A combined analysis of genome-wide association studies in breast cancer

Abstract

In an attempt to identify common disease susceptibility alleles for breast cancer, we performed a combined analysis of three genome-wide association studies (GWAS), involving 2,702 women of European ancestry with invasive breast cancer and 5,726 controls. Tests for association were performed for 285,984 SNPs. Evidence for association with SNPs in genes in specific pathways was assessed using a permutation-based approach. We confirmed associations with loci reported by previous GWAS on 1p11.2, 2q35, 3p, 5p12, 8q24, 10q23.13, 14q24.1 and 16q. Six SNPs with the strongest signals of association with breast cancer, and which have not been reported previously, were typed in two further studies; however, none of the associations could be confirmed. Suggestive evidence for an excess of associations was found for genes involved in the regulation of actin cytoskeleton, glycan degradation, alpha-linolenic acid metabolism, circadian rhythm, hematopoietic cell lineage and drug metabolism. Androgen and oestrogen metabolism, a pathway previously found to be associated with the development of postmenopausal breast cancer, was marginally significant (P = 0.051 [unadjusted]). These results suggest that further analysis of SNPs in these pathways may identify associations that would be difficult to detect through agnostic single SNP analyses. More effort focused in these aspects of oncology can potentially open up promising avenues for the understanding of breast cancer and its prevention.

Prostate Stem Cell Antigen Single Nucleotide Polymorphisms Influence Risk of Estrogen Receptor Negative Breast Cancer in Korean Females

“…Recent many genome wide association studies confirmed that prostate, endometrium, breast, gastric and bladder cancer susceptibility linked with the 8q24 locus (Garcia-Closas and Chanock, 2008;Li et al, 2010;Thomas et al, 2009). While 8q24 itself is non-coding and non-genic region, it encompasses established cancer related regions (128,101,433~128,828,043 bp from telomere); the prostate cancer region 3, breast/prostate cancer region, prostate cancer region 1, bladder cancer region, and MYC (Chu et al, 2010).…”

Breast cancer risk, nightwork, and circadian clock gene polymorphisms

“…Using genome-wide data, and grouping the genetic variants by biological pathways, Li et al (2011) reported suggestive evidence of an association of breast cancer with genes involved in the circadian rhythm. Thus, conducting analyses at the geneor pathway level may be helpful to examine the overall effect of circadian gene polymorphisms on breast cancer.…”

Identification of genetic markers with synergistic survival effect in cancer

“…To assess whether Geninter is able to detect true and false positive SNP-pairs we generated a simulator based on 1,000 breast cancer samples chosen from a cohort of breast cancer patients and controls genotyped on the HumanHap550 SNP microarrays [16]. We estimated the genotype frequencies using these 1,000 samples and randomly chosen 150 SNPs.…”

“…Genotype data were obtained on Finnish breast cancer patients genotyped as described previously [16]. Briefly, the patient set comprised two series of unselected breast cancer patients and additional familial cases diagnosed at the Helsinki University Central Hospital (HUCH).The first patient set was collected in 1997-1998 and 2000 and covers 79% of all consecutive, newly diagnosed cases during the collection periods [17,18].…”