| 1. |
- Catalano, Calogerina, et al.
(författare)
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Epistatic effect of TLR3 and cGAS-STING-IKKε-TBK1-IFN signaling variants on colorectal cancer risk
- 2020
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:4, s. 1473-1484
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The TLR3/cGAS-STING-IFN signaling has recently been reported to be disturbed in colorectal cancer due to deregulated expression of the genes involved. Our study aimed to investigate the influence of potential regulatory variants in these genes on the risk of sporadic colorectal cancer (CRC) in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Methods: The variants in the TLR3, CGAS, TMEM173, IKBKE, and TBK1 genes were selected using various online bioinformatic tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, SIFT, PolyPhen2, and miRNA prediction tools. Results: Logistic regression analysis adjusted for age and sex detected a nominal association between CRC risk and three variants, CGAS rs72960018 (OR: 1.68, 95% CI: 1.11-2.53, P-value =.01), CGAS rs9352000 (OR: 2.02, 95% CI: 1.07-3.84, P-value =.03) and TMEM173 rs13153461 (OR: 1.53, 95% CI: 1.03-2.27, P-value =.03). Their cumulative effect revealed a threefold increased CRC risk in carriers of 5-6 risk alleles compared to those with 0-2 risk alleles. Epistatic interactions between these genes and the previously genotyped IFNAR1, IFNAR2, IFNA, IFNB, IFNK, IFNW, IRF3, and IRF7 genes, were computed to test their effect on CRC risk. Overall, we obtained nine pair-wise interactions within and between the CGAS, TMEM173, IKBKE, and TBK1 genes. Two of them remained statistically significant after Bonferroni correction. Additional 52 interactions were observed when IFN variants were added to the analysis. Conclusions: Our data suggest that epistatic interactions and a high number of risk alleles may play an important role in CRC carcinogenesis, offering novel biological understanding for the CRC management.
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| 2. |
- Chattopadhyay, Subhayan, et al.
(författare)
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Prostate cancer survivors : Risk and mortality in second primary cancers
- 2018
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 7:11, s. 5752-5759
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Tidskriftsartikel (refereegranskat)abstract
- To assess etiological and clinical consequences of second primary cancers (SPCs) in prostate cancer (PC) patients, we followed newly diagnosed patients to identify men who were diagnosed with a SPC and recorded their causes of death. We used the Swedish Family-Cancer Database to assess relative risks (RRs) and causes of death in SPCs until the year 2015 in patients with a PC diagnosis between 2001 and 2010. Among a total of 4.26 million men, 76 614 were diagnosed with PC at the median age of 71 years. Among them, 8659 (11.3%) received a subsequent diagnosis of SPC after a median follow-up of 4 years. The most common SPCs were colorectal, skin, bladder, and lung cancers, melanoma, and non-Hodgkin lymphoma. The ranking was almost identical with first cancers among elderly men in Sweden. The RR for SPCs in prostate-specific antigen—detected PC was approximately equal to RR in other PC. Mortality patterns of PC patients were distinct depending on the presence or absence of SPC. Among patients with SPC, 47.8% died as a result of the corresponding SPC, followed by other causes (22.2%) and PC (18.1%). For patients without SPC, PC and non-neoplastic causes almost matched each other as the main causes of death (48.5% and 47.8%). The results suggest that SPCs appear autonomous from primary PC and reflect incidence and mortality of first cancers in general. SPC was the most common cause of death in patients with SPC; close to half of the patients died due to SPC. For improved survival in PC patients, prevention and early detection of SPCs would be important, and the present results suggest that risk factors for SPC in PC are the same as those for first cancer in general.
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| 3. |
- Zheng, Guoqiao, et al.
(författare)
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Rate differences between first and second primary cancers may outline immune dysfunction as a key risk factor
- 2020
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:21, s. 8258-8265
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many cancers are increased in immunosuppressed patients and evidence is accumulating that immune dysfunction may be a contributing risk factor for second primary cancers (SPCs). The aim of this study was to explore the potential influence of immune mechanisms in SPC. Methods: We used the Swedish Cancer Registry (1990-2015) to select 13 male and 14 female first primary cancers (FPCs) that are known to be related to immune suppression. We assessed relative risks (RRs) for any of these as concordant (same first and second cancer) and discordant FPC-SPC pairs. Hierarchical clustering of significant RRs was performed for cancers as FPC and SPC. Results: Concordant risks for SPCs were excessive in men and women for nasal (RRs 59.3 for men and 150.6 for women), tongue/mouth (51.7 and 100.8), and lip (32.4 and 61.2) cancers. Heatmaps showed that some cancers, such as skin cancer, tongue/mouth cancers, and non-Hodgkin lymphoma had multiple bidirectional associations as FPC and SPC. Nasal cancer and chronic lymphocytic leukemia had associations mainly as FPC while liver and kidney cancers showed most associations as SPC. Conclusions: Immune dysfunction may be a plausible contributing factor for most of the associations, which calls for experimental verification.
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| 4. |
- Zheng, Guoqiao, et al.
(författare)
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Second primary cancer after female breast cancer : Familial risks and cause of death
- 2019
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 8:1, s. 400-407
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Tidskriftsartikel (refereegranskat)abstract
- Background: With continuous increases in survival rates following breast cancer (BC) diagnosis, the challenge of multiple primary cancers has become an issue. The data on familial risk of SPCs after BC diagnosis and the related mortality in BC patients are scarce. Methods: A total of 87 752 female BC patients were followed for SPC diagnoses and records of death. Relative risks (RRs) of SPC in BC patients who had first-degree relatives (parents or siblings) affected by the same cancer were compared to the patients without family history. Causes of death were compared between patients with and without SPC. Results: After a median follow-up of 5 years, 14 952 BC patients developed SPCs, among which 10 280 (68.8%) had first-degree relatives diagnosed with cancer. Familial risks were significant for 14 site-specific SPCs, and the highest risk was for second ovarian cancer (RR = 6.28, 95%CI: 4.50-8.75), compared to those without family history (1.49, 1.34-1.65). In patients with SPC, SPC was the main cause of death, including diverse cancers and BC in approximately equal proportions. Conclusions: Family history contributed to the excess number of patients with SPCs, and SPC was the leading cause of death in patients with SPC. Taking family history at diagnosis of BC may provide warning signs with regard to possible subsequent SPCs and may offer possibilities for counseling, intervention and management.
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