posters International Association for Breast Cancer Research 2014

Replication study of genome-wide significant mammographic density SNPs in Asian women (#53)

Shivaani Mariapun 1 , Peter C.E. Kang 1 , Jingmei Li 2 , Sara Lindstrom 3 , Cheng Har Yip 4 , Soo Hwang Teo 1
  1. University of Malaya/Cancer Research Initiatives Foundation, Subang Jaya, S'GOR, Malaysia
  2. Human Genetics, Genome Institute of Singapore, Singapore
  3. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
  4. Surgery, Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia

Mammographic density is an established risk factor for breast cancer which has a strong genetic component. Identifying genetic factors that influence this trait may be important in understanding breast cancer pathogenesis. Genome-wide association studies for density conducted in women of European descent have identified several genetic associations. We sought to investigate whether these associations are also present in our cohort of Asian women. We also sought to determine whether SNPs associated with breast cancer risk in Asians and breast size in Europeans modify density in our study population.

Ten loci that were previously found to have associations to mammographic density in the Western population and two loci that were previously identified among East Asian women were selected for genotyping by mass spectrometry in our cohort of 1203 Chinese, Malay and Indian women. Twenty-three SNPs associated with breast cancer risk in Asians and six SNPs associated with breast size in European women were also genotyped. Quantitative measurements of density were performed using an automated thresholding technique. The association of these SNPs to density was analysed using linear regression models.

After adjusting for age, BMI, parity, menopausal status and ethnicity, we found that two SNPs that were associated with density in the Western population (Chr4q13.3 and Chr6q25.1) and two SNPs that were associated with breast size in the Western population (Chr4q13.3 and Chr6q25.1) were significantly associated with percent density (P<0.05) in our cohort after Bonferroni correction for multiple comparisons. We however did not find an association between density and any of the breast cancer susceptibility SNPs that were analysed.

Our study shows SNPs found to mediate density and breast size in women with European ancestry also mediate that in our Asian cohort in the same direction. The small sample size may have resulted in reduced power to identify other potentially significant associations.

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