Genetic mutation of breast cancer 1 (
According to the current literature, breast cancer is the most commonly diagnosed form of cancer and is the principal cause of cancer-associated fatality among females. The disease accounts for 14% of all cancer mortalities, particularly in economically-developing countries, and 23% of all cancer cases (
The abnormal methylation of cytosine-phosphate-guanine (CpG) islands in gene promoter regions is the predominant epigenetic mechanism by which gene transcription is effectively silenced; therefore, the transcriptional activity of genes with CpG island promoters is suppressed upon methylation (
The human
The SNPs in the human
The genotype and phenotype correlation was analyzed using the χ2 test. Statistical analysis was performed on SPSS version 21 software (IMB SPSS, Armonk, NY, USA) All statistical tests were two-sided, and P<0.05 was considered to indicate a statistically significance difference.
The online tools NNPP and Promoter2.0 indicated that there were several core promoter regions located in the target sequence. A total of 3 core promoter regions were determined by NNPP, whilst Promoter2.0 identified 2 core promoter regions. The bioinformatics software MethPrimer was used to predict the range of the CpG islands in the
A total of 28 SNPs were identified in the human
As previously reported, the derived alleles at rs12516 and rs8176318 in the
SNPs not in LD (r2<0.8) were selected and LD maps of those SNPs in the
The present study took advantage of the available HapMap-complementary DNA expression database for the correlation analysis between
Since the identification of the
Previous studies have demonstrated that
In conclusion, the current study predicted 3 GpG islands, 45 TFBSs located in the promoter region and 13 SNPs located in the 3′UTR of the
This study was supported by the Foundation for Clinical Medicine Science and Technology Special Project of the Jiangsu Province, China (grant no. BL2014071) to X.G.
CpG island prediction results in the breast cancer 1 gene promoter region. Criteria used to define a CpG island were as follows: Island size, >100; GC percentage, >50.0; and observed/expected ratio, >0.6. CpG, cytosine-phosphate-guanine; PCR, polymerase chain reaction; MSP, methylation-specific PCR.
Linkage disequilibrium plot of the breast cancer 1 gene region using SNP function prediction. The color of each SNP spot reflects its D' value, which changes from red to white as the D' value decreases. SNP, single nucleotide polymorphism; LWK, members of the Luhya tribe in Webuye, Kenya; CHD, Chinese individuals in Metropolitan Denver, Colorado; YRI, members of the Yoruba tribe in Ibadan, Nigeria; MEX, individuals of Mexican ancestry in Los Angeles, California; JPT, Japanese individuals in Tokyo, Japan; GIH, Gujarati Indians in Houston, Texas; CHB, Han Chinese individuals in Beijing, China; CEU, Utah residents with Northern and Western European ancestry from the Center for the Study of Human Polymorphismscollection; LD, linkage disequilibrium; MAF, minor allele frequency; nsSNP, non-synonymous SNP.
Genotype-phenotype association analysis of the mRNA expression level of the
CpG island prediction results.
CpG island | Size, bp | Start | End |
---|---|---|---|
1 | 129 | 412 | 540 |
2 | 244 | 608 | 851 |
3 | 221 | 950 | 1170 |
Criteria used were as follows: Island size, >100 bp; GC percent, >50.0; observed to expected ratio, >0.6. CpG, cytosine-phosphate-guanine.
Selected SNPs of 3′UTR and putative miRNA binding sites.
SNP | Alleles | MAF, % | Putative miRNA binding sites |
---|---|---|---|
rs8176320 | G>A | 0.51 | hsa-miR-101, hsa-miR-15a, hsa-miR-15b, has-miR-16, hsa-miR-194, hsa-miR-195, hsa-miR-424, hsa-miR-450b-5p, hsa-miR-545 |
rs184237074 | C>T | 0.05 | NA |
rs189382442 | T>C | 0.05 | NA |
rs182218567 | A>G | 0.05 | NA |
rs12516 | C>T | 31.18 | hsa-miR-188–5p, hsa-miR-502–5p, hsa-miR-557, hsa-miR-623, hsa-miR-637, hsa-miR-639 |
rs111791349 | C>T | 0.51 | NA |
rs185966495 | G>C | 0.05 | NA |
rs8176319 | C>T | 0.69 | NA |
rs138782023 | T>C | 0.28 | NA |
rs141850147 | G>A | 0.05 | NA |
rs8176318 | G>T | 29.06 | hsa-miR-1182, hsa-miR-149, hsa-miR-345, hsa-miR-544, hsa-miR-639 |
rs56108540 | T>C | 0.23 | hsa-miR-125a-3p, hsa-miR-224, hsa-miR-499–3p, hsa-miR-539, hsa-miR-548c-3p, hsa-miR-767–5p |
rs137892861 | G>A | 0.14 | NA |
SNP, single nucleotide polymorphism; 3′UTR, 3′ untranslated region; miRNA/miR, microRNA; G, guanine; A, adenine; C, cytosine; T, thymine; MAF, minor allele frequency; hsa,
Genotype frequency of the breast cancer 1 gene rs12516 polymorphism in different populations.
Genotype frequency, n (%) | Allele frequency, % | ||||||
---|---|---|---|---|---|---|---|
Populations | n | CC | CT | TT | C | T | HWP |
CEU | 226 | 100 (44.2) | 102 (45.1) | 24 (10.6) | 66.8 | 33.2 | 1.000 |
JPT | 170 | 82 (48.2) | 76 (44.7) | 12 (7.1) | 70.6 | 29.4 | 0.527 |
YRI | 226 | 156 (69.0) | 62 (27.4) | 8 (3.5) | 82.7 | 17.3 | 0.752 |
CHB | 82 | 38 (46.3) | 32 (39.0) | 12 (14.6) | 65.9 | 34.1 | 0.403 |
LWK | 180 | 112 (62.2) | 62 (34.4) | 6 (3.3) | 79.4 | 20.6 | 0.655 |
MEX | 98 | 62 (63.3) | 26 (26.5) | 10 (10.2) | 76.5 | 23.5 | 0.100 |
GIH | 176 | 50 (28.4) | 94 (53.4) | 32 (18.2) | 55.1 | 44.9 | 0.479 |
CHD | 170 | 46 (27.1) | 98 (57.6) | 26 (15.3) | 55.9 | 44.1 | 0.150 |
ASW | 98 | 44 (44.9) | 50 (51.0) | 4 (4.1) | 70.4 | 29.6 | 0.150 |
MKK | 286 | 172 (60.1) | 104 (36.4) | 10 (3.5) | 78.3 | 21.7 | 0.403 |
TSI | 174 | 64 (36.8) | 88 (50.6) | 22 (12.6) | 62.1 | 37.9 | 0.527 |
CEU, Utah residents with Northern and Western European ancestry from the Center for the Study of Human Polymorphisms collection; JPT, Japanese individuals in Tokyo, Japan; YRI, members of the Yoruba tribe in Ibadan, Nigeria; CHB, Han Chinese individuals in Beijing, China; LWK, members of the Luhya tribe in Webuye, Kenya; MEX, individuals of Mexican ancestry in Los Angeles, California; GIH, Gujarati Indians in Houston, Texas; CHD, Chinese individuals in Metropolitan Denver, Colorado; ASW, individuals of African ancestry in Southwest, USA; MKK, members of the Maasai tribe in Kinyawa, Kenya; TSI, Tuscan individuals in Italy; HWP, Hardy-Weinburg probability; C, cytosine; T, thymine.
Genotype frequency of the breast cancer 1 gene rs8176318 polymorphism in different populations.
Genotype frequency, n (%) | Allele frequency, % | ||||||
---|---|---|---|---|---|---|---|
Populations | n | GG | GT | TT | G | T | HWP |
CEU | 226 | 100 (44.2) | 102 (45.1) | 24 (10.6) | 66.8 | 33.2 | 1.000 |
JPT | 172 | 88 (51.2) | 72 (41.9) | 12 (7.0) | 72.1 | 27.9 | 0.752 |
YRI | 226 | 180 (79.6) | 42 (18.6) | 4 (1.8) | 88.9 | 11.1 | 0.584 |
CHB | 82 | 38 (46.3) | 32 (39.0) | 12 (14.6) | 65.9 | 34.1 | 0.403 |
LWK | 180 | 152 (84.4) | 26 (14.4) | 2 (1.1) | 91.7 | 08.3 | 0.655 |
MEX | 98 | 62 (63.3) | 28 (28.6) | 8 (8.2) | 77.6 | 22.4 | 0.251 |
GIH | 176 | 52 (29.5) | 92 (52.3) | 32 (18.2) | 55.7 | 44.3 | 0.584 |
CHD | 170 | 48 (28.2) | 96 (56.5) | 26 (15.3) | 56.5 | 43.5 | 0.200 |
ASW | 98 | 56 (57.1) | 42 (42.9) | 0 (0) | 78.6 | 21.4 | 0.251 |
MKK | 286 | 206 (72.0) | 72 (25.2) | 8 (2.8) | 84.6 | 15.4 | 0.752 |
TSI | 176 | 68 (38.6) | 88 (50.0) | 20 (11.4) | 63.6 | 36.4 | 0.479 |
CEU, Utah residents with Northern and Western European ancestry from the Center for the Study of Human Polymorphisms collection; JPT, Japanese individuals in Tokyo, Japan; YRI, members of the Yoruba tribe in Ibadan, Nigeria; CHB, Han Chinese individuals in Beijing, China; LWK, members of the Luhya tribe in Webuye, Kenya; MEX, individuals of Mexican ancestry in Los Angeles, California; GIH, Gujarati Indians in Houston, Texas; CHD, Chinese individuals in Metropolitan Denver, Colorado; ASW, individuals of African ancestry in Southwest, USA; MKK, members of the Maasai tribe in Kinyawa, Kenya; TSI, Tuscan individuals in Italy; HWP, Hardy-Weinburg probability; C, cytosine; T, thymine; G, guanine.