BACKGROUND: The autosomal recessive chromosomal instability disorder Nijmegen breakage syndrome (NBS) is associated with increased risk of lymphoid malignancies and other cancers. Cells from NBS patients contain many double-stranded DNA breaks. More than 90% of NBS patients are homozygous for a founder mutation, 657del5, in the NBN gene. We investigated the 657del5 carrier status of cancer patients among blood relatives (i.e., first-, through fourth-degree relatives) of NBS patients in the Czech Republic and Slovakia to test the hypothesis that NBN heterozygotes have an increased cancer risk. METHODS: Medical information was compiled from 344 blood relatives of NBS patients in 24 different NBS families from January 1, 1998, through December 31, 2003. The 657del5 carrier status of subjects was unknown at the time of their recruitment but was later determined from blood samples collected at the time of the interview. Medical records and death certificates were used to confirm a diagnosis of cancer. For the relatives with cancer who are not obligate heterozygotes (such as parents and two grandparents in consanguineous families), the observed and expected number of mutation carriers were compared by use of the index-test method, which estimated the risk of cancer associated with carrying the mutation. All P values were two-sided. RESULTS: Thirteen of the 344 blood relatives had confirmed cases of any type of cancer; 11 of these 13 cancer patients carried the NBN 657del5 mutation, compared with 6.0 expected (P = .005). Among the 56 grandparents with complete data from 14 NBS families, 10 of the 28 carriers of 657del5, but only one of the 28 noncarriers, developed cancer (odds ratio = 10.7, 95% CI = 1.4 to 81.5; P<.004). CONCLUSIONS: The NBN 657del5 mutation appears to be associated with an elevated risk of cancer in heterozygotes.
BACKGROUND: The autosomal recessive chromosomal instability disorder Nijmegen breakage syndrome (NBS) is associated with increased risk of lymphoid malignancies and other cancers. Cells from NBSpatients contain many double-stranded DNA breaks. More than 90% of NBSpatients are homozygous for a founder mutation, 657del5, in the NBN gene. We investigated the 657del5 carrier status of cancerpatients among blood relatives (i.e., first-, through fourth-degree relatives) of NBSpatients in the Czech Republic and Slovakia to test the hypothesis that NBN heterozygotes have an increased cancer risk. METHODS: Medical information was compiled from 344 blood relatives of NBSpatients in 24 different NBS families from January 1, 1998, through December 31, 2003. The 657del5 carrier status of subjects was unknown at the time of their recruitment but was later determined from blood samples collected at the time of the interview. Medical records and death certificates were used to confirm a diagnosis of cancer. For the relatives with cancer who are not obligate heterozygotes (such as parents and two grandparents in consanguineous families), the observed and expected number of mutation carriers were compared by use of the index-test method, which estimated the risk of cancer associated with carrying the mutation. All P values were two-sided. RESULTS: Thirteen of the 344 blood relatives had confirmed cases of any type of cancer; 11 of these 13 cancerpatients carried the NBN657del5 mutation, compared with 6.0 expected (P = .005). Among the 56 grandparents with complete data from 14 NBS families, 10 of the 28 carriers of 657del5, but only one of the 28 noncarriers, developed cancer (odds ratio = 10.7, 95% CI = 1.4 to 81.5; P<.004). CONCLUSIONS: The NBN657del5 mutation appears to be associated with an elevated risk of cancer in heterozygotes.
Authors: Adam J de Smith; Geneviève Lavoie; Kyle M Walsh; Sumeet Aujla; Erica Evans; Helen M Hansen; Ivan Smirnov; Alice Y Kang; Martin Zenker; John J Ceremsak; Elliot Stieglitz; Ivo S Muskens; William Roberts; Roberta McKean-Cowdin; Catherine Metayer; Philippe P Roux; Joseph L Wiemels Journal: Genes Chromosomes Cancer Date: 2019-05-27 Impact factor: 5.006
Authors: Ewelina Maria Kałużna; Jolanta Rembowska; Iwona Ziółkowska-Suchanek; Bogna Świątek-Kościelna; Piotr Gabryel; Wojciech Dyszkiewicz; Jerzy Stanisław Nowak Journal: Oncol Lett Date: 2015-09-17 Impact factor: 2.967