scholarly journals Germline genomic patterns are associated with cancer risk, oncogenic pathways and clinical outcomes

2019 ◽  
Author(s):  
Xiaowen Feng ◽  
Xue Xu ◽  
Derek Li ◽  
Qinghua Cui ◽  
Edwin Wang
Keyword(s):  
Cancer Risk ◽  
Clinical Outcomes ◽  
Genome Instability ◽  
Cancer Risks ◽  
Systematic Analysis ◽  
Common Cancer ◽  
Oncogenic Pathways ◽  
Cancer Types ◽  
Genomic Patterns ◽  
Present Gene

SummaryGermline genetic polymorphism is prevalent and inheritable. So far mutations of a handful of genes have been associated with cancer risks. For example, women who harbor BRCA1/2 germline mutations have a 70% of cumulative breast cancer risk; individuals with congenital germline APC mutations have nearly 100% of cumulative colon cancer by the age of fifty. At present, gene-centered cancer predisposition knowledge explains only a small fraction of the inheritable cancer cases. Here we conducted a systematic analysis of the germline genomes of cancer patients (n=9,712) representing 22 common cancer types along with non-cancer individuals (n=16,670), and showed that seven germline genomic patterns, or significantly repeatedly occurring sequential mutation profiles, could be associated with both carcinogenesis processes and cancer clinical outcomes. One of the genomic patterns was significantly enriched in the germline genomes of patients who smoked than in those of non-smoker patients of 13 common cancer types, suggesting that the germline genomic pattern was likely to confer an elevated carcinogenesis sensitivity to tobacco smoke. Several patterns were also associated with somatic mutations of key oncogenic genes and somatic-mutational signatures which are associated with higher genome instability in tumors. Furthermore, subgroups defined by the germline genomic patterns were significantly associated with distinct oncogenic pathways, tumor histological subtypes and prognosis in 12 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results demonstrated that genetic cancer risk and clinical outcomes could be encoded in germline genomes in the form of not only mutated genes, but also specific germline genomic patterns, which provided a novel perspective for further investigation.

scholarly journals Germline genomic patterns are associated with cancer risk, oncogenic pathways, and clinical outcomes

2020 ◽  
Vol 6 (48) ◽  
pp. eaba4905
Author(s):  
Xue Xu ◽  
Yuan Zhou ◽  
Xiaowen Feng ◽  
Xiong Li ◽  
Mohammad Asad ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Clinical Outcomes ◽  
Genome Instability ◽  
Ongoing Debate ◽  
Systematic Analysis ◽  
Mutational Spectra ◽  
Common Cancer ◽  
Oncogenic Pathways ◽  
Cancer Types ◽  
Genomic Patterns

There is an ongoing debate on the importance of genetic factors in cancer development, where gene-centered cancer predisposition seems to show that only 5 to 10% of the cancer cases are inheritable. By conducting a systematic analysis of germline genomes of 9712 cancer patients representing 22 common cancer types along with 16,670 noncancer individuals, we identified seven cancer-associated germline genomic patterns (CGGPs), which summarized trinucleotide mutational spectra of germline genomes. A few CGGPs were consistently enriched in the germline genomes of patients whose tumors had smoking signatures or correlated with oncogenesis- and genome instability–related mutations. Furthermore, subgroups defined by the CGGPs were significantly associated with distinct oncogenic pathways, tumor histological subtypes, and prognosis in 13 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results provided evidence that cancer risk and clinical outcomes could be encoded in germline genomes.

Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers

2016 ◽  
Vol 76 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Karin Hellgren ◽  
Lene Dreyer ◽  
Elizabeth V Arkema ◽  
Bente Glintborg ◽  
Lennart T H Jacobsson ◽  
...  
Keyword(s):  
General Population ◽  
Collaborative Study ◽  
Safety Data ◽  
Cancer Risks ◽  
Common Cancer ◽  
National Patient ◽  
Spa Treatment ◽  
Cancer Types ◽  
Factor Α ◽  
Necrosis Factor

BackgroundSafety data on cancer risks following tumour necrosis factor α inhibitors (TNFi) in patients with spondyloarthritis (SpA) (here defined as ankylosing spondylitis (AS), undifferentiated spondarthropaties (SpA UNS), psoriatic arthritis (PsA)) are scarce. Our objective was to assess risks for cancer overall and for common subtypes in patients with SpA treated with TNFi compared with TNFi-naïve patients with SpA and to the general population.MethodsFrom the Swedish (Anti-Rheumatic Therapy in Sweden (ARTIS)) and Danish (DANBIO) biologics registers, we assembled 8703 (ARTIS=5448, DANBIO=3255) patients with SpA initiating a first TNFi 2001–2011. From the Swedish National Patient and Population Registers we assembled a TNFi-naïve SpA cohort (n=28,164) and a Swedish age-matched and sex-matched general population comparator cohort (n=131 687). We identified incident cancers by linkage with the nationwide Swedish and Danish Cancer Registers 2001–2011, and calculated age-standardised and sex-standardised incidence ratios as measures of relative risk (RR).ResultsBased on 1188 cancers among the TNFi-naïve patients with SpA, RR of cancer overall was 1.1 (95% CI 1.0 to 1.2). Based on 147 cancers among TNFi initiators with SpA, RR versus TNFi-naïve was 0.8 (95% CI 0.7 to 1.0) and results were similar for AS and PsA when analysed separately. Site-specific cancer RRs: prostate 0.5 (95% CI 0.3 to 0.8), lung 0.6 (95% CI 0.3 to 1.3), colorectal 1.0 (95% CI 0.5 to 2.0), breast 1.3 (95% CI 0.9 to 2.0), lymphoma 0.8 (95% CI 0.4 to 1.8) and melanoma 1.4 (95% CI 0.7 to 2.6).ConclusionsIn patients with SpA, treatment with TNFi was not associated with increased risks of cancer, neither overall nor for the six most common cancer types.

scholarly journals Antibiotic exposure is associated with an increased risk of cancer: a systematic review and meta-analysis

2019 ◽  
Author(s):  
Yuting Li ◽  
Kaiyin He ◽  
Xiaojuan Peng ◽  
Chenxing Zhang ◽  
Lu Zhong ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Meta Analysis ◽  
Antibiotic Use ◽  
Epidemiological Studies ◽  
Antibiotic Exposure ◽  
Time Restrictions ◽  
Common Cancer ◽  
Increased Risk ◽  
Cancer Types ◽  
Risk Of Cancer

Abstract Background Several epidemiological studies have assessed the association between the use of antibiotics and cancer risk, but the results were inconsistent. Objective The objective of this study was to perform a meta-analysis to further evaluate possible association between antibiotic exposure and the risk of cancer. Methods We searched PubMed,Embase,Web of Science,and Chinese databases for studies on the association between antibiotic use and cancer without time restrictions. The risk estimates (hazard ratio (HR) or relative risk (RR) or Odds ratio (OR)) with their corresponding 95% confidence interval (CI) were calculated. Results A total of 23 observational studies with 19 case-control and 4 cohort studies were included in the meta-analysis. Exposure to antibiotics significantly increased the risk of cancer with an OR of 1.20 (95%CI 1.13-1.27, P=0.000). Subgroup meta-analysis by gender showed that the effect of antibiotic use on cancer risk was greater in male (34%) compared with that in female (19%). On the other hand, the risk of cancer increased with an increasing number of antibiotic prescriptions and the increasing cumulative days of antibiotic exposure. Moreover, of the 7 antibiotic types included, the six classes of antibiotics (penicillin, macrolides, quinolones, sulfonamides, tetracycline, cephalosporins) were associated with the increased risk of cancer. Further, of the 16 separate cancers included, exposure to antibiotics increased the risk of eight common cancer types (liver cancer, colorectal cancer, stomach and small intestine cancer, lymphomas, breast cancer, lung cancer, prostate cancer, and renal and bladder). Conclusions Exposure to common antibiotic types may increase the risk of the eight common cancer types in the studies population, especially in male, and the cancer risk increases with increasing antibiotic exposure intensity.

scholarly journals A Matrix Metalloproteinase-1 Polymorphism,MMP1–1607(1G>2G), Is Associated with Increased Cancer Risk: A Meta-Analysis Including 21,327 Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Zhonghan Zhou ◽  
Xiaocheng Ma ◽  
Fangming Wang ◽  
Lijiang Sun ◽  
Guiming Zhang
Keyword(s):  
Cancer Risk ◽  
Matrix Metalloproteinase ◽  
Meta Analysis ◽  
Recessive Model ◽  
Elevated Risk ◽  
Cancer Risks ◽  
Matrix Metalloproteinase 1 ◽  
The Matrix ◽  
Cancer Types ◽  
Allele Model

Although the matrix metalloproteinase-1 (MMP1) polymorphismMMP1–1607 (1G>2G) has been associated with susceptibility to various cancers, these findings are controversial. Therefore, we conducted this meta-analysis to explore the association betweenMMP1–1607 (1G>2G) and cancer risk. A systematic search of literature through PubMed, Embase, ISI Web of Knowledge, and Google Scholar yielded 77 articles with 21,327 cancer patients and 23,245 controls. The association between theMMP1–1607 (1G>2G) polymorphism and cancer risks was detected in an allele model (2G vs. 1G, overall risk [OR]: 1.174, 95% confidence interval [CI]: 1.107–1.244), a dominant model (2G2G/1G2G vs. 1G1G OR, OR: 1.192, 95% CI: 1.090–1.303), and a recessive model (2G2G vs. 1G2G/1G1G, OR: 1.231, 95% CI: 1.141–1.329). In subgroup analysis, these associations were detected in both Asians and Caucasians. After stratification by cancer types, associations were found in lung, colorectal, nervous system, renal, bladder, and nasopharyngeal cancers. This meta-analysis revealed thatMMP1–1607 (1G>2G) polymorphism was significantly associated with elevated risk of cancers.

scholarly journals Spectrum and Frequency of Tumors, Cancer Risk and Survival in Chilean Families with Lynch Syndrome: Experience of the Implementation of a Registry

2020 ◽  
Vol 9 (6) ◽  
pp. 1861
Author(s):  
Karin Álvarez ◽  
Paulina Orellana ◽  
Marjorie De la Fuente ◽  
Tamara Canales ◽  
Eliana Pinto ◽  
...  
Keyword(s):  
At Risk ◽  
Latin America ◽  
Cancer Risk ◽  
Lynch Syndrome ◽  
Genetic Counselling ◽  
Cumulative Incidence ◽  
Cancer Risks ◽  
Diagnostic Practice ◽  
Common Cancer ◽  
Extracolonic Cancers

Lynch syndrome (LS) is associated with the highest risk of colorectal (CRC) and several extracolonic cancers. In our effort to characterize LS families from Latin America, this study aimed to describe the spectrum of neoplasms and cancer risk by gender, age and gene, and survival in 34 Chilean LS families. Of them, 59% harbored path_MLH1, 23% path_MSH2, 12% path_PMS2 and 6% path_EPCAM variants. A total of 866 individuals at risk were identified, of which 213 (24.6%) developed 308 neoplasms. In males, CRC was the most common cancer (72.6%), while females showed a greater frequency of extracolonic cancers (58.4%), including uterus and breast (p < 0.0001). The cumulative incidence of extracolonic cancers was higher in females than males (p = 0.001). Path_MLH1 variants are significantly more associated with the development of CRC than extracolonic tumors (59.5% vs. 40.5%) when compared to path_MSH2 (47.5% vs. 52.5%) variants (p = 0.05018). The cumulative incidence of CRC was higher in path_MLH1/path_MSH2 carriers compared to path_PMS2 carriers (p = 0.03). In addition, path_MSH2 carriers showed higher risk of extracolonic tumors (p = 0.002). In conclusion, this study provides a snapshot of the LS profile from Chile and the current LS-associated diagnostic practice and output in Chile. Categorizing cancer risks associated with each population is relevant in the genetic counselling of LS patients.

scholarly journals Statistical meta-analysis to investigate the association between the Interleukin-6 (IL-6) gene polymorphisms and cancer risk

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247055
Author(s):  
Md. Harun-Or-Roshid ◽  
Md. Borqat Ali ◽  
Jesmin ◽  
Md. Nurul Haque Mollah
Keyword(s):  
Cancer Risk ◽  
Statistical Modeling ◽  
Subgroup Analysis ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Cancer Risks ◽  
Increased Risk ◽  
Cancer Types ◽  
Meta Analyses

A good number of genome-wide association studies (GWAS), including meta-analyses, reported that single nucleotide polymorphisms (SNPs) of the IL-6 gene are significantly associated with various types of cancer risks, though some other studies reported insignificant association with cancers, in the literature. These contradictory results may be due to variations in sample sizes and/or deficiency of statistical modeling. Therefore, an attempt is made to provide a more comprehensive understanding of the association between the IL-6 gene SNPs (rs1800795, rs1800796, rs1800797) and different cancer risks, giving the weight on a large sample size, including different cancer types and appropriate statistical modeling with the meta-dataset. In order to attain a more reliable consensus decision about the association between the IL-6 gene polymorphisms and different cancer risks, in this study, we performed a multi-case statistical meta-analysis based on the collected information of 118 GWAS studies comprising of 50053 cases and 65204 control samples. Results from this Meta-analysis indicated a significant association (p-value < 0.05) of the IL-6 gene rs1800796 polymorphism with an overall increased cancer risk. The subgroup analysis data based on cancer types exhibited significant association (p-value < 0.05) of the rs1800795 polymorphism with an overall increased risk of cervical, liver and prostate cancers; the rs1800796 polymorphism with lung, prostate and stomach cancers; and the rs1800797 polymorphism with cervical cancer. The subgroup analysis of ethnicity data showed a significant association (p-value < 0.05) of an overall cancer risk with the rs1800795 polymorphism for the African and Asian populations, the rs1800796 polymorphism for the Asian only and the rs1800797 polymorphism in the African population. Comparative discussion showed that our multi-case meta-analyses received more support than any previously reported individual meta-analysis about the association between the IL-6 gene polymorphisms and cancer risks. Results from this study, more confidently showed that the IL-6 gene SNPs (rs1800795, rs1800796 and rs1800797) in humans are associated with increased cancer risks. Therefore, these three polymorphisms of the IL-6 gene have the potential to be evaluated as a population based rapid, low-cost PCR prognostic biomarkers for different types of cancers diagnosis and research.

scholarly journals Histone Modifying Enzymes in Gynaecological Cancers

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 816
Author(s):  
Priya Ramarao-Milne ◽  
Olga Kondrashova ◽  
Sinead Barry ◽  
John D. Hooper ◽  
Jason S. Lee ◽  
...  
Keyword(s):  
Genome Instability ◽  
Cpg Islands ◽  
Gene Promoter ◽  
Driver Mutations ◽  
Promoter Regions ◽  
Post Translational Modifications ◽  
Chromatin Dynamics ◽  
Cancer Types ◽  
Histone Modifying Enzymes

Genetic and epigenetic factors contribute to the development of cancer. Epigenetic dysregulation is common in gynaecological cancers and includes altered methylation at CpG islands in gene promoter regions, global demethylation that leads to genome instability and histone modifications. Histones are a major determinant of chromosomal conformation and stability, and unlike DNA methylation, which is generally associated with gene silencing, are amenable to post-translational modifications that induce facultative chromatin regions, or condensed transcriptionally silent regions that decondense resulting in global alteration of gene expression. In comparison, other components, crucial to the manipulation of chromatin dynamics, such as histone modifying enzymes, are not as well-studied. Inhibitors targeting DNA modifying enzymes, particularly histone modifying enzymes represent a potential cancer treatment. Due to the ability of epigenetic therapies to target multiple pathways simultaneously, tumours with complex mutational landscapes affected by multiple driver mutations may be most amenable to this type of inhibitor. Interrogation of the actionable landscape of different gynaecological cancer types has revealed that some patients have biomarkers which indicate potential sensitivity to epigenetic inhibitors. In this review we describe the role of epigenetics in gynaecological cancers and highlight how it may exploited for treatment.

scholarly journals Gastric microbiota features associated with cancer risk factors and clinical outcomes: A pilot study in gastric cardia cancer patients from Shanxi, China

2017 ◽  
Vol 141 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Guoqin Yu ◽  
Nan Hu ◽  
Lemin Wang ◽  
Chaoyu Wang ◽  
Xiao-You Han ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pilot Study ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Gastric Cardia ◽  
Cardia Cancer ◽  
Cancer Risk Factors ◽  
Gastric Cardia Cancer ◽  
Gastric Microbiota

Genes, Cancer Risks, and Clinical Outcomes

2007 ◽  
Vol 357 (2) ◽  
pp. 175-176 ◽  
Author(s):  
Patricia Hartge
Keyword(s):  
Clinical Outcomes ◽  
Cancer Risks
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