title: Common low-penetrance risk variants associated with breast cancer in Polish women.
abstract: BACKGROUND
  Breast cancer is the most common type of cancer and the second leading cause of cancer-death among women in Poland. The known high-risk mutations account for 25% of familial aggregation cases and 5% of total breast cancer predisposition. Genome-wide association studies have identified a number of common low-penetrance genetic variants, but their contribution to disease risk differs between populations.
  
  
  METHODS
  To verify selected associations with breast cancer susceptibility among Polish women, the replication study was performed, included 1424 women with breast cancer and 1788 healthy persons. Sixteen single-nucleotide polymorphisms (SNPs) were analyzed using TaqMan SNP Genotyping Assays. Allele frequency differences were tested using chi2-test implemented in PLINK v1.07 and Cochran-Armitage trend test was performed using R software.
  
  
  RESULTS
  Significant differences (Bonferroni corrected p-valuecor ≤ 0.0197) in the frequency of alleles distribution between all cancer and control subjects were observed for four (rs2736098, rs13281615, rs1219648, rs2981582) out of 16 SNPs. The same result was obtained for group of patients without high-risk BRCA1/2 mutations. The rs1219648 (p-valuecor ≤ 6.73E-03) and rs2981582 (p-valuecor ≤ 6.48E-03) SNPs showed significant association with both familial and sporadic cancers. Additionally, rs2736098 (p-valuecor ≤ 0.0234) was associated with only sporadic cancers; also in group without carriers of high-risk mutation. All these associations revealed their significance also in Cochran-Armitage trend test. Opposite to other SNPs, rs2736098 was associated with a decreased risk of breast cancer.
  
  
  CONCLUSIONS
  The association of four known susceptibility SNPs, representing three individual loci, with breast cancer risk in Polish women was confirmed. One of them (rs2736098) seems to be specific for the Polish population. Due to the population differences in allele frequencies, identification of general genetic risk factors requires sets of association studies conducted on different populations.
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Ledwoń
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw, Poland. hennige@coi.waw.pl.
authors.forename: Ewa E
authors.initials: EE
authors.lastname: Hennig
authors.forename: Natalia
authors.initials: N
authors.lastname: Maryan
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Goryca
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
authors.forename: Anna
authors.initials: A
authors.lastname: Niwińska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ostrowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009154:Mutation; D019683:Penetrance; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics; D055815:Young Adult