Abstract 3275: Genome-wide association study of childhood body fatness as a risk factor of breast cancer

Abstract

Abstract Girls with large body size have a 15-30% reduced risk of developing breast cancer independent of both birth weight and adult body mass index (BMI). The mechanisms underlying this association are poorly understood, especially since large body size at young age is correlated with earlier pubertal timing, a known risk factor for breast cancer. Self-reported childhood body size, a phenotype which is described in the literature as “childhood body fatness”, has an estimated heritability of 70-80% compared to 40-70% for adult BMI and the correlation between childhood body fatness and adult BMI is only modest (r=0.24-0.30). Still, the literature on genetic associations in pediatric body size-related phenotypes is very sparse. We conducted a genome-wide association study (GWAS) of childhood body fatness in 10,560 individuals within the Nurses’ Health Study (NHS) and the Health Professional Follow-up Study (HPFS). All subjects were imputed using the 1000 Genomes Phase I v3 reference panel. Analysis was adjusted for top principal components and study/gender. We observed three regions with p<10-7. Two of the regions (TNNI3K and BCDIN3D) have previously been identified as associated with BMI, the former in adolescents. The third region (1p35.2, p=4.8x10-8) constitutes a potential novel locus associated with childhood body fatness. Five additional regions (4 novel) showed suggestive association with childhood body fatness (p<10-6). We are currently replicating these new regions in additional 9,800 subjects from NHS, HPFS and SASBAC, a Swedish breast cancer case-control study. We will also assess the association between identified loci and breast cancer risk. Such analysis will help elucidate the shared genetic component between childhood body fatness and breast cancer and increase our understanding to why early life fatness decreases breast cancer risk. Citation Format: Sara Lindstrom, Jingmei Li, Hongyan Huang, Constance Chen, David J. Hunter, Per Hall, Peter Kraft, Rulla Tamimi. Genome-wide association study of childhood body fatness as a risk factor of breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3275. doi:10.1158/1538-7445.AM2014-3275