scholarly journals Outcome Definition Influences the Relationship between Genetic Polymorphisms of ERCC1, ERCC2, SLC22A2 and Cisplatin Nephrotoxicity in Adult Testicular Cancer Patients

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 364 ◽  
Author(s):  
Zulfan Zazuli ◽  
Leila S. Otten ◽  
Britt I. Drögemöller ◽  
Mara Medeiros ◽  
Jose G. Monzon ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Cancer Patients ◽  
Genetic Polymorphisms ◽  
Estimated Glomerular Filtration Rate ◽  
Kidney Injury ◽  
Case Definitions ◽  
Cisplatin Nephrotoxicity ◽  
Increased Risk ◽  
The Relationship ◽  
Relevant Outcome

Although previous research identified candidate genetic polymorphisms associated with cisplatin nephrotoxicity, varying outcome definitions potentially contributed to the variability in the effect size and direction of this relationship. We selected genetic variants that have been significantly associated with cisplatin-induced nephrotoxicity in more than one published study (SLC22A2 rs316019; ERCC1 rs11615 and rs3212986; ERCC2 rs1799793 and rs13181) and performed a replication analysis to confirm associations between these genetic polymorphisms and cisplatin nephrotoxicity using various outcome definitions. We included 282 germ cell testicular cancer patients treated with cisplatin from 2009–2014, aged >17 years recruited by the Canadian Pharmacogenomics Network for Drug Safety. Nephrotoxicity was defined using four grading tools: (1) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 for acute kidney injury (AKI) or CTCAE-AKI; (2) adjusted cisplatin-induced AKI; (3) elevation of serum creatinine; and (4) reduction in the estimated glomerular filtration rate (eGFR). Significant associations were only found when using the CTCAE v4.03 definition: genotype CA of the ERCC1 rs3212986 was associated with decreased risk of cisplatin nephrotoxicity (ORadj = 0.24; 95% CI: 0.08–0.70; p = 0.009) compared to genotype CC. In contrast, addition of allele A at SLC22A2 rs316019 was associated with increased risk (ORadj = 4.41; 95% CI: 1.96–9.88; p < 0.001) while genotype AC was associated with a higher risk of cisplatin nephrotoxicity (ORadj = 5.06; 95% CI: 1.69–15.16; p = 0.004) compared to genotype CC. Our study showed that different case definitions led to variability in the genetic risk ascertainment of cisplatin nephrotoxicity. Therefore, consensus on a set of clinically relevant outcome definitions that all such studies should follow is needed.

scholarly journals Relationship between clinical toxicities and ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms in cervical cancer patients

2017 ◽  
Vol 33 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Sílvia Soares ◽  
Augusto Nogueira ◽  
Ana Coelho ◽  
Joana Assis ◽  
Deolinda Pereira ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Genetic Polymorphisms ◽  
Recessive Model ◽  
Gastrointestinal Toxicity ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination ◽  
Homozygous Genotype ◽  
Increased Risk ◽  
The Relationship

Background: Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be considered potential biomarkers in the prognosis and therapeutic response of cancer patients. The present study investigated the association between ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms and clinical toxicities induced by chemoradiotherapy (CRT) in cervical cancer. Methods: This hospital-based retrospective cohort study included 260 patients with cervical cancer, FIGO stages Ib2-IVa, who underwent CRT (cisplatin). Genetic polymorphisms analysis was performed by allelic discrimination with real-time polymerase chain reaction (RT-PCR). Results: Our results indicated a link between ERCC1 rs3212986 and the onset of late gastrointestinal toxicity (p = 0.038). Furthermore, using a recessive model (AA vs. CC/CA), we found that patients carrying AA homozygous genotype presented a fourfold increased risk of developing late gastrointestinal toxicity when compared with patients with the C allele (odds ratio = 3.727, 95% confidence interval, 1.199-11.588; p = 0.017). No association was found regarding the XRCC3 rs861539 polymorphism and any clinical toxicity event. Conclusions: This is the first study evaluating the relationship between these polymorphisms and clinical toxicities in cervical cancer patients submitted to CRT with cisplatin. These results may contribute toward a better understanding of the influence of genetic polymorphisms in genes associated with DNA repair in the clinical response to CRT of patients with cervical cancer.

scholarly journals Ethnicity-Stratified Analysis of the Association between TNF-α Genetic Polymorphisms and Acute Kidney Injury: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Guanzhong Chen ◽  
Bowen Liu ◽  
Huanqiang Li ◽  
Ziling Mai ◽  
Liyao Zhang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Genetic Polymorphisms ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Asian Population ◽  
Necrosis Factor Alpha ◽  
Increased Risk ◽  
Tnf Α ◽  
Stratified Analysis ◽  
The Relationship

Background. Several studies have reported conflicting findings regarding the association between tumor necrosis factor-alpha (TNF-α) genetic polymorphisms and acute kidney injury (AKI). Therefore, we performed this meta-analysis to further investigate whether TNF-α variants are related to AKI susceptibility. Methods. A comprehensive search of observational studies on the association of TNF-α polymorphism with AKI susceptibility was conducted in the PubMed, Cochrane, and Embase databases through February 10, 2020. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (95% CIs) were analyzed to evaluate the strength of the relationship. Results. A total of 8 studies involving 6694 patients (2559 cases and 4135 controls) were included. Pooled analysis showed a trend of increased risk between the TNF-α rs1800629 variant and AKI (A vs. G: OR   95 % CI = 1.33   0.98 ‐ 1.81 ) among the overall population. Ethnicity-stratified analysis indicated that the TNF-α rs1800629 variant was a risk factor for Asians ( OR   95 % CI = 1.93   1.59 ‐ 2.35 ) while it is not for Caucasians ( OR   95 % CI = 1.04   0.91 ‐ 1.20 ). Additionally, we also found that TNF-α rs1799964 polymorphism was observed to have a significant relationship with AKI risk in Asian patients (C vs. T, OR   95 % CI = 1.26   1.11 ‐ 1.43 ). Conclusions. The TNF rs1800629 polymorphism exhibited a trend toward AKI susceptibility with ethnic differences. The relationship was found to be significant among the Asian population, but not among those of Caucasian origin. Additionally, the TNF-α rs1799964 polymorphism was also related to a significantly increased risk of AKI in Asians.

scholarly journals Depression and Fatigue of Breast Cancer Patients Receiving Chemotherapy during the Covid-19

2021 ◽  
Vol 3 (3) ◽  
pp. 297-304
Author(s):  
Dwi Retnaningsih ◽  
Roudhotul Auliyak ◽  
Mariyati Mariyati ◽  
Enggar Nurnaningsih
Keyword(s):  
Breast Cancer ◽  
Data Analysis ◽  
Cancer Patients ◽  
Depression Scale ◽  
Fear Of Death ◽  
Anxiety And Depression ◽  
P Value ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
The Relationship

Depression in breast cancer patients includes mental shock, inability to accept reality, hopelessness, fear of death, and fear of the future. Depression creates long periods of sadness and worry, usually accompanied by feelings of worthlessness. Fatigue is a symptom that often appears in cancer patients undergoing chemotherapy. Associated with the conditions of the COVID-19 pandemic, cancer patients have an increased risk of transmitting COVID-19 because they have decreased endurance. This study aims to determine the relationship between depression and fatigue in breast cancer patients undergoing chemotherapy at Hospital Sultan Agung Semarang Indonesia. The instruments used in this study were questionnaire of the hospitals anxiety and Depression Scale (HADS) and questionnaire of fatigue, 30 female respondents who suffer from breast cancer and have undergone chemotherapy. Rank Spearman data analysis. P value = 0.000 and correlation coefficient value r = 0.671. There is a relationship between depression and fatigue in breast cancer patients undergoing chemotherapy which has an impact on adherence to chemotherapy for breast cancer patients. The higher the level of depression is, the more severe the level of fatigue in cancer patients.

scholarly journals NGAL, albumin and cystatin C during cisplatin therapy

2020 ◽  
pp. 307-317
Author(s):  
B. Florova ◽  
D. Rajdl ◽  
J. Racek ◽  
O. Fiala ◽  
V. M. Matejka ◽  
...  
Keyword(s):  
Cystatin C ◽  
Kidney Injury ◽  
Cumulative Effect ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Cisplatin Nephrotoxicity ◽  
Urine Albumin ◽  
Increased Risk ◽  
Neutrophil Gelatinase

Cisplatin is a commonly used chemotherapeutic drug. It is known for its nephrotoxic side effects with an increased risk of acute kidney injury. Finding of clinically feasible cisplatin nephrotoxicity markers is of importance. In our study, we compared neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine, the estimated glomerular filtration rate (based on serum cystatin C) and urine albumin as markers of nephrotoxicity. The study involved 11 men and 9 women (mean ± SD age 58.2 ± 9.5 years) with different malignancies treated with cisplatin in four cycles of chemotherapy (I – IV). Samples 0 4 were taken before, immediately after, in 3, 6 and 24 hours after administering chemotherapy. We detected significant increase of ACR in Sample 2 (p=0.03) and decrease of eGFR in Sample 4 (p=0.03) up to 24 hours after cisplatin administration in the first chemotherapy cycle only. When cumulative effect of cisplatin was assessed, significantly increased values of urine albumin (vs cycle I) were found in Sample 0 (p=0.00058), 1 (p=0.00256), 2 (p=0.00456), 3 (p=0.00006) and 4 (p=0.00319) in cycles II to IV. We found a correlation between values of urine NGAL and urine albumin (r=0.68, p<0.0001). In conclusion, urine albumin was the only measured marker that consistently and statistically significantly increased after cisplatin containing chemotherapy cycles.

Incidence of acute kidney injury in cancer patients: A population-based cohort study in Denmark

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9570-9570
Author(s):  
C. F. Christiansen ◽  
M. B. Johansen ◽  
S. Christensen ◽  
W. Langeberg ◽  
J. P. Fryzek ◽  
...  
Keyword(s):  
At Risk ◽  
Multiple Myeloma ◽  
Acute Kidney Injury ◽  
Cohort Study ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Kidney Injury ◽  
Population Based ◽  
First Year ◽  
Increased Risk

9570 Background: Although cancer patients may be at increased risk for acute kidney injury (AKI), which could then reduce their likelihood of receiving optimal therapeutic management and supportive care, the occurrence of AKI among newly diagnosed cancer patients has not been well-described. Therefore, we examined the incidence of AKI within the first year after cancer diagnosis to estimate the magnitude of this risk and better understand which patients are at greatest risk. Methods: Using the population-based Danish Cancer Registry, we conducted a retrospective cohort study of 4,427 men and women from North Jutland, Denmark (population 500,000) diagnosed with cancer from 2002 to 2003 (non-melanoma skin cancer excluded). AKI was defined according to the Risk/ Injury/ Failure/ Loss/ End-stage-renal-disease (RIFLE) criteria. We included Risk or worse: at least a 1.5 times increase in serum creatinine (sCr) from baseline. SCr levels were obtained from the Regional Laboratory Database, which collects all biochemical analyses for hospital laboratories. Baseline sCr was defined as the lowest sCr in the year before cancer diagnosis. We compared this value to the highest sCr on record during the first year following cancer diagnosis to identify those who experienced an AKI. Results: Median age for the cohort was 68.6 years, 50.9% were men, and the most common cancer sites were lung (14.2%), breast (13.7%), prostate (9.8%), colon (9.6%), rectum (5.1%), and bladder (6.3%). During the first year, 973 (22.0%) members of the cohort experienced an AKI, corresponding to an overall incidence rate of 326 per 1,000 person-years (95% confidence interval (CI) 306–347). Incidence was highest among patients aged 80 years or older (531 per 1,000 person-years, 95% CI 464–606) and in those with cancer of the liver (1,221, 95%CI 676–2,205), pancreas (1,472, 95%CI 1,130–1,917), or kidney (1,254, 95%CI 974–1,616), or with multiple myeloma (855, 95%CI 538–1,356). Conclusions: To protect against AKI, we must first identify those at risk. Our study showed that over 20% of cancer patients may experience acute kidney injury in the first year after diagnosis. Older patients and those with cancer of the liver, pancreas, or kidney, or with multiple myeloma are especially at risk for AKI. [Table: see text]

Relationship of testicular cancer incidence and cellular phone use.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12008-e12008
Author(s):  
Robert A. Somer ◽  
Rakesh Surapaneni ◽  
Douglas Francis Beach
Keyword(s):  
United States ◽  
Testicular Cancer ◽  
Cell Phone ◽  
Incidence Rates ◽  
World Health ◽  
Percentage Increase ◽  
Cancer Data ◽  
Increased Risk ◽  
Relationship Of ◽  
The Relationship

e12008 Background: Because of the ubiquitous usage of cellphones, any health consequences, if found, would be of paramount importance. Many have questioned the relationship of cellphone radiofrequency waves and malignancies such as brain tumors. Because men usually store their phones in close proximately to the testicles, we analyzed the relationship between cell phone usage and testicular cancer. Methods: Testicular cancer data was obtained from SEER-9 United States Population Data Base of the National Cancer Institute. Cell phone subscription data was obtained from the World Health Organization publication. Initial data analysis was done from 1991 to 2008, with subsequent age specific and other analyses performed from 1999 to 2008. Trends over time were calculated as Annual Percentage Change of incidence rates (APC) by using log linear models. Results: Rates of United States mobile subscriptions increased exponentially since the late 1990’s reaching 88.87 percent of the population by 2008. There was no statistically significant change in incidence rates of all testicular tumors (APC 0.7; CI -0.2, 0.7), Seminoma (APC 0.2; CI 0.8, 1.1) and non-Seminoma (APC 1.4; CI -0.6, 3.4) from 1999 to 2008. In the age specific analysis, three groups showed an increase in incidence rates: all testicular cancer age 25-34 (APC 2; CI 0.6, 3.4), All testicular cancer age greater than 45 (APC 1.7; CI 0.1, 3.3) and Seminoma age 25-34 (APC 2.1; CI 0.6, 3.7). All these changes were only minor percentage increase when compared to mobile subscriptions. Conclusions: Based on incidence data, there is no convincing evidence of increased risk of testicular cancer from cell phone use. Given possible lag time incidence, continued monitoring is needed.

scholarly journals Association of UGT1A1*6,*28 or ABCC2 c.3972C>T genetic polymorphisms with irinotecan induced toxicity in Asian cancer patients: Meta-analysis

2021 ◽  
Author(s):  
Chalirmporn Atasilp ◽  
Mohitosh Biswas ◽  
Pimonpan Jinda ◽  
Nutthan Nuntharadthanaphong ◽  
Jiratha Rachanakul ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Genetic Polymorphisms ◽  
Genetic Variants ◽  
Genetic Variant ◽  
Meta Analysis ◽  
Odds Ratios ◽  
P Values ◽  
Increased Risk

Abstract: Background: Effects of UGT1A1*6 and UGT1A1*28 genetic polymorphisms on irinotecan-induced severe toxicities in Asian cancer patients are inconclusive. Also, ABCC2 c.3972C>T may affect toxicity of irinotecan. It was aimed to assess the aggregated risk of neutropenia or diarrhea in Asian cancer patients taking irinotecan and inherited UGT1A1*6, UGT1A1*28 or ABCC2 c.3972C>T genetic variants. Methods: Literature was searched in PubMed for eligible studies. Odds ratios (ORs) were measured using RevMan software where P-values<0.05 were statistically significant. Results: Patients inherited both UGT1A1*6 and UGT1A1*28 genetic variants (heterozygous:UGT1A1*1/*6+*1/*28 and homozygous:UGT1A1*6/*6+*28/*28) were significantly associated with increased risk of neutropenia and diarrhea compared to patients with UGT1A1*1/*1 (Neutropenia: OR 2.89; 95% CI 1.97–4.23; P<0.00001; Diarrhea: OR 2.26; 95% CI 1.71–2.99; P<0.00001). Patients carried homozygous variants had much stronger effects in developing toxicities (Neutropenia: OR 6.23; 95% CI 3.11–12.47; P<0.00001; Diarrhea: OR 3.21; 95% CI 2.13–4.85; P<0.00001) than with heterozygous variants. However, patients carried ABCC2 c.3972C>T genetic variant were not significantly associated with neutropenia (OR 1.67; 95% CI 0.98–2.84; P=0.06) but reduced diarrhea significantly (OR 0.31; 95% CI 0.11–0.81; P=0.02). Conclusions: Both UGT1A1*6 and UGT1A1*28 genetic variants should screen in Asian cancer patients to reduce substantially irinotecan-induced severe toxicities.

scholarly journals Acute Kidney Injury Classified by Serum Creatinine and Urine Output in Critically Ill Cancer Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Bertha M. Córdova-Sánchez ◽  
Ángel Herrera-Gómez ◽  
Silvio A. Ñamendys-Silva
Keyword(s):  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Cancer Patients ◽  
Critically Ill ◽  
Urine Output ◽  
Cohort Analysis ◽  
Kidney Injury ◽  
Risk Of Death ◽  
Increased Risk ◽  
Stage 1

Acute kidney injury (AKI) is common in critically ill patients and is associated with higher mortality. Cancer patients are at an increased risk of AKI. Our objective was to determine the incidence of AKI in our critically ill cancer patients, using the criteria of serum creatinine (SCr) and urine output (UO) proposed by the Kidney Disease: Improving Global Outcomes (KDIGO).Methods.We performed a retrospective cohort analysis of a prospectively collected database at the intensive care unit (ICU) of the Instituto Nacional de Cancerología from January 2013 to March 2015.Results.We classified AKI according to the KDIGO definition. We included 389 patients; using the SCr criterion, 192 (49.4%) had AKI; using the UO criterion, 219 (56.3%) had AKI. Using both criteria, we diagnosed AKI in 69.4% of patients. All stages were independently associated with six-month mortality; stage 1 HR was 2.04 (95% CI 1.14–3.68,p=0.017), stage 2 HR was 2.73 (95% CI 1.53–4.88,p=0.001), and stage 3 HR was 4.5 (95% CI 2.25–8.02,p<0.001). Patients who fulfilled both criteria had a higher mortality compared with patients who fulfilled just one criterion (HR 3.56, 95% CI 2.03–6.24,p<0.001).Conclusion.We diagnosed AKI in 69.4% of patients. All AKI stages were associated with higher risk of death at six months, even for patients who fulfilled just one AKI criterion.

scholarly journals An Association Between Hyperchloremia and Acute Kidney Injury in Patients With Acute Ischemic Stroke

2020 ◽  
Vol 10 (4) ◽  
pp. 250-256
Author(s):  
J. Tyler Haller ◽  
Keaton Smetana ◽  
Michael J. Erdman ◽  
Todd A. Miano ◽  
Heidi M. Riha ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Ischemic Stroke ◽  
Length Of Stay ◽  
Acute Ischemic Stroke ◽  
Kidney Injury ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Matched Cohort ◽  
Increased Risk ◽  
The Relationship

Background and Purpose: While an association between hyperchloremia and worse outcomes, such as acute kidney injury and increased mortality, has been demonstrated in hemorrhagic stroke, it is unclear whether the same relationship exists after acute ischemic stroke. This study aims to determine the relationship between moderate hyperchloremia (serum chloride ≥115 mmol/L) and acute kidney injury in patients with ischemic stroke. Methods: This is a multicenter, retrospective, propensity-matched cohort study of adults admitted for acute ischemic stroke. The primary objective was to determine the relationship between moderate hyperchloremia and acute kidney injury, as defined by the Acute Kidney Injury Network criteria. Secondary objectives included mortality and hospital length of stay. Results: A total of 407 patients were included in the unmatched cohort (332 nonhyperchloremia and 75 hyperchloremia) and 114 patients (57 in each group) were matched based upon propensity scores. In the matched cohort, hyperchloremia was associated with an increased risk of acute kidney injury (relative risk 1.91 [95% confidence interval 1.01-3.59]) and a longer hospital length of stay (16 vs 12 days; P = .03). Mortality was higher in the hyperchloremia group (19.3% vs 10.5%, P = .19), but this did not reach statistical significance. Conclusions: In this study, hyperchloremia after ischemic stroke was associated with increased rates of acute kidney injury and longer hospital length of stay. Further research is needed to determine which interventions may increase chloride levels in patients with acute ischemic stroke and the association between hyperchloremia and clinical outcomes.

scholarly journals Gustatory Function and the Uremic Toxin, Phosphate, Are Modulators of the Risk of Vascular Calcification among Patients with Chronic Kidney Disease: A Pilot Study

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 420
Author(s):  
Shih-I Chen ◽  
Chin-Ling Chiang ◽  
Chia-Ter Chao ◽  
Chih-Kang Chiang ◽  
Jenq-Wen Huang
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Estimated Glomerular Filtration Rate ◽  
Bitter Taste ◽  
Uremic Toxin ◽  
Gustatory Function ◽  
Increased Risk ◽  
The Relationship

Patients with chronic kidney disease (CKD) have an increased risk of vascular calcification (VC), including aortic arch calcification (AAC). Few investigated the influence of gustatory function on the probability of having VC. We examined whether gustatory function results modulated the probability of having VC in patients with CKD. We prospectively enrolled adults with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2), with their AAC rated semi-quantitatively and gustatory function assessed by objective and subjective approaches. Multiple logistic regression was used to analyze the relationship between gustatory function results and AAC. Those with AAC had significantly better objective gustatory function in aggregate scores (p = 0.039) and categories (p = 0.022) and less defective bitter taste (p = 0.045) and scores (p = 0.037) than those without. Multiple regression analyses showed that higher aggregate scores (odds ratio (OR) 1.288, p = 0.032), or better gustatory function, and higher bitter taste scores (OR 2.558, p = 0.019) were each associated with a higher probability of having AAC among CKD patients; such an association was modulated by serum phosphate levels. In conclusion, better gustatory function was independently correlated with having AAC among CKD patients. A follow-up of VC severity may be an underrecognized component of care for CKD patients with a preserved gustatory function.

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