title: Pathology of breast cancer in women with constitutional CHEK2 mutations.
abstract: The power of association studies between polymorphic genetic variants and breast cancer may be enhanced if the cancer subjects are subclassified by histologic subgroup. In this study we classified 482 unselected breast cancers from Szczecin, Poland by histology (ductal, lobular, medullary, other). All women were genotyped for three founder mutations in the CHEK2 gene (1100delC, IVS2 + 1G > A and I157T). There was no significant overall association between CHEK2 and breast cancer (OR = 1.3; p = 0.30), but among those with lobular carcinoma the association with the I157T missense mutation was very strong (OR = 6.6; p > 0.0001). This is the first report to demonstrate that different mutations of the same gene may be associated with specific histologic subtypes of cancer.
authors.affiliation: Pomeranian Medical University, Szczecin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Wenancjusz
authors.initials: W
authors.lastname: Domagała
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Marek
authors.initials: M
authors.lastname: Szwiec
authors.forename: Stanisław
authors.initials: S
authors.lastname: Woyke
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D044584:Carcinoma, Ductal / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000235:genetics*; D018276:Carcinoma, Medullary / Q000235:genetics*; D064447:Checkpoint Kinase 2; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense; D011044:Poland; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012306:Risk
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases