Cancer incidence in relatives of British Fanconi Anaemia patients.
BACKGROUND
Fanconi anemia (FA) is an autosomal recessive DNA repair disorder with affected individuals having a high risk of developing acute myeloid leukaemia and certain solid tumours. Thirteen complementation groups have been identified and the genes for all of these are known (FANCA, B, C, D1/BRCA2, D2, E, F, G, I, J/BRIP1, L, M and N/PALB2). Previous studies of cancer incidence in relatives of Fanconi anemia cases have produced conflicting results. A study of British FA families was therefore carried out to investigate this question, since increases in cancer risk in FA heterozygotes would have implications for counselling FA family members, and possibly also for the implementation of preventative screening measures in FA heterozygotes.


METHODS
Thirty-six families took part and data was collected on 575 individuals (276 males, 299 females), representing 18,136 person years. In this cohort, 25 males and 30 females were reported with cancer under the age of 85 years, and 36 cancers (65%) could be confirmed from death certificates, cancer registries or clinical records.


RESULTS
A total of 55 cancers were reported in the FA families compared to an estimated incidence of 56.95 in a comparable general population cohort, and the relative risk of cancer was 0.97 (95% C.I. = 0.71-1.23, p = 0.62) for FA family members. Analysis of relative risk for individual cancer types in each carrier probability group did not reveal any significant differences with the possible exception of prostate cancer (RR = 3.089 (95% C.I. = 1.09 - 8.78; Chi2 = 4.767, p = 0.029).


CONCLUSIONS
This study has not shown a significant difference in overall cancer risk in FA families.
Tischkowitz
Marc
M
Cancer Genetics Program, Departments of Human Genetics and Oncology, Sir M.B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada. marc.tischkowitz@mcgill.ca
Easton
Douglas F
DF
Ball
Jan
J
Hodgson
Shirley V
SV
Mathew
Christopher G
CG
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005192:Family Health; D005199:Fanconi Anemia / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
Nat Genet. 2007 Feb;39(2):142-3
17262024
Nat Genet. 2006 Nov;38(11):1239-41
17033622
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6788-93
17420451
Blood. 2006 Jun 1;107(11):4223-33
16493006
Cancer Res. 2003 Dec 15;63(24):8596-9
14695169
Cancer Res. 2007 Oct 1;67(19):9591-6
17909071
Mutat Res. 1992 Dec 1;284(1):25-36
1279391
Br J Haematol. 2004 Jul;126(2):176-91
15238138
Nat Genet. 2007 Feb;39(2):165-7
17200668
Nature. 1971 Apr 9;230(5293):370-3
4927726
Cancer Genet Cytogenet. 1983 May;9(1):61-5
6839307
Cell. 2007 Apr 20;129(2):289-301
17412408
Nat Genet. 2006 Aug;38(8):873-5
16832357
Nature. 2007 Mar 15;446(7133):316-9
17287723
J Natl Cancer Inst. 2005 Jun 1;97(11):813-22
15928302
J Natl Cancer Inst. 1999 Aug 4;91(15):1310-6
10433620
J Natl Cancer Inst. 1980 Nov;65(5):863-7
6933255
Oncogene. 2006 Sep 25;25(43):5875-84
16998502