title: DNA variants in the ATM gene are not associated with sporadic rectal cancer in a Norwegian population-based study.
abstract: OBJECTIVE
  A large number of DNA single-nucleotide polymorphisms (SNPs) have been discovered following the Human Genome Project. Several projects have been launched to find associations between SNPs and various disease cohorts. This study examined the possible association between the reported SNPs and sporadic rectal cancer. It has been proposed that SNPs in the ataxi-telangiectasia mutated (ATM) gene modulate the penetrance of some cancers. The investigated target sequence harbors three polymorphisms (IVS38-8 T/C in intron 38, 5557 G/A and 5558 A/T in exon 39), resulting in eight possible microhaplotypes at the DNA level. Furthermore, the two exonic SNPs are sited next to each other, allowing four possible amino acids in the same codon.
  
  
  METHODS
  We report on a new method analyzing SNPs and microhaplotypes based on theoretical thermodynamics and migration of variant fragments by cycling temperature capillary electrophoresis. Fluorophore-labeled PCR products were analyzed without any post-PCR steps on a standard 96 capillary-sequencing instrument under denaturing conditions.
  
  
  RESULTS
  More than 7000 alleles were microhaplotyped based on peak migration patterns of individual samples and sequencing results. The ATM polymorphisms and microhaplotypes examined did not significantly differ between sporadic rectal cancer and normal population.
  
  
  CONCLUSIONS
  No associations were found between the IVS38-8 T/C, 5557 G/A and 5558 A/T polymorphisms and microhaplotypes in the ATM gene with respect to sporadic rectal cancer.
authors.affiliation: Department of Surgical Oncology, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, 0310, Oslo, Norway.
authors.forename: Annette Torgunrud
authors.initials: AT
authors.lastname: Kristensen
authors.forename: Jens
authors.initials: J
authors.lastname: Bjørheim
authors.forename: Johan
authors.initials: J
authors.lastname: Wiig
authors.forename: Karl E
authors.initials: KE
authors.lastname: Giercksky
authors.forename: Per O
authors.initials: PO
authors.lastname: Ekstrøm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001260:Ataxia Telangiectasia; D064007:Ataxia Telangiectasia Mutated Proteins; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D004586:Electrophoresis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016350:Leucine Zippers; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D019869:Phosphatidylinositol 3-Kinases; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human