Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population

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.

Diagnostic and prognostic value of serum MACC1 in breast cancer patients

“…We hypothesized that serum MACC1 levels may mirror BC tumor progression and invasion. Consistent with our findings, a separate study associated increased MACC1 in tumor tissues with progressive factors, such as Ki-67 status, TNM stage, tumor size, and lymph node status [25, 26], excluding ER and HER2 status [17]. The association between serum MACC1 and clinical TNM staging in the current study may be explained by the fact that most serum MACC1 originates from tumor tissues.…”

Association of polymorphisms in LOC105377871 and CASC16 with breast cancer in the northwest Chinese Han population

“…There was no blood relationship between the participants and no age limit. The controls were 503 healthy women who had a physical examination in this hospital and were frequency‐matched to the cases by age (±5 years) . All healthy controls were confirmed by mammography examination without a breast cancer.…”

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study

“…This case-control study included 560 patients with BC and 583 cancer-free controls, as we described previously [40, 41]. All participants were recruited without the restrictions of age.…”