Evaluating Genome-Wide Association Study-Identified Breast Cancer Risk Variants in African-American Women

Abstract

Genome-wide association studies (GWAS), conducted mostly in European or Asian descendants, have identified approximately 67 genetic susceptibility loci for breast cancer. Given the large differences in genetic architecture between the African-ancestry genome and genomes of Asians and Europeans, it is important to investigate these loci in African-ancestry populations. We evaluated index SNPs in all 67 breast cancer susceptibility loci identified to date in our study including up to 3,300 African-American women (1,231 cases and 2,069 controls), recruited in the Southern Community Cohort Study (SCCS) and the Nashville Breast Health Study (NBHS). Seven SNPs were statistically significant (P≤0.05) with the risk of overall breast cancer in the same direction as previously reported: rs10069690 (5p15/TERT), rs999737 (14q24/RAD51L1), rs13387042 (2q35/TNP1), rs1219648 (10q26/FGFR2), rs8170 (19p13/BABAM1), rs17817449 (16q12/FTO), and rs13329835 (16q23/DYL2). A marginally significant association (P<0.10) was found for three additional SNPs: rs1045485 (2q33/CASP8), rs4849887 (2q14/INHBB), and rs4808801 (19p13/ELL). Three additional SNPs, including rs1011970 (9p21/CDKN2A/2B), rs941764 (14q32/CCDC88C), and rs17529111 (6q14/FAM46A), showed a significant association in analyses conducted by breast cancer subtype. The risk of breast cancer was elevated with an increasing number of risk variants, as measured by quintile of the genetic risk score, from 1.00 (reference), to 1.75 (1.30–2.37), 1.56 (1.15–2.11), 2.02 (1.50–2.74) and 2.63 (1.96–3.52), respectively, (P = 7.8×10–10). Results from this study highlight the need for large genetic studies in AAs to identify risk variants impacting this population.

Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

“…Breast cancer is one of the most common disorders in women worldwide (Long et al, 2013). Along with multifactorial, genetic background plays a well-established role in cancer etiology (Ayoub et al, 2011).…”

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

“…In fact, a meta‐analysis revealed that various FTO SNPs were associated with different cancers such as endometrial cancer, pancreatic cancer and breast cancer dependent on or independent of BMI adjustment 54. In addition, aberrant expression or mutation of FTO has been shown to have an intimate link with prostate cancer,55 endometrial cancer56 and breast cancer 57, 58, 59, 60. However, the potential role of FTO as a demethylase remains a nascent yield to be explored.…”

N6‐methyladenosine modification in mRNA: machinery, function and implications for health and diseases

“…For instance, WTAP is a key antigen in leukaemia [126], and mutation of FTO is associated with a high occurrence of colorectal cancer and carcinoma cell cultures, endometrial carcinomas, and stomach cancer [131]. High incidence rates of prostate cancer risk [132], breast cancer [133,134] and pancreatic cancer [135] have also been linked to allelic variants of FTO. Furthermore, phosphorylation of METTL3 has been correlated with cellular DNA damage [136] and tumorigenesis, suggesting a possible role of this modification in the onset and progression of cancer.…”