FaCD Online Syndrome Fact Sheet

Last updated: 03 Jul 2009

Name: Basal or Squamous Cell Skin Cancer, Familial Clustering of

Synonym: Familial Non-Melanoma Skin Cancer

Mode of Inheritance: multifact?

Tumor features

skin cancer, basal cell
skin cancer, squamous cell

Tumor features (possible)

melanoma, cutaneous
melanoma, uveal (choroidal, ciliary body, iris)/ocular


Basal cell skin cancer
The influence of a family history of skin cancer on basal cell skin cancer (BCC) risk is controversial. Two studies could not demonstrate a familial risk factor[1;2]. However, Wallberg et al[3] found a family history of skin cancer (not further specified) among siblings and/or parents to be the strongest risk factor (relative risk RR = 10.9) of 12 factors tested. The authors could not explain this risk by correcting for hereditary pigmentary characteristics, as for example skin type, eye and hair color, which are known to be associated with melanoma as well as non-melanoma skin cancer risk[4]. Hogan et al.[5] also found that a family history of skin cancer was associated with an increased risk to develop BCC (RR 1.22). In their series of 538 BCC patients and matched controls, they also observed a significantly lower age at diagnosis in those BCC patients with a family history of skin cancer compared with those who did not. In a case-control study of similar size, Naldi et al.[6] confirmed the significant association of BCC and a family history of skin cancer (odds ratio 6.7). In a population-based cohort study of twins, the co-twin of a twin affected with BCC cancer was shown to have an increased BCC risk (RR 7-8), however zygosity did not influence this risk[7;8]. In general, BCC in children in the absence of known genetic conditions is rare, but has been diagnosed at the age of 4 years and older[9].
Several gene polymorphisms have been associated with an increased risk to develop (multiple) BCC[e.g. see 10-12], we do not list them separately in this file.

Squamous cell skin cancer
For squamous cell skin cancer (SCC), a positive family history of skin cancer (in general) also increases SCC risk, as has been calculated by Hogan et al.[13], Gamble et al.[14] and Hemminki and Dong[15].The latter study from the Swedish Family-Cancer Database reported standardized incidence ratios (SIRs) of 2.4 for invasive SCC and 2.8 for invasive SCC in the offspring of parents with SCC. SIR for SCC in offspring of parents with multiple SCC was 70% higher than in offspring of parents with single SCC. The authors also reported a familial association between SCC and skin and ocular melanoma. Risk of invasive squamous cell skin cancer for individuals with an affected sibling or parent was increased between two- and three-fold compared with that in the general population[18].


[1] Maia M, Proenca NG, de Moraes JC. Risk factors for basal cell carcinoma: a case-control study. Rev Saude Publica 1995; 29(1):27-37.
[2] Gellin GA, Kope AW, Garfinkel L. Basal cell epithelioma: A controlled study of associated factors. Arch Dermatol 1965; 91:38-45.
[3] Wallberg P, Kaaman T, Lindberg M. Multiple basal cell carcinoma - A clinical evaluation of risk factors. Acta Derm Venereol (Stockh) 78[2], 127-129. 1998.
[4] Armstrong BK, Kricker A. Epidemiology of sun exposure and skin cancer. Cancer Surv 26, 133-153. 1996.
[5] Hogan DJ, To T, Gran L, Wong D, Lane PR. Risk factors for basal cell carcinoma. Int J Dermatol 1989; 28(9):591-594.
[6] Naldi L, DiLandro A, D'Avanzo B, Parazzini F. Host-related and environmental risk factors for cutaneous basal cell carcinoma: evidence from an Italian case-control study. J Am Acad Dermatol 2000; 42(3):446-452.
[7] Milan T, Kaprio J, Verkasalo PK, Jansen CT, Teppo L, Koskenvuo M. Hereditary factors in basal cell carcinoma of the skin: a population-based cohort study in twins. Br J Cancer 78[11], 1516-1520. 1998.
[8] Bataille V, Snieder H, MacGregor A, Spector T. Hereditary factors in basal cell carcinoma of the skin: a population-based cohort study in twins [letter]. Br J Cancer 2000; 82(1):247-249.
[9] LeSueur BW, Silvis NG, Hansen RC. Basal cell carcinoma in children: report of 3 cases. Arch Dermatol 2000; 136(3):370-372.
[10] Lear J, Heagerty A, Smith A, Bowers B, Jones P, Gilford J, Alldersea J, Fryer A, Strange R. Polymorphism in detoxifying enzymes and susceptibility to skin cancer. Photochem.Photobiol. 63[4], 424-428. 1996.
[11] Lear JT, Heagerty AHM, Smith A, Bowers B, Payne CR, Smith CAD, Jones PW, Gilford J, Yengi L, Alldersea J, Fryer AA, Strange RC. Multiple cutaneous basal cell carcinomas: Glutathione S- transferase (GSTM1, GSTT1) and cytochrome P450 (CYP2D6, CYP1A1) polymorphisms influence tumour numbers and accrual. Carcinogenesis 17[9], 1891-1896. 1996.
[12] Heagerty A, Smith A, English J, Lear J, Perkins W, Bowers B, Jones P, Gilford J, Alldersea J, Fryer A, Strange RC. Susceptibility to multiple cutaneous basal cell carcinomas: Significant interactions between glutathione S-transferase GSTM1 genotypes, skin type and male gender. Br J Cancer 1996; 73:44-48.
[13] Hogan DJ, Lane PR, Gran L, Wong D. Risk factors for squamous cell carcinoma of the skin in Saskatchewan, Canada. J Dermatol Sci 1990; 1(2):97-101.
[14] Gamble JF, Lerman SE, Holder WR, Nicolich MJ, Yarborough CM. Physician-based case-control study of non-melanoma skin cancer in Baytown, Texas. Occup Med Oxf 1996; 46(3):186-196.
[15] Hemminki K, Dong C. Familial relationships in squamous cell carcinoma of the skin. Epidemiology 2000; 11:309-314.
[16] Hemminki K, Zhang H, Czene K. Familial invasive and in situ squamous cell carcinoma of the skin. British journal of cancer 2003; 88(9):1375-80.
[17] Hemminki K, Li X, Czene K. Familial risk of cancer: data for clinical counseling and cancer genetics. International journal of cancer. Journal international du cancer 2004; 108(1):109-14.
[18] Hussain SK, Sundquist J, Hemminki K. The Effect of Having an Affected Parent or Sibling on Invasive and In Situ Skin Cancer Risk in Sweden. J Invest Dermatol. 2009 Feb 26. [Epub ahead of print]