| Background and Objective:Breast cancer (BC) is a serious hazard to life and health of female cancer, the incidence and mortality were ranks first in women all over the world. Epidemiological surveys showed that the incidence of breast cancer was a significant in family aggregation, and exhibited individual differences in susceptibility and ethnic in different population, and the result suggested that genetic factors may play an important role in the pathogenesis of breast cancer. Therefore, make more genetic association analysis of specific populations, can further clarify the cause of breast cancer, and provide scientific basis for prevention, diagnosis and treatment strategies for breast cancer.Methods:We performed a candidate genes case-control study in Shaanxi region. This case-control study of 561 patients with BC and 583 control individuals were conducted from January 2011 to November 2014. We analyzed 48 BC-associated single nucleotide polymorphisms (SNPs) identified in previous GWASs, association studies and meta-analysis studies. Chi-square test was performed to Plink Software and logistic regression model analysis of the SNP genotyping were used SNP Stats (http://bioinfo.iconcologia.net/SNPstats web) online analysis software. Linkage disequilibrium (LD) analysis was done using genotype data from all the subjects. D’and the haplotypes of the candidate SNPs were analyzed using SHEsis Software.Results:Chi-square statistics showed:13 loci rs616488, rs6678914, rs1432679, rs17530068, rs3757318, rs3734805, rs2046210, rs10759243, rs10822013, rs6001930, rs981782, genotype rs4849887 and rs704010 were significant differences in the frequency distribution between breast cancer cases and controls.SNPStats logistic regression analysis showed nine loci were related to breast cancer risk after adjusted by age and body mass index (BMI). Rs616488, located on PEX14, the genotype "C/T" of rs616488 was associated with decreased 27% BC risk with OR= 0.73, P= 0.015. The minor alleles of other eight SNPs were associated with increased risk of breast cancer in different genetic model. It included rs981782 located in HCN1,rs17530068 located between RPL17P25 and FAM46A, rs3757318 and rs3734805 were located in CCDC170, rs2046210 located between CCDC170 and ESR1, rs10759243 located between KLF4 and RPL36AP6, rs704010 located in ZMIZ1, those seven SNPs not only significant associated between BC in logistic regression genotypes analysis, but also significant in Chi-square test between cases and controls. Additionally, we found rs4973768 located in SLC4A7, also significant associated with increased BC rirk in logistic regression genotypes analysis, but not significant in previous Chi-square test.Use SHEsis software analysis the LD (linkage disequilibrium) found two blocks in chromosome 5 and chromosome 6. Rs16886165 (physical location 56,023,083) located between RPL26P19 and MAP3K1, rs889312 (physical location 56,031,884) were strong linkage on the chromosome 5. Rs3734805 (physical location 151939 350) located in CCDC170, rs2046210 (physical location 151948366) located in between CCDC170 and ESRl were strong linkage on the chromosome 6. Further hapbtype analysis showed that only one block consisted two SNPs hapbtype rs3734805 and rs2046210, the hapbtype "CT" on the chromosome 6 the frequency was 0.3184, was significant increase risk of breast cancer with odds ratio (OR)= 1.31,95% confidence interval (CI)= 1.08-1.58, P= 0.006.Estrogen receptor-positive and negative, progesterone receptor positive and negative, TNM stage 1-2 and 3-4 stages subgroup analysis found that in addition to the significant SNPs before in all groups, we also found four SNPs were significant in subgroups: rs10510102 and rs3817198 were found associated with risk of breast cancer subgroups in ER+ and ER- groups, respectively. Rs16857609 was found associated with breast cancer risk only in PR+groups. Rs3817198 and rs1292011 were found to be associated with risk of breast cancer in the TNM 1-2 and TNM 3-4 stage groups.Conclusion:Our results show that 9 SNPs (rs616488, rs981782, rsl7530068, rs3757318, rs3734805, rs2046210, rs10759243, s2046210, rs4973768) were associated with breast cancer in Chinese Han population of Shaanxi region, but the results and the mechanism needs further verification and studies. Stratified analysis added four loci rs10510102, rs3817198, rs13387042, rsl6857609 and rs1292011 may also be associated with different subgroups of breast cancer. These positive SNPs we found were consistent withprevious studies, but there are still many SNPs had been reported in other populations does not significant in our study. |
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