MAD1L1 Arg558His and MAD2L1 Leu84Met interaction with smoking increase the risk of colorectal cancer

• DOI: 10.1038/srep12202
• Publication Date: 2015-07-17T09:09:58Z
• Authors: Rong Zhong; Xiaohua Chen; Xueqin Chen; Beibei Zhu; Jiao Lou; Jiaoyuan Li; Na Shen; Yang Yang; Yajie Gong; Ying Zhu; Jing Yuan; Xiaoping Xia; Xiaoping Miao
• Keywords: BUB1; Mad2; Spindle checkpoint; Binucleated cells; Chromosome instability

The spindle assembly checkpoint (SAC) has been established as an important mechanism of driving aneuploidy, which occurs at a high frequency in the colorectal tumorigenesis. Two components SAC are MAD1L1 and MAD2L1, function together interactive manner to initiate signal. We hypothesize that genetic variants binding domains MAD2L1 may modulate protein structures eventually contribute CRC susceptibility. A case-control study including 710 cases 735 controls was performed examine Arg558His Leu84Met's conferring susceptibility CRC. Cytokinesis-block micronucleus cytome assays were applied assess effect two functional on chromosomal instability (CIN). Significant associations with risk observed for (OR = 1.38,95% CI: 1.09-1.75) Leu84Met dominant model 1.48,95% 1.09-2.01). Moreover, significant multiplicative gene-smoking interactions found (P 0.019) MAD2L184 Leu/Met 0.016) enhance risk. Additionally, frequencies lymphocytic micro-nucleated binucleated cells polymorphism significantly different exposed group 0.013), but not control group. emphasized can interact smoking risk, effects MAD1L1Arg558His CIN need be further clarified follow-up studies.