Abstract 1655: Genome-wide association study for age at onset in breast cancer: results from the Seoul Breast Cancer Study

Abstract

Abstract Introduction: While the incidence of breast cancer is relatively low in Korean women, the proportion of breast cancer that develops in younger age is much higher than in western countries. Family-based linkage study has focused on the identification of a region which is associated with the age at onset in familial breast cancer. However, genetic factors for onset age of breast cancer are still largely unknown. While genome-wide association studies (GWAS) have identified over 20 susceptibility loci for breast cancer, no previous study has examined the relationship between the common genetic variations and the age at onset in breast cancer. Methods: To identify genetic factors underlying onset age of breast cancer, we investigated the association between genetic variants and age at diagnosis in 2,155 breast cancer cases. Over 1.9 million SNPs either directly genotyped using Affymetrix 6.0 or imputed with HapMap 2.0 as a reference panel were evaluated after quality control. Tests of association were conducted with Plink v1.01 using the additive genetic model and Mach2qtl with allelic dosages in a linear regression model in which onset age was included as a dependent variable (continuous). The differences of mean age across genotype-groups were also compared using one-way analysis of variance. Results: The mean age at onset in breast cancer was 48.1 ± 9.31. The SNPs with p-value less than 1×10-5 obtained from linear regression were clustered into two regions: two SNPs (rs6684400 and rs6659875) are at 1q25.3 in intergenic region between ZNF648 and GLUL gene; the other two (rs669576 and rs667007) are at 11q25 in intronic region of NTM gene. Per-allele effect size was 1.4 ± 0.30 (p = 4.84E-06) for rs6684400 C allele and 3.1 ± 0.68 for rs669576 T allele (p = 7.11E-06). The mean age at onset for the rs6684400 G/G, C/G and C/C groups were found to be 47.2 ± 9.00, 48.1 ± 9.32 and 49.7 ± 9.59, respectively (p = 0.0001). As for the rs669576, the mean age at onset for G/G, G/T and T/T groups were 47.8 ± 9.15, 50.9 ± 10.38 and 54.3 ± 7.80, respectively (p < 0.0001) Conclusions: Our study suggests that the common genetic variants may be closely linked to age at onset in breast cancer. Further validation with a larger sample size is required to validate our result. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1655. doi:1538-7445.AM2012-1655