title: Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population: A STROBE-Compliant Observational Study.
abstract: Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk.We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test.There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61-0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55-0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff-Bloom-Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively).Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women.
authors.affiliation: From the Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University (Z-JD, X-HL, H-FK, X-JW, S-QZ, X-BM, MW, Y-JF, KL, PX, H-TG); and National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University (T-BJ, TF), Xi'an, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Dai
authors.forename: Xing-Han
authors.initials: XH
authors.lastname: Liu
authors.forename: Hua-Feng
authors.initials: HF
authors.lastname: Kang
authors.forename: Xi-Jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Tian-Bo
authors.initials: TB
authors.lastname: Jin
authors.forename: Shu-Qun
authors.initials: SQ
authors.lastname: Zhang
authors.forename: Tian
authors.initials: T
authors.lastname: Feng
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Ma
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Yan-Jing
authors.initials: YJ
authors.lastname: Feng
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Guan
mesh_terms: D044466:Asian People; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C544162:MACC1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors