When it comes to cervical cancer, the first culprit you think of must be human papillomavirus (HPV). This is a common virus that spreads through sexual contact. However, most HPV infections resolve spontaneously, and less than 4% of individuals will develop persistent infections, which may lead to precancerous lesions or cancer. This indicates that there is also a complex relationship between the host genetic characteristics and the virus.
In order to identify the genetic risk factors for cervical cancer, researchers from many institutions such as Tongji Medical College of Huazhong University of Science and Technology conducted a genome-wide association study (GWAS) among the Han population and found two new susceptibility sites for cervical cancer. The research results were published in the journal Nature Genetics in August. Leading this research is Professor Martin of Huazhong University of Science and Technology.
In developing countries, cervical cancer is one of the most important malignant tumors that causes women to die. A large amount of epidemiological and clinical evidence indicates that the persistent infection of high-risk HPV is the main risk factor and necessary for the development of cervical cancer; HPV infection is detected in 99.7% of cervical cancer cases. However, simple HPV infection is not enough to cause tumor development, and most infections can resolve on their own. Various signs indicate that cervical cancer is also associated with genetic factors and external environmental factors.
Therefore, the researchers conducted a large-scale GWAS study among the Han population. First, at the discovery stage, they used Affymetrix's Axiom Genome-Wide CHB1 chip to genotype 1,364 cases and 3,028 female controls. Axiom Genome-Wide CHB1 is a chip designed specifically for the Han population. Its content is selected from the Axiom Genome Database, which maximizes the coverage of common alleles (MAF> 5%). At this stage, the researchers found a total of 41 clearly associated SNPs.
After that, they conducted a second-stage follow-up study on 22 of these 41 SNP sites (19 of which were ignored in linkage disequilibrium). This stage includes two independent sample groups: the first group includes 1,824 cases and 3,808 controls; the second group includes 2,343 cases and 3,388 controls. For the first group, 13 of the 22 SNPs were statistically significant. Subsequently, they conducted genotyping of the 13 SNPs in the second group.
Combining the results of these three stages, the researchers found two new SNP sites (rs1311117307 and rs8067378), and the chromosomal regions where they are located or adjacent (EXOC1 [4q12] and GSDMB [17q12]) are susceptible regions of cervical cancer . At the same time, the researchers also confirmed a previously identified site (rs4282438), which is located between HLA-DPB1 and HLA-DPB2 on 6p21.32 (HLA-DPB1 / 2).
The researchers believe that the EXOC and GSDMB regions, as well as the identification of susceptible sites in the HLA-DP allele, suggest that T cell-mediated immune responses or tumor cell proliferation may play an important role. These genetic factors may affect the mechanism of continuous infection and integration of HPV, which is related to the risk of cervical cancer. This discovery provides new insights into the genetic cause of cervical cancer and is of great significance for the prevention and treatment of cancer.
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