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Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer.
Cancer Res 2007; 67(19):9591-6CR

Abstract

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by a greatly increased risk of cancer among those diagnosed with the syndrome. The question as to whether FA heterozygotes are at increased risk for cancer is of great importance to those at risk for being a carrier. To address this question, we formed a cohort of grandparents of probands identified through the International Fanconi Anemia Registry. We obtained informed consent, a short questionnaire, and either blood or buccal swab DNA. After diagnosis of the proband was confirmed and complementation studies or DNA sequencing on the proband were completed, mutation analyses of the putative carriers and noncarriers was carried out. Standardized incidence ratios (SIR) were calculated to compare the observed cancer incidence of the grandparents and other relatives with the expected rates of cancer, using the Surveillance, Epidemiology, and End Results registries and the Connecticut Cancer registry. In the 944 study subjects who participated (784 grandparents and 160 other relatives), there was no suggestion of an increase in overall cancer incidence. On the other hand, a significantly higher rate of breast cancer than expected was observed among carrier grandmothers [SIR, 1.7; 95% confidence interval (95% CI), 1.1-2.7]. Among the grandmothers, those who were carriers of FANCC mutations were found to be at highest risk (SIR, 2.4; 95% CI, 1.1-5.2). Overall, there was no increased risk for cancer among FA heterozygotes in this study of Fanconi relatives, although there is some evidence that FANCC mutations are possibly breast cancer susceptibility alleles.

Authors+Show Affiliations

Cancer Research and Treatment Center/Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17909071

Citation

Berwick, Marianne, et al. "Genetic Heterogeneity Among Fanconi Anemia Heterozygotes and Risk of Cancer." Cancer Research, vol. 67, no. 19, 2007, pp. 9591-6.
Berwick M, Satagopan JM, Ben-Porat L, et al. Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer. Cancer Res. 2007;67(19):9591-6.
Berwick, M., Satagopan, J. M., Ben-Porat, L., Carlson, A., Mah, K., Henry, R., ... Auerbach, A. D. (2007). Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer. Cancer Research, 67(19), pp. 9591-6.
Berwick M, et al. Genetic Heterogeneity Among Fanconi Anemia Heterozygotes and Risk of Cancer. Cancer Res. 2007 Oct 1;67(19):9591-6. PubMed PMID: 17909071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer. AU - Berwick,Marianne, AU - Satagopan,Jaya M, AU - Ben-Porat,Leah, AU - Carlson,Ann, AU - Mah,Katherine, AU - Henry,Rashida, AU - Diotti,Raffaella, AU - Milton,Kelly, AU - Pujara,Kanan, AU - Landers,Tom, AU - Dev Batish,Sat, AU - Morales,José, AU - Schindler,Detlev, AU - Hanenberg,Helmut, AU - Hromas,Robert, AU - Levran,Orna, AU - Auerbach,Arleen D, PY - 2007/10/3/pubmed PY - 2007/11/1/medline PY - 2007/10/3/entrez SP - 9591 EP - 6 JF - Cancer research JO - Cancer Res. VL - 67 IS - 19 N2 - Fanconi anemia (FA) is a rare autosomal recessive disease characterized by a greatly increased risk of cancer among those diagnosed with the syndrome. The question as to whether FA heterozygotes are at increased risk for cancer is of great importance to those at risk for being a carrier. To address this question, we formed a cohort of grandparents of probands identified through the International Fanconi Anemia Registry. We obtained informed consent, a short questionnaire, and either blood or buccal swab DNA. After diagnosis of the proband was confirmed and complementation studies or DNA sequencing on the proband were completed, mutation analyses of the putative carriers and noncarriers was carried out. Standardized incidence ratios (SIR) were calculated to compare the observed cancer incidence of the grandparents and other relatives with the expected rates of cancer, using the Surveillance, Epidemiology, and End Results registries and the Connecticut Cancer registry. In the 944 study subjects who participated (784 grandparents and 160 other relatives), there was no suggestion of an increase in overall cancer incidence. On the other hand, a significantly higher rate of breast cancer than expected was observed among carrier grandmothers [SIR, 1.7; 95% confidence interval (95% CI), 1.1-2.7]. Among the grandmothers, those who were carriers of FANCC mutations were found to be at highest risk (SIR, 2.4; 95% CI, 1.1-5.2). Overall, there was no increased risk for cancer among FA heterozygotes in this study of Fanconi relatives, although there is some evidence that FANCC mutations are possibly breast cancer susceptibility alleles. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/17909071/Genetic_heterogeneity_among_Fanconi_anemia_heterozygotes_and_risk_of_cancer_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17909071 DB - PRIME DP - Unbound Medicine ER -