In the first large study of its kind, a team of researchers led by epidemiologists from the Roswell Park Cancer Institute (NY, USA) have provided new information that may help to explain why many African–American women have an increased risk of being diagnosed with aggressive forms of breast cancer.
The study, which was published recently in the International Journal of Cancer, reinforces existing evidence that increases in dietary folate may be an effective method for risk reduction in African–American women. The research, focused on differences in folate-regulated one-carbon metabolism – a complicated network of interdependent processes responsible for key cell processes such as DNA methylation, replication and repair, and nucleotide synthesis.
In this case–control study of 1299 African–American and 1275 European–American women who participated in the Women’s Circle of Health Study (a multisite study to evaluate risk factors for early and aggressive forms of breast cancer), the team performed a comprehensive analysis of SNPs in 11 genes that are involved in one-carbon metabolism and risk of breast cancer.
The results demonstrated distinct patterns in these SNPs between the two groups of women. Associations were also identified between a number of these SNPs (in particular in genes such as MTR, MTRR, SHMT1, TYMS and SLC19A1) and overall risk of breast cancer, and also with breast cancer risk by estrogen-receptor status. Although the single-SNP associations were not statistically significant after adjusting for key factors, their polygenetic risk-score analyses identified significant associations between the variations and breast cancer risk.
In addition to these findings, the results of the study, which has investigated genes that have not previously been well studied in breast cancer, have led to new discoveries regarding the metabolism of key enzymes and has highlighted that SNP associations could potentially be altered by the level of dietary intake of folate.
“These findings are provocative because they provide new evidence that, by disrupting key processes and ultimately contributing to gene instability, certain genetic variants and interactions in these key metabolic pathways may contribute to risk of breast cancer in both African–American and European–American women,” commented Zhihong Gong from the Roswell Park Cancer Institute.
The authors note that further large-scale studies and functional evaluations are required to both confirm their findings and to investigate the molecular mechanisms that are responsible for these dynamics. The study researchers plan to investigate further the associations between dietary folate intake, blood folate levels and genotypes of these key SNPs to provide more information on differences in association by race and to investigate potential associations with breast cancer outcomes.