Identification of a breast cancer susceptibility locus at 4q31.22 using a genome-wide association study paradigm

PLoS One. 2013 May 22;8(5):e62550. doi: 10.1371/journal.pone.0062550. Print 2013.

Abstract

More than 40 single nucleotide polymorphisms (SNPs) for breast cancer susceptibility were identified by genome-wide association studies (GWASs). However, additional SNPs likely contribute to breast cancer susceptibility and overall genetic risk, prompting this investigation for additional variants. Six putative breast cancer susceptibility SNPs identified in a two-stage GWAS that we reported earlier were replicated in a follow-up stage 3 study using an independent set of breast cancer cases and controls from Canada, with an overall cumulative sample size of 7,219 subjects across all three stages. The study design also encompassed the 11 variants from GWASs previously reported by various consortia between the years 2007-2009 to (i) enable comparisons of effect sizes, and (ii) identify putative prognostic variants across studies. All SNP associations reported with breast cancer were also adjusted for body mass index (BMI). We report a strong association with 4q31.22-rs1429142 (combined per allele odds ratio and 95% confidence interval = 1.28 [1.17-1.41] and P combined = 1.5×10(-7)), when adjusted for BMI. Ten of the 11 breast cancer susceptibility loci reported by consortia also showed associations in our predominantly Caucasian study population, and the associations were independent of BMI; four FGFR2 SNPs and TNRC9-rs3803662 were among the most notable associations. Since the original report by Garcia-Closas et al. 2008, this is the second study to confirm the association of 8q24.21-rs13281615 with breast cancer outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Breast Neoplasms / genetics*
  • Female
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Risk

Grants and funding

This work was supported by Alberta Cancer Research Institute (ACRI), CBCF (Canadian Breast Cancer Foundation) operating grants and Alberta Cancer Board (ACB) operating grants to SD. Funding for the CBCF Tumor Bank was provided by the CBCF-Prairies/North West Territories Region, Alberta Cancer Foundation, Alberta Cancer Prevention and Legacy Fund, managed by the Alberta Innovates-Health Solutions. The Tomorrow Project was funded by the Alberta Cancer Foundation and the Alberta Cancer Prevention Legacy (managed by Alberta Innovates –Health Solutions) and the Canadian Partnership Against Cancer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.