FaCD Online Syndrome Fact Sheet

Last updated: 28 Mar 2008

Name: Cervical Cancer, Familial Clustering of

Mode of Inheritance: multifact?

Tumor features

cervical cancer
ovarian cancer (i.e. epithelial origin)

Tumor features (possible)

anal cancer
hepatocellular cancer (hepatoma)
laryngeal cancer
lung/bronchial cancer
lymphoma, malignant (Non-Hodgkin and/or Hodgkin)
oral cancer
oropharyngeal cancer
penile cancer
rectal cancer
skin cancer
skin cancer, squamous cell
urinary bladder cancer
vulvar squamous cell cancer


Familial clustering of cervical cancer has been reported[1-4,15]. An estimated 15 % of patients with this tumor have at least one affected first degree relative[1]. It has been calculated that having a first degree relative with cervical cancer is associated with a relative risk (RR) of 3 to develop squamous cell cancer of the cervix, a RR of 10 of developing adenosquamous cancer at this site and no increased risk to develop cervical adenocarcinoma [1]. No other studies have confirmed these detailed findings so far.

Data from the Swedish Family-Cancer Database showed a cervical cancer RR of 2.0 for daughters of affected mothers[5]. Subsequently, more detailed analysis the following figures were reported[6]: daughters of mothers with in situ cancer had a RR of 1.7 of developing in situ and RR of again 1.7 of invasive cancer. Daughters of mothers with invasive cervical cancer had a RR of 1.6 of developing in situ cancer and a RR of 2.0 to develop invasive cancer. The following other cancer types in mothers increased the risk for in situ and/or invasive cervical cancer in their daughters: lung, liver, urinary bladder and oral cancer. The following cancer types in daughters increased the risk for in situ and/or invasive cervical cancer in their mothers: lymphoma, ovarian, oral, skin and anorectal cancer. In a more recent study[12] clustering of other human papillomavirus-associated cancers was studied in this Swedish population. Offspring cancer risk was significantly increased when either a sibling or parent was affected at the same site for penile squamous cell carcinoma (SCC) (SIR = 7.54), cervical adenocarcinoma (AC) (SIR = 2.31), vulvar SCC (SIR = 2.27), skin SCC (SIR = 2.14), rectal AC (SIR = 1.86), in situ cervical SCC (SIR = 1.80), invasive cervical SCC (SIR = 1.77) and upper aerodigestive tract SCC (SIR = 1.57). Cervical SCC-in-situ risk in offspring was strongly influenced by oropharyngeal SCC (SIR = 3.17) and tonsillar SCC (SIR = 1.84) in siblings.

An analysis of large Mormon families did not show increased risks of cervical cancer in women with an affected sister[7]. However, an excess of cervical cancer was observed in first-degree relatives of patients with early-onset bladder cancer (RR 2.32). A family history of cancer in general was no risk factor for cervical cancer in a Yugoslavian and a Japanese cohort[8;9]. A study of Finnish patients with borderline ovarian tumors and their relatives demonstrated a RR of 7.8 for cervical cancer in the mothers of index cases[10]. In a Swedish twin study, the increase in risk of cervical cancer tended to be greater if monozygotic rather than dizygotic twins were affected[11] and the same was true for siblings versus half-siblings[17] and first-degree versus second-degree relatives[18].

A range of gene polymorphisms and gene locations, not reviewed and listed here, has been found in association with cervical cancer and possibly contribute to a less effective immunoresponse to Humane Papilloma Virus (HPV) infections, a major risk factor for this tumor.[15,16]


[1] Furgyik S, Grubb R, Kullander S, Sandahl B, Wingerup L, Eydal A. Familial occurrence of cervical cancer, stages 0-IV. Acta Obstet Gynecol Scand 1986; 65(3):223-227.
[2] Brinton LA, Tashima KT, Lehman HF, Levine RS, Mallin K, Savitz DA, Stolley PD, Fraumeni jr JF. Epidemiology of cervical cancer by cell type. Cancer Res 1987; 47:1706-1711.
[3] Bruinse HW, te Velde ER, de Gast BC. Human leukocyte antigen patterns in a family with cervical cancer. Gynecol Oncol 1981; 12:249-252.
[4] Bender S. Carcinoma in-situ of cervix in sisters. Br Med J 1976; i:502.
[5] Hemminki K, Vaittinen P, Kyyronen P. Age-specific familial risks in common cancers of the offspring. Int J Cancer 78[2], 172-175. 1998.
[6] Hemminki K, Dong C, Vaittinen P. Familial risks in cervical cancer: is there a hereditary component? Int J Cancer 1999; 82(6):775-781.
[7] Cannon L, Bishop DT, Skolnick M, Hunt S, Lyon JL, Smart CR. Genetic epidemiology of prostate cancer in the Utah Mormon genealogy. Cancer Surv 1982; 1(1):47-69.
[8] Kessler II, Kulcar Z, Zimolo A, Grgurevic M, Strnad M, Goodwin BJ. Cervical cancer in Yugoslavia. II. Epidemiologic factors of possible etiologic significance. J Natl Cancer Inst 1974; 53(1):51-60.
[9] Sasagawa T, Dong Y, Saijoh K, Satake S, Tateno M, Inoue M. Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical cancer in Japan. Jpn J Cancer Res 1997; 88(4):376-384.
[10] Auranen A, Grenman S, Makinen J, Pukkala E, Sankila R, Salmi T. Borderline ovarian tumors in Finland: Epidemiology and familial occurrence. Am J Epidemiol 144[6], 548-553. 1996.
[11] Ahlbom A, Lichtenstein P, Malmstrom H, Feychting M, Hemminki K, Pedersen NL. Cancer in twins: Genetic and nongenetic familial risk factors. J Natl Cancer Inst 89[4], 287-293. 1997.
[12] Hussain SK, Sundquist J, Hemminki K. Familial clustering of cancer at human papillomavirus-associated sites according to the Swedish Family-Cancer Database. International journal of cancer. Journal international du cancer 2008; 122(8):1873-8.
[13] Magnusson PK, Gyllensten UB. Cervical cancer risk: is there a genetic component? Mol Med Today 2000; 6(4):145-148.
[14] Zoodsma M, Sijmons RH, de Vries EGE, van der Zee AGJ. Familial Cervical Cancer: Case Reports, Review and Clinical Implications. Hereditary Cancer in Clinical Practice 2004;2:99-105.
[15] Engelmark MT, Ivansson EL, Magnusson JJ, Gustavsson IM, Beskow AH, Magnusson PK, Gyllensten UB. Identification of susceptibility loci for cervical carcinoma by genome scan of affected sib-pairs. Human molecular genetics 2006; 15(22):3351-60.
[16] Engelmark M, Beskow A, Magnusson J, Erlich H, Gyllensten U. Affected sib-pair analysis of the contribution of HLA class I and class II loci to development of cervical cancer. Human molecular genetics 2004; 13(17):1951-8.
[17] Hemminki K, Chen B. Familial risks for cervical tumors in full and half siblings: etiologic apportioning. Cancer epidemiology, biomarkers & prevention 2006; 15(7):1413-4.
[18] Couto E, Hemminki K. Heritable and environmental components in cervical tumors. International journal of cancer. Journal international du cancer 2006; 119(11):2699-701.