PMID- 17909071
OWN - NLM
STAT- MEDLINE
DCOM- 20071031
LR  - 20211020
IS  - 0008-5472 (Print)
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 19
DP  - 2007 Oct 1
TI  - Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer.
PG  - 9591-6
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.
FAU - Berwick, Marianne
AU  - Berwick M
AD  - Cancer Research and Treatment Center/Internal Medicine, University of New Mexico, 
      Albuquerque, New Mexico, USA.
FAU - Satagopan, Jaya M
AU  - Satagopan JM
FAU - Ben-Porat, Leah
AU  - Ben-Porat L
FAU - Carlson, Ann
AU  - Carlson A
FAU - Mah, Katherine
AU  - Mah K
FAU - Henry, Rashida
AU  - Henry R
FAU - Diotti, Raffaella
AU  - Diotti R
FAU - Milton, Kelly
AU  - Milton K
FAU - Pujara, Kanan
AU  - Pujara K
FAU - Landers, Tom
AU  - Landers T
FAU - Dev Batish, Sat
AU  - Dev Batish S
FAU - Morales, Jose
AU  - Morales J
FAU - Schindler, Detlev
AU  - Schindler D
FAU - Hanenberg, Helmut
AU  - Hanenberg H
FAU - Hromas, Robert
AU  - Hromas R
FAU - Levran, Orna
AU  - Levran O
FAU - Auerbach, Arleen D
AU  - Auerbach AD
LA  - eng
GR  - M01 RR000102/RR/NCRR NIH HHS/United States
GR  - R01 CA082678-04/CA/NCI NIH HHS/United States
GR  - UL1RR024143/RR/NCRR NIH HHS/United States
GR  - M01RR000102/RR/NCRR NIH HHS/United States
GR  - R37 HL032987/HL/NHLBI NIH HHS/United States
GR  - UL1 RR024143/RR/NCRR NIH HHS/United States
GR  - R01 CA098438/CA/NCI NIH HHS/United States
GR  - R01CA82678/CA/NCI NIH HHS/United States
GR  - R01CA098438/CA/NCI NIH HHS/United States
GR  - R01 CA082678/CA/NCI NIH HHS/United States
GR  - R37HL32987/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
SB  - IM
MH  - Breast Neoplasms/genetics
MH  - Fanconi Anemia/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Neoplasms/*genetics
PMC - PMC3622247
MID - NIHMS250819
EDAT- 2007/10/03 09:00
MHDA- 2007/11/01 09:00
PMCR- 2013/04/10
CRDT- 2007/10/03 09:00
PHST- 2007/10/03 09:00 [pubmed]
PHST- 2007/11/01 09:00 [medline]
PHST- 2007/10/03 09:00 [entrez]
PHST- 2013/04/10 00:00 [pmc-release]
AID - 67/19/9591 [pii]
AID - 10.1158/0008-5472.CAN-07-1501 [doi]
PST - ppublish
SO  - Cancer Res. 2007 Oct 1;67(19):9591-6. doi: 10.1158/0008-5472.CAN-07-1501.