Background: Germline variations may contribute to lung cancer susceptibility besides environmental factors. The influence of germline mutations on lung cancer susceptibility and their correlation with somatic mutations has not been systematically investigated.Methods: In this study, germline mutations from 1,026 non-small cell lung cancer (NSCLC) patients were analyzed with a 58-gene next-generation sequencing (NGS) panel containing known hereditary cancerrelated genes, and were categorized based on American College of Medical Genetics and Genomics (ACMG) guidelines in pathogenicity, and the corresponding somatic mutations were analyzed using a 605-gene NGS panel containing known cancer-related genes.Results: Plausible genetic susceptibility was found in 4.7% of lung cancer patients, in which 14 patients with pathogenic mutations (P group) and 34 patients with likely-pathogenic mutations (LP group) were identified. The ratio of the first degree relatives with lung cancer history of the P groups was significantly higher than the Non-P group (P=0.009). The ratio of lung cancer patients with history of other cancers was higher in P (P=0.0007) or LP (P=0.017) group than the Non-P group. Pathogenic mutations fell most commonly in BRCA2, followed by CHEK2 and ATM. Likely-pathogenic mutations fell most commonly in NTRK1 and EXT2, followed by BRIP1 and PALB2. These genes are involved in DNA repair, cell cycle regulation and tumor suppression. By comparing the germline mutation frequency from this study with that from the whole population or East Asian population (gnomAD database), we found that the overall odds ratio (OR) for P or LP group was 17.93 and 15.86, respectively, when compared with the whole population, and was 2.88 and 3.80, respectively, when compared with the East Asian population, suggesting the germline mutations of the P and LP groups were risk factors for lung cancer. Somatic mutation analysis revealed no significant difference in tumor mutation burden (TMB) among the groups, although a trend of lower TMB in the pathogenic group was found. The SNV/INDEL mutation frequency of TP53 in the P group was significantly lower than the other two groups, and the copy number variation (CNV) mutation frequency of PIK3CA and MET was significantly higher than the Non-P group. Pathway enrichment analysis found no significant difference in aberrant pathways among the three groups.Conclusions: A proportion of 4.7% of patients carrying germline variants may be potentially linked to increased susceptibility to lung cancer. Patients with pathogenic germline mutations exhibited stronger family history and higher lung cancer risk.

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Recurrent spontaneous abortion (RSA) is a health problem that affects nearly 1% of fertile couples. However, the underlying etiology and mechanism(s) remain elusive. The aim of this study was to investigate estrogen receptor (ESR) 1 gene polymorphisms for risk association of unexplained recurrent spontaneous abortion (URSA) in the Chinese Han population. The entire coding region of the ESR1 gene was sequenced from 129 URSA patients and 183 healthy controls. There was a significant difference between the G allele and GG genotype distributions, of the ESR1 gene (XbaI) polymorphism, between the URSA and the control groups ( 2 ¼ 14.93, df ¼ 1, p50.001, OR ¼ 2.01 95% CI: 1.41-2.88 by allele; 2 ¼ 12.24, df ¼ 2, p ¼ 0.002 by genotype). The PvuII polymorphism, C allele frequency was higher in RSA than in controls (41.9% vs. 34.7%, respectively). Women carrying C-G haplotype were associated with an increased risk of URSA in this population (permutation test p value ¼ 0.016, OR ¼ 1.76 95% CI: 1.19-2.59). Estrogen receptor 1 gene PvuII and XbaI polymorphisms were associated with URSA in a Chinese Han population. However, independent replication of these associations are necessary to assure veracity.

BackgroundDevelopmental dysplasia of the hip (DDH) is a congenital or acquired deformation or misalignment of the hip joint which affects mainly females. We hypothesized that HOXD9 gene could be regulated in acetabular size or shape and related in DDH developing.MethodsTwo hundred and nine Chinese Han female DDH patients and 173 ethnic, age matched healthy female controls were genotyped for HOXD9 two tag SNPs using sequenom method.ResultsOne of the two tag SNPs, rs711822, was not shown significantly differences in genotypic or allelic distribution between case and control group. Comparing the genotypic distribution of rs711819, there was significant differences between DDH patients group and control group (χ2 = 7.54, df =2, P =0.023), and the association to DDH developing reached significance (P =0.045, OR =1.79, 95 % CI: 1.01-3.17 by dominant mode).ConclusionIn conclusion, the association between one tag SNP of HOXD9 gene and the development of DDH reach significant in our study population, this result indicate the positive correlation between HOXD9 gene and DDH developing. Further study in larger sample size and different population as well as functional studies will help to understand the pathogenesis of DDH.