Sunday, 22 April 2012

SNPs: More than just a Snippet of Insight into Breast Cancer

By Saskia Leibowitz

Breast cancer is the most common cancer affecting women worldwide and the most deadly[1]. Exciting developments in science have found links between this disease and genetic mutations. Approximately 20 variants have been identified so far[2], but scientists believe even more are involved[2]. A team of scientists studying this phenomenon noted that most research has involved European descendents whose genetic variants show little association with women from other ethnicities[2]. Therefore, they decided to focus on East Asian women to identify novel genetic susceptibility loci for breast cancer.

The studies were genome-wide association studies (GWAS)[2]. GWAS involve the large-scale analysis of the genomes of subjects with a particular phenotype in order to identify any variations that could be associated with that phenotype – breast cancer, in this case[3][4]. These studies analysed single-nucleotide polymorphisms (SNPs). SNPs are variations in a single base-pair of a DNA sequence[4] which can affect the function of genes. SNPs also act as markers to find genes associated with disease[5]. Watch this video for more on SNPs.

The two studies I looked at each involved genotyping over 600,000 SNPs in East Asian women over several stages and, after statistical analysis, two SNPs that showed strong associations with breast cancer risk were discovered[2][6].

The first study (10,000 women) found a link between breast cancer and SNP rs2046210 in a region of chromosome 6, called 6q25.1[6]. An important gene, ESR1, which encodes estrogen receptor α, is also found in 6q25.1[6]. This gene, crucial to regulating signal transduction (stimulating a cellular response[4]) of the sex hormone estrogen[6], has previously been found to play a role in breast cancer progression[2]. Therefore, rs2046210’s proximity to ESR1 suggests that it could possibly affect ESR1 gene expression and in this way increase susceptibility to breast cancer[6]. The relationship between this SNP and breast cancer is strengthened further by the discovery of a similar association, albeit weaker, in a separate American study of European descendents[6].

Encouraged by their success, the researchers embarked on a much larger study of 40,000 women which successfully identified another SNP (rs9485372) on the same chromosome (6q25.1) as having an association with breast cancer[2]. Notably, rs9485372 is also close to ESR1[2], but it is even closer to the TAB2 gene[2]. TAB2 encodes proteins critical in regulating cell growth and death and has been found to influence breast cancer progression[2]. Therefore, they concluded that the association between rs9485372 and breast cancer risk is possibly mediated through the TAB2 gene[2]. Although the mechanism of these SNPs remains unknown, this study reinforces that intergenic regions, termed “junk DNA”, may possibly affect the functioning of genes.

These studies of East Asian women have found strong evidence that novel susceptibility loci at chromosome 6q25.1, near the TAB2 and ESR1 genes, are associated with breast cancer risk. The results suggest that 6q25.1 constitutes a significant region for breast cancer susceptibility across races[6]. Therefore, this discovery of novel susceptibility loci constitutes a genetic advance in the understanding of breast cancer, highlighting a region of the human genome where further research is necessary.


[1] Parkin, D. M., Pisani, P. and Ferlay, J. (1999), Global cancer statistics. CA: A Cancer Journal for Clinicians, 49: 33–64. doi: 10.3322/canjclin.49.1.33
[2] Long J, Cai Q, Sung H, Shi J, Zhang B, et al. (2012) Genome-Wide Association Study in East Asians Identifies Novel Susceptibility Loci for Breast Cancer. PLoS Genet 8(2): e1002532. doi:10.1371/journal.pgen.1002532
[3] National Institute of Health. (2011). Genome-Wide Association Studies. Available: Last accessed 10th March 2012.
[4]Reece, Meyers, Urry, Cain, Wasserman, Minorsky, Jackson and Cooke (2011). Campbell Biology. 9th ed. Australia: Pearson. 417-418.
[5]Unknown(2012). What are single nucleotide polymorphisms. Available:
[6]Zheng, W., Long, J., Gao, Y., Li, C., et al. (2009). Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nature Genetics. 41 (1), 324 - 328
[7] Sirius Genomics Inc.. (2011). Technology. Available: Last accessed 11th March 2012.
[8]Unknown. (2012). Chromosome 6. Available: Last accessed 10th March 2012.

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