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The biosynthesis of unsaturated fatty acids is involved in the initiation and progression of colon adenocarcinoma (COAD). In this study, we aimed to investigate the multi-omics characteristics of unsaturated fatty acid biosynthesis-related genes and explore their prognostic value in colon cancer by analyzing the data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. An unsaturated fatty acid biosynthesis pathway related-genes enrichment score (BUFAS) was constructed utilizing the single sample gene set enrichment analysis (ssGSEA). We discovered that a high BUFAS was associated with longer overall survival (OS) in both the training and the validation sets. Multivariable analysis including the clinical characteristics further verified the independent prognostic value of the BUFAS in both the TCGA-COAD and the GSE39582 datasets. In addition, GSEA analysis revealed that BUFAS was positively associated with several signaling pathways, including MTORC1, peroxisome, and pathways related to fatty acid metabolism, while was negatively associated with other signaling pathways, such as hedgehog, NOTCH, and Wnt/beta-catenin pathway. Furthermore, in the COAD cell lines of the Genomics of Drug Sensitivity in Cancer (GDSC) database, we found that BUFAS was positively correlated with the drug sensitivities of cisplatin, gemcitabine, camptothecin, lapatinib, and afatinib, while was negatively correlated with that of ponatinib. Moreover, in the COAD single-cell transcriptomic dataset (GSE146771), the BUFAS varied among different cell types and was enriched in mast cells and fibroblasts. Taken together, the BUFAS we constructed could be used as an independent prognostic signature in predicting the OS and drug resistance of colon cancer. Unsaturated fatty acid biosynthesis pathway might serve as potential therapeutic targets for cancer treatment., Competing Interests: None., (AJCR Copyright © 2022.)

Common burden tests have different statistical performance in genetic association studies of rare variants. Here, we compare the statistical performance of burden tests, such as CMC, WST, SUM and extension methods, using the computer-simulated datasets of rare variants with different parameters of sample sizes, linkage disequilibrium (LD), and different numbers of mixed non-associated variants. The simulation results showed that the type I error for all methods is near 0.05. When the rare variants had the same direction of effect, the higher LD and the less non-associated variants, the higher the power of these method, except the data adaptive SUM test. When the direction was different, the power was significantly reduced for all methods. The methods that consider the direction yielded larger statistical power than those methods without considering the effect direction, except the strong LD condition. And the larger the sample size, the larger the power. The statistical performance of burden tests is affected by a variety of factors, including the sample size, effect direction of variants, non-associated variants, and LD. Therefore, when choosing the method and setting the collection unit and weight, the prior biological information of genetic variation should be integrated to improve study efficiency.

Aim: To examine the effect of the potential interaction between KIF1B variants (rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma (HCC) in a high-risk region in China., Methods: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms (SNPs) of KIF1B (rs17401966 and rs3748578) were chosen for the current study. All subjects were genotyped using a TaqMan real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions., Results: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus (HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio (OR) = 12.02; 95% confidence interval (95%CI): 6.02-24.00]. No significant association was found between the KIF1B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption (P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC (OR = 2.36; 95%CI: 1.49-3.74)., Conclusion: The gene-environment interaction between the KIF1B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.

Aim: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer., Methods: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies., Results: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found., Conclusion: Chronic HBV and HCV infection increases pancreatic cancer risk. Our findings underscore the need for more studies to confirm this potential relationship.

Objective: To evaluate the interaction between environmental factors, HBV/HCV infections and DNA repair gene XPC exon 8 Ala499Val, exon 15 Lys939Gln on related risks to primary hepatocellular carcinoma (PHC)., Methods: A 1:1 matched case-control study was conducted in Shunde city, Guangdong province. The genotypes of Ala499Val and Lys939Gln were detected by polymerase chain reaction restrictive fragment length polymorphism (PCR-RFLP) analysis, and gene-environment interactions were analyzed by conditional logistic regression., Results: Among people infected by HBV with non- or at least one mutant gene of Ala499Val carriers, the risk of PHC significantly increased, with ORs as 3.768 (95%CI: 1.137 - 12.485) and 3.667(95%CI: 1.122 - 11.981) respectively. With non- or at least one mutant gene of Lys939Gln, the risk was increasing with ORs as 6.778 (95%CI: 2.025 - 22.688) and 3.152 (95%CI: 1.062 - 9.351) respectively. In those with HCV infection, non- or at least one mutant gene of Ala499Val might increase the risk with ORs as 2.955 (95%CI: 0.587 - 14.869), 1.085(95%CI: 0.307 - 3.839) respectively. However, when compared to the ones with no mutant gene of Lys939Gln among the same research subjects, those carrying at least one gene may decrease the risk, with OR lowered from 4.197 (95%CI: 0.870 - 20.243) to 0.887 (95%CI: 0.228 - 3.448). But the interactions between HBV infection, HCV infection and XPC genes were not statistically significant., Conclusion: Among people infected by HCV, the mutant gene of Ala499Val had the tendency to lower the risk of PHC, and the mutant gene of Lys939Gln also appeared the same in the population with either HBV infection or HCV infection in Shunde, Guangdong. Another study with large samples should be performed to analyze the interactions among environments-genes.

Objective: To study the correlation of polymorphisms of CYP1A1 MSPI and glutathiones S-transferase (GST-M1) independently and in combination with the risk of lung cancer., Methods: A case control study which included 91 cases of lung cancer and 138 controls collected from the First Affiliated Hospital of Sun Yat-sen University of Medical Sciences, Guangzhou Tumor Hospital and The Red Cross Hospital of Guangzhou or conmunity area. All subjects were investigated with a uniform questionnaire. Blood samples were collected from all cases and controls for detecting CYP1A1 MSPI and GST-M1 polymorphisms which were analyzed by PCR and RFLP., Results: It showed that there was no significant difference in frequencies of this genotypes of CYP1A1 MSPI between the two groups. The frequency of GST-M1 null (0/0) genotype was higher in the case group than in the control group, with an OR of 1.38 (95% CI 0.81 - 2.38), but there was no statistical significance. However, combination of several genotypes was strongly associated with lung cancer. There was a synergistic interaction between the m2m2 genotype of CYP1A1 MSPI and GST-M1 (0/0) genotype, with an OR of 2.47 (95% CI 1.03 - 5.90)., Conclusion: The combination of two genetic polymorphisms significantly increases the risk of lung cancer.

Objective: Serum p53 protein overexpression was detected in population exposed to traffic exhaust gas to study the relation between traffic exhaust gas and the increased risk in p53 gene mutation., Methods: Serum p53 protein expression was measured by enzyme-linked immunosorbent assay. Relationship between different types of job and serum p53 protein overexpression were studied by pearson Chi-square tests., Results: Results on serum p53 protein overexpression on jobs outside of office (5.74%) were not significantly higher than jobs inside the office. However, it suggested that traffic police men (12.12%) working outside of office, with whose length of service longer than 30 years had a significant overexpression of serum p53 protein than the others (5.36%) whose length of service was less than 30 years (P < 0.05, OR = 2.43, 95% CI: 1.11 - 5.33). Overexpression rate of p53 protein appeared to be 6.89% in the group whose average weekly exposure hours were more than 40 hours, which was significant higher than the group whose exposed hours were less than 40 hours (P < 0.05, OR = 1.71, 95% CI: 1.03 - 2.81)., Conclusion: The result suggested that traffic exhaust gas was likely to cause mutation of p53 gene and increasing the incidence of lung cancer.