2018 Oct 8]. Sponsored by Cancer Council. Available from: https://canceraustralia.gov.au/publications-and-resources/cancer-australia-publications/national-cancer-control-initiative-1997-2002-report.
- Buettner PG, Raasch BA. Incidence rates of skin cancer in Townsville, Australia. Int J Cancer 1998 Nov 23;78(5):587-93 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9808527.
- Green A, Battistutta D, Hart V, Leslie D, Weedon D. Skin cancer in a subtropical Australian population: incidence and lack of association with occupation. The Nambour Study Group. Am J Epidemiol 1996 Dec 1;144(11):1034-40 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8942434.
- Marks R, Jolley D, Dorevitch AP, Selwood TS. The incidence of non-melanocytic skin cancers in an Australian population: results of a five-year prospective study. Med J Aust 1989 May 1;150(9):475-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2786135.
- Pandeya N, Olsen CM, Whiteman DC. The incidence and multiplicity rates of keratinocyte cancers in Australia. Med J Aust 2017 Oct 16;207(8):339-343 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29020905.
- Raasch BA, Buettner PG. Multiple nonmelanoma skin cancer in an exposed Australian population. Int J Dermatol 2002 Oct;41(10):652-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12390187.
- Richmond-Sinclair NM, Pandeya N, Ware RS, Neale RE, Williams GM, van der Pols JC, et al. Incidence of basal cell carcinoma multiplicity and detailed anatomic distribution: longitudinal study of an Australian population. J Invest Dermatol 2009 Feb;129(2):323-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18668137.
- Keim U, van der Pols JC, Williams GM, Green AC. Exclusive development of a single type of keratinocyte skin cancer: evidence from an Australian population-based cohort study. J Invest Dermatol 2015 Mar;135(3):728-733 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25233075.
- Staples MP, Elwood M, Burton RC, Williams JL, Marks R, Giles GG. Non-melanoma skin cancer in Australia: the 2002 national survey and trends since 1985. Med J Aust 2006 Jan 2;184(1):6-10 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16398622.
- Australian Institute of Health and Welfare. Skin cancer in Australia. Canberra, ACT: AIHW, Department of Health; 2016 Jul 13 [cited 2018 Oct 8]. Report No.: CAN 96. Available from: https://www.aihw.gov.au/reports/cancer/skin-cancer-in-australia/contents/table-of-contents.
- van Dam RM, Huang Z, Rimm EB, Weinstock MA, Spiegelman D, Colditz GA, et al. Risk factors for basal cell carcinoma of the skin in men: results from the health professionals follow-up study. Am J Epidemiol 1999 Sep 1;150(5):459-68 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10472945.
- Han J, Colditz GA, Hunter DJ. Risk factors for skin cancers: a nested case-control study within the Nurses' Health Study. Int J Epidemiol 2006 Dec;35(6):1514-21 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16943234.
- Khalesi M, Whiteman DC, Tran B, Kimlin MG, Olsen CM, Neale RE. A meta-analysis of pigmentary characteristics, sun sensitivity, freckling and melanocytic nevi and risk of basal cell carcinoma of the skin. Cancer Epidemiol 2013 Oct;37(5):534-43 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23849507.
- Richmond-Sinclair NM, Pandeya N, Williams GM, Neale RE, van der Pols JC, Green AC. Clinical signs of photodamage are associated with basal cell carcinoma multiplicity and site: a 16-year longitudinal study. Int J Cancer 2010 Dec 1;127(11):2622-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20196068.
- Khalesi M, Whiteman DC, Doi SA, Clark J, Kimlin MG, Neale RE. Cutaneous markers of photo-damage and risk of Basal cell carcinoma of the skin: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2013 Sep;22(9):1483-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23833126.
- Jayaraman SS, Rayhan DJ, Hazany S, Kolodney MS. Mutational landscape of basal cell carcinomas by whole-exome sequencing. J Invest Dermatol 2014 Jan;134(1):213-220 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23774526.
- Kricker A, Weber M, Sitas F, Banks E, Rahman B, Goumas C, et al. Early Life UV and Risk of Basal and Squamous Cell Carcinoma in New South Wales, Australia. Photochem Photobiol 2017 Nov;93(6):1483-1491 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28710897.
- Bauer A, Diepgen TL, Schmitt J. Is occupational solar ultraviolet irradiation a relevant risk factor for basal cell carcinoma? A systematic review and meta-analysis of the epidemiological literature. Br J Dermatol 2011 Sep;165(3):612-25 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21605109.
- Gallagher RP, Hill GB, Bajdik CD, Fincham S, Coldman AJ, McLean DI, et al. Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma. Arch Dermatol 1995 Feb;131(2):157-63 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7857111.
- Savoye I, Olsen CM, Whiteman DC, Bijon A, Wald L, Dartois L, et al. Patterns of Ultraviolet Radiation Exposure and Skin Cancer Risk: the E3N-SunExp Study. J Epidemiol 2018 Jan 5;28(1):27-33 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29176271.
- El Ghissassi F, Baan R, Straif K, Grosse Y, Secretan B, Bouvard V, et al. A review of human carcinogens--part D: radiation. Lancet Oncol 2009 Aug;10(8):751-2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19655431.
- Karagas MR, Stannard VA, Mott LA, Slattery MJ, Spencer SK, Weinstock MA. Use of tanning devices and risk of basal cell and squamous cell skin cancers. J Natl Cancer Inst 2002 Feb 6;94(3):224-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11830612.
- Karagas MR, Zens MS, Li Z, Stukel TA, Perry AE, Gilbert-Diamond D, et al. Early-onset basal cell carcinoma and indoor tanning: a population-based study. Pediatrics 2014 Jul;134(1):e4-12 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24958589.
- Stern RS, PUVA Follow-Up Study.. The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study. J Am Acad Dermatol 2012 Apr;66(4):553-62 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22264671.
- Karagas MR, McDonald JA, Greenberg ER, Stukel TA, Weiss JE, Baron JA, et al. Risk of basal cell and squamous cell skin cancers after ionizing radiation therapy. For The Skin Cancer Prevention Study Group. J Natl Cancer Inst 1996 Dec 18;88(24):1848-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8961975.
- Yoshinaga S, Hauptmann M, Sigurdson AJ, Doody MM, Freedman DM, Alexander BH, et al. Nonmelanoma skin cancer in relation to ionizing radiation exposure among U.S. radiologic technologists. Int J Cancer 2005 Jul 10;115(5):828-34 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15704092.
- Sugiyama H, Misumi M, Kishikawa M, Iseki M, Yonehara S, Hayashi T, et al. Skin cancer incidence among atomic bomb survivors from 1958 to 1996. Radiat Res 2014 May;181(5):531-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24754560.
- Maloney ME. Arsenic in Dermatology. Dermatol Surg 1996 Mar;22(3):301-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8599743.
- Boonchai W, Green A, Ng J, Dicker A, Chenevix-Trench G. Basal cell carcinoma in chronic arsenicism occurring in Queensland, Australia, after ingestion of an asthma medication. J Am Acad Dermatol 2000 Oct;43(4):664-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11004623.
- Guo HR, Yu HS, Hu H, Monson RR. Arsenic in drinking water and skin cancers: cell-type specificity (Taiwan, ROC). Cancer Causes Control 2001 Dec;12(10):909-16 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11808710.
- National Health and Medical Research Council, National Resource Management Ministerial Council. Australian Drinking Water Guidelines Paper 6 National Water Quality Management Strategy. Canberra: NHMRC, NRMMC, Commonwealth of Australia; 2011 [cited 2019 Aug 16]. Report No.: Version 3.5 (updated Aug 2018).
- Karagas MR, Stukel TA, Morris JS, Tosteson TD, Weiss JE, Spencer SK, et al. Skin cancer risk in relation to toenail arsenic concentrations in a US population-based case-control study. Am J Epidemiol 2001 Mar 15;153(6):559-65 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11257063.
- Leonardi-Bee J, Ellison T, Bath-Hextall F. Smoking and the risk of nonmelanoma skin cancer: systematic review and meta-analysis. Arch Dermatol 2012 Aug;148(8):939-46 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22711192.
- Song F, Qureshi AA, Gao X, Li T, Han J. Smoking and risk of skin cancer: a prospective analysis and a meta-analysis. Int J Epidemiol 2012 Dec;41(6):1694-705 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23064412.
- Reinau D, Surber C, Jick SS, Meier CR. Epidemiology of basal cell carcinoma in the United Kingdom: incidence, lifestyle factors, and comorbidities. Br J Cancer 2014 Jul 8;111(1):203-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24874476.
- Dusingize JC, Olsen CM, Pandeya NP, Subramaniam P, Thompson BS, Neale RE, et al. Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell Carcinoma. J Invest Dermatol 2017 Aug;137(8):1700-1708 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28414022.
- Pirie K, Beral V, Heath AK, Green J, Reeves GK, Peto R, et al. Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies. Br J Cancer 2018 Jul;119(1):114-120 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29899391.
- Yen H, Dhana A, Okhovat JP, Qureshi A, Keum N, Cho E. Alcohol intake and risk of nonmelanoma skin cancer: a systematic review and dose-response meta-analysis. Br J Dermatol 2017 Sep;177(3):696-707 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28745396.
- Ansems TM, van der Pols JC, Hughes MC, Ibiebele T, Marks GC, Green AC. Alcohol intake and risk of skin cancer: a prospective study. Eur J Clin Nutr 2008 Feb;62(2):162-70 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17392700.
- McNaughton SA, Marks GC, Green AC. Role of dietary factors in the development of basal cell cancer and squamous cell cancer of the skin. Cancer Epidemiol Biomarkers Prev 2005 Jul;14(7):1596-607 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16030089.
- Payette MJ, Whalen J, Grant-Kels JM. Nutrition and nonmelanoma skin cancers. Clin Dermatol 2010 Nov;28(6):650-62 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21034989.
- Song F, Qureshi AA, Han J. Increased caffeine intake is associated with reduced risk of basal cell carcinoma of the skin. Cancer Res 2012 Jul 1;72(13):3282-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22752299.
- Ferrucci LM, Cartmel B, Molinaro AM, Leffell DJ, Bale AE, Mayne ST. Tea, coffee, and caffeine and early-onset basal cell carcinoma in a case-control study. Eur J Cancer Prev 2014 Jul;23(4):296-302 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24841641.
- Miura K, Hughes MC, Green AC, van der Pols JC. Caffeine intake and risk of basal cell and squamous cell carcinomas of the skin in an 11-year prospective study. Eur J Nutr 2014;53(2):511-20 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23824258.
- Miura K, Hughes MC, Arovah NI, van der Pols JC, Green AC. Black Tea Consumption and Risk of Skin Cancer: An 11-Year Prospective Study. Nutr Cancer 2015;67(7):1049-55 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26359536.
- Karagas MR, Nelson HH, Sehr P, Waterboer T, Stukel TA, Andrew A, et al. Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst 2006 Mar 15;98(6):389-95 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16537831.
- Karagas MR, Waterboer T, Li Z, Nelson HH, Michael KM, Bavinck JN, et al. Genus beta human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study. BMJ 2010 Jul 8;341:c2986 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20616098.
- Iannacone MR, Gheit T, Waterboer T, Giuliano AR, Messina JL, Fenske NA, et al. Case-control study of cutaneous human papillomavirus infection in Basal cell carcinoma of the skin. J Invest Dermatol 2013 Jun;133(6):1512-20 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23303448.
- Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med 2004 Nov;6(6):530-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15545751.
- Nikolaou V, Stratigos AJ, Tsao H. Hereditary nonmelanoma skin cancer. Semin Cutan Med Surg 2012 Dec;31(4):204-10 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23174490.
- Daya-Grosjean L, Couvé-Privat S. Sonic hedgehog signaling in basal cell carcinomas. Cancer Lett 2005 Jul 28;225(2):181-92 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15978322.
- Goeteyn M, Geerts ML, Kint A, De Weert J. The Bazex-Dupré-Christol syndrome. Arch Dermatol 1994 Mar;130(3):337-42 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8129412.
- Michaëlsson G, Olsson E, Westermark P. The Rombo syndrome: a familial disorder with vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas and peripheral vasodilation with cyanosis. Acta Derm Venereol 1981;61(6):497-503 Available from: http://www.ncbi.nlm.nih.gov/pubmed/6177160.
- Gudbjartsson DF, Sulem P, Stacey SN, Goldstein AM, Rafnar T, Sigurgeirsson B, et al. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma. Nat Genet 2008 Jul;40(7):886-91 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18488027.
- Stacey SN, Gudbjartsson DF, Sulem P, Bergthorsson JT, Kumar R, Thorleifsson G, et al. Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits. Nat Genet 2008 Nov;40(11):1313-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18849993.
- Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, et al. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 2009 Feb;41(2):221-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19151717.
- Stacey SN, Sulem P, Masson G, Gudjonsson SA, Thorleifsson G, Jakobsdottir M, et al. New common variants affecting susceptibility to basal cell carcinoma. Nat Genet 2009 Aug;41(8):909-14 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19578363.
- Nan H, Xu M, Kraft P, Qureshi AA, Chen C, Guo Q, et al. Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma. Hum Mol Genet 2011 Sep 15;20(18):3718-24 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21700618.
- Stacey SN, Sulem P, Gudbjartsson DF, Jonasdottir A, Thorleifsson G, Gudjonsson SA, et al. Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma. Hum Mol Genet 2014 Jun 1;23(11):3045-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24403052.
- Bonilla X, Parmentier L, King B, Bezrukov F, Kaya G, Zoete V, et al. Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma. Nat Genet 2016 Apr;48(4):398-406 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26950094.
- Scott GA, Laughlin TS, Rothberg PG. Mutations of the TERT promoter are common in basal cell carcinoma and squamous cell carcinoma. Mod Pathol 2014 Apr;27(4):516-23 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24030752.
- Denisova E, Heidenreich B, Nagore E, Rachakonda PS, Hosen I, Akrap I, et al. Frequent DPH3 promoter mutations in skin cancers. Oncotarget 2015 Nov 3;6(34):35922-30 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26416425.