Genetic heterogeneity among fanconi anemia heterozygotes and risk of cancer

Marianne Berwick, Jaya M. Satagopan, Leah Ben-Porat, Ann Carlson, Katherine Mah, Rashida Henry, Raffaella Diotti, Kelly Milton, Kanan Pujara, Tom Landers, Sat Dev Batish, José Morales, Detlev Schindler, Helmut Hanenberg, Robert Hromas, Orna Levran, Arleen D. Auerbach

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)9591-9596
Number of pages6
JournalCancer Research
Volume67
Issue number19
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Fingerprint

Fanconi Anemia
Genetic Heterogeneity
Heterozygote
Neoplasms
Incidence
Registries
Mutation
Confidence Intervals
Breast Neoplasms
Cheek
Informed Consent
DNA Sequence Analysis
Epidemiology
Alleles
Grandparents
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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), 9591-9596. https://doi.org/10.1158/0008-5472.CAN-07-1501

Genetic heterogeneity among fanconi anemia heterozygotes and risk of cancer. / Berwick, Marianne; Satagopan, Jaya M.; Ben-Porat, Leah; Carlson, Ann; Mah, Katherine; Henry, Rashida; Diotti, Raffaella; Milton, Kelly; Pujara, Kanan; Landers, Tom; Batish, Sat Dev; Morales, José; Schindler, Detlev; Hanenberg, Helmut; Hromas, Robert; Levran, Orna; Auerbach, Arleen D.

In: Cancer Research, Vol. 67, No. 19, 01.10.2007, p. 9591-9596.

Research output: Contribution to journalArticle

Berwick, M, Satagopan, JM, Ben-Porat, L, Carlson, A, Mah, K, Henry, R, Diotti, R, Milton, K, Pujara, K, Landers, T, Batish, SD, Morales, J, Schindler, D, Hanenberg, H, Hromas, R, Levran, O & Auerbach, AD 2007, 'Genetic heterogeneity among fanconi anemia heterozygotes and risk of cancer', Cancer Research, vol. 67, no. 19, pp. 9591-9596. https://doi.org/10.1158/0008-5472.CAN-07-1501
Berwick M, Satagopan JM, Ben-Porat L, Carlson A, Mah K, Henry R et al. Genetic heterogeneity among fanconi anemia heterozygotes and risk of cancer. Cancer Research. 2007 Oct 1;67(19):9591-9596. https://doi.org/10.1158/0008-5472.CAN-07-1501
Berwick, Marianne ; Satagopan, Jaya M. ; Ben-Porat, Leah ; Carlson, Ann ; Mah, Katherine ; Henry, Rashida ; Diotti, Raffaella ; Milton, Kelly ; Pujara, Kanan ; Landers, Tom ; Batish, Sat Dev ; Morales, José ; Schindler, Detlev ; Hanenberg, Helmut ; Hromas, Robert ; Levran, Orna ; Auerbach, Arleen D. / Genetic heterogeneity among fanconi anemia heterozygotes and risk of cancer. In: Cancer Research. 2007 ; Vol. 67, No. 19. pp. 9591-9596.
@article{93c49186ca61415fb652d8488022a7b9,
title = "Genetic heterogeneity among fanconi anemia heterozygotes and risk of cancer",
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.",
author = "Marianne Berwick and Satagopan, {Jaya M.} and Leah Ben-Porat and Ann Carlson and Katherine Mah and Rashida Henry and Raffaella Diotti and Kelly Milton and Kanan Pujara and Tom Landers and Batish, {Sat Dev} and Jos{\'e} Morales and Detlev Schindler and Helmut Hanenberg and Robert Hromas and Orna Levran and Auerbach, {Arleen D.}",
year = "2007",
month = "10",
day = "1",
doi = "10.1158/0008-5472.CAN-07-1501",
language = "English (US)",
volume = "67",
pages = "9591--9596",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "19",

}

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 - Batish, Sat Dev

AU - Morales, José

AU - Schindler, Detlev

AU - Hanenberg, Helmut

AU - Hromas, Robert

AU - Levran, Orna

AU - Auerbach, Arleen D.

PY - 2007/10/1

Y1 - 2007/10/1

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=35148853561&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35148853561&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-07-1501

DO - 10.1158/0008-5472.CAN-07-1501

M3 - Article

VL - 67

SP - 9591

EP - 9596

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 19

ER -