Variants in 6q25.1 Are Associated with Mammographic Density in Malaysian Chinese Women

Abstract

Background: Mammographic density is an established risk factor for breast cancer and has a strong heritable component. Genome-wide association studies (GWAS) for mammographic density conducted in women of European descent have identified several genetic associations, but none of the studies have been tested in Asians. We sought to investigate whether these genetic loci, and loci associated with breast cancer risk and breast size, are associated with mammographic density in an Asian cohort.Methods: We conducted genotyping by mass spectrometry in 1,189 women (865 Chinese, 187 Indian, and 137 Malay). Quantitative measurements of mammographic density were performed using ImageJ, a fully automated thresholding technique. The associations of SNPs to densities were analyzed using linear regression models.Results: We successfully evaluated the associations of 36 SNPs with mammographic densities. After adjusting for age,

Understanding mammographic breast density profile in China: A Sino‐Australian comparative study of breast density using real‐world data from cancer screening programs

“…9,31 Even though there are many studies of mammographic density of Chinese women, majority of these works explored Chinese women living in Western countries [32][33][34][35][36][37][38][39][40][41][42][43] or in Southeast Asia. 29,[44][45][46][47][48][49][50][51][52] To the best of our knowledge, only five papers were China-based work, 13,22,53,54 including one from Hong Kong Special Administrative Region. 55 Almost all of these five studies used women from local/city-level screening program or hospital-based data, three studies showed that age was negatively correlated with mammographic density, 13,22,53 and two of them reported a negative relationship for BMI.…”

“…Even though there are many studies of mammographic density of Chinese women, majority of these works explored Chinese women living in Western countries 32–43 or in Southeast Asia 29,44–52 . To the best of our knowledge, only five papers were China‐based work, 13,22,53,54 including one from Hong Kong Special Administrative Region 55 .…”

A Comprehensive Screening Strategy of Breast Cancer Based on Different Penetrance Susceptibility Genes in Healthy Han Chinese Females

“…Elevated estrogen levels have been shown to be associated with an increased risk of breast cancer in previous studies [50]. It is hypothesized that rs2046210 together with ESR1 may play an essential role in estrogen-dependent mammary epithelial proliferation, which is associated with increased mammographic density and subsequent risk to BC [51][52][53]. Other loci, such as rs10474352 [54], rs6788895 [55], rs7107217 et al [56], were also identified in previous studies in HCW and have the potential to be a predictive variable to asses the risk of BC.…”

Identification of novel common breast cancer risk variants at the 6q25 locus among Latinas

“…This differential effect is unexpected since estrogen signaling via ER is believed to increase the risk of ER-positive breast cancer and not have an effect on ER-negative breast cancer [54, 55]. However, ESR1 could also exert an effect via the stroma and many of the variants at this locus are known to affect mammographic density [27–30] which is associated with both ER-positive and ER-negative breast cancer [56]. Furthermore, other genes at this locus including ARMT1, CCDC170 , and RMND1 may also be candidates for an effect on breast cancer risk [27, 57–59].…”

“…Several GWAS studies have identified SNPs at 6q25 that are associated with breast cancer risk [13, 18, 20, 23–27] and mammographic density [23, 27–30]. The initial report identified a SNP in the intergenic region between ESR1 and CDCC170 in an East Asian population [24].…”