Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival

Abstract Background MicroRNAs have important roles in tumorigenesis. There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS has been described in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA-miRNA binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC.Methods We conducted a case-control study of 507 CRC cases recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′ untranslated region (3′ UTR) with CRC susceptibility and survival. Deaths and causes of death among the CRC cases were identified using the Hangzhou Cancer Registration System and Death Surveillance System. Genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′ UTR of KRAS were selected using the Haploview and HaploReg software. Results Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared with adjacent normal mucosa. The Rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with CRC susceptibility (adjusted odds ratio 2.414, 95% CI: 1.385–4.206). Among non-smokers, the miR-143 rs41291957 GA genotype and miR-145 rs74693964 CT genotype were borderline significantly associated with an increased risk of rectal cancer. However, there was no interaction effect between selected SNPs and smoking status. Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). CRC cases carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio 4.328, 95% CI: 1.236–15.147). Conclusions Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for CRC susceptibility and survival.

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Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival

Bioscience Reports ◽

10.1042/bsr20204136 ◽

2021 ◽

Author(s):

Danyang Wang ◽

Qingmin Liu ◽

Yanjun Ren ◽

Yan Zhang ◽

Xin Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Genetic Polymorphisms ◽

Target Gene ◽

Cancer Susceptibility ◽

Gene Interaction ◽

Tertiary Hospital ◽

Cancer Tissue ◽

Nucleotide Polymorphisms ◽

Aberrant Expression ◽

Genomic Regions

Background There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA-miRNA binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC. Methods We conducted a case-control study of 507 patients with CRC recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′untranslated region (3′UTR) with susceptibility to CRC and patients’ survival. In addition, genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′UTR of KRAS were selected for analysis using the Haploview and HaploReg software. Results Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared to adjacent non-neoplastic large intestinal mucosa. The rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with susceptibility to CRC (adjusted odds ratio 2.414, 95% CI: 1.385–4.206). Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). Patients having CRC carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio 4.328, 95% CI: 1.236–15.147). Conclusions Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for susceptibility to CRC and patients’ survival.

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Epidemiology of Cancers in Kashmir, India: An Analysis of Hospital Data

Advances in Preventive Medicine ◽

10.1155/2016/1896761 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 17

Author(s):

Mariya A. Qurieshi ◽

S. M. Salim Khan ◽

Muneer A. Masoodi ◽

Uruj Qurieshi ◽

Quratul Ain ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Stomach Cancer ◽

Descriptive Analysis ◽

Geographic Region ◽

Cancer Registration ◽

Hospital Data ◽

Registration System ◽

Female Ratio ◽

Mortality And Morbidity

Cancer is a leading cause of mortality and morbidity in the world. The aim of the present study was to measure the pattern of different cancers in Kashmir, India, a cancer belt with peculiar cancer profile. A hospital based cancer registry was started by the Department of Community Medicine, Government Medical College, Srinagar, in January 2006, wherein information was collected from cancer patients who were diagnosed and treated in the hospital. Data has been analysed for a period extending from January 2006 to December 2012. Descriptive analysis has been done by using statistical software. A total of 1598 cancer patients were admitted during this period. Overall male to female ratio was 1.33 : 1. Stomach cancer was the most commonly reported cancer (25.2%), followed by colorectal cancer (16.4%) and lung cancer (13.2%) among males. For females, colorectal cancer (16.8%), breast cancer (16.1%), and stomach cancer (10.4%) were the most frequently reported cancers in order of frequency. Tobacco related cancers contributed to more than three-fourths of cancers among men and more than half of cancers for women. There is an urgent need to set up a population based cancer registration system to understand the profile of cancers specific to this geographic region.

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Inflammatory potential of diet and risk of colorectal cancer: a case–control study from Italy

British Journal Of Nutrition ◽

10.1017/s0007114515001828 ◽

2015 ◽

Vol 114 (1) ◽

pp. 152-158 ◽

Cited By ~ 52

Author(s):

Nitin Shivappa ◽

Antonella Zucchetto ◽

Maurizio Montella ◽

Diego Serraino ◽

Susan E. Steck ◽

...

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Case Control Study ◽

Continuous Variable ◽

Case Control ◽

Logistic Regression Models ◽

Inflammatory Index ◽

Colon And Rectal Cancer ◽

Increased Risk ◽

Control Study

Diet and inflammation have been suggested to be important risk factors for colorectal cancer (CRC). In the present study, we examined the association between the dietary inflammatory index (DII) and the risk of CRC in a multi-centre case–control study conducted between 1992 and 1996 in Italy. The study included 1225 incident colon cancer cases, 728 incident rectal cancer cases and 4154 controls hospitalised for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed using a validated seventy-eight-item FFQ that included assessment of alcohol intake. Logistic regression models were used to estimate the OR adjusted for age, sex, study centre, education, BMI, alcohol drinking, physical activity and family history of CRC. Energy intake was adjusted using the residual method. Subjects with higher DII scores (i.e. with a more pro-inflammatory diet) had a higher risk of CRC, with the DII being used both as a continuous variable (ORcontinuous 1·13, 95 % CI 1·09, 1·18) and as a categorical variable (ORquintile 5 v. 1 1·55, 95 % CI 1·29, 1·85; P for trend < 0·0001). Similar results were observed when the analyses were carried out separately for colon and rectal cancer cases. These results indicate that a pro-inflammatory diet is associated with an increased risk of CRC.

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Survival Analysis of 335 Patients With Colorectal Cancer Undergoing Combined Treatment

10.21203/rs.3.rs-146795/v1 ◽

2021 ◽

Author(s):

Daem Roshani ◽

Ghobad Moradi ◽

Mohammad Rasouli

Keyword(s):

Colorectal Cancer ◽

Survival Rate ◽

Cox Regression ◽

Survival Curve ◽

Combined Treatment ◽

Survival Rates ◽

Rank Test ◽

Cancer Registration ◽

Cancer Specific Survival ◽

Registration System

Abstract Introduction: If colorectal cancer (CRC) is diagnosed in the early stages, the patients will have higher survival rates. Although there might be some other factors which affect the survival rate, the kind of treatment available based on existing health and therapeutic facilities, is very important as well. The aim of this study was to explore the best type of treatment in colorectal cancer patients.Methods: The data of 335 patients with CRC in Kurdistan province were collected using population-based cancer registration system from first of March 2009 to 2014. Demographic and clinical- pathologic data of the patients were gathered through their medical and pathology records and going to the door of their houses. The cancer-specific survival rate were calculated using Kaplan-Meier survival curve, log-rank test, univariate and multivariate Cox regression. The data was analyzed using Stata 12 software. Results: One-year, three-year and five-year survival rates were %87, %57 and %33 respectively. The median of survival was 42.6 months. The five-year survival rate for those patients who had received both surgical and chemotherapy treatments was %55.8. There was less mortality rate among the patients who had received both surgical and chemotherapy treatments compared to those who had not received any treatment (HR=0.57, 95% CI 0.24-0.93).Conclusion: When CRC patients are treated using both surgical and chemotherapy treatments, they will have higher survival rate. Therefore, it is suggested to use both treatments for CRC patients.

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Risk and predictors of suicide in colorectal cancer patients: A SEER analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9596 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9596-9596

Author(s):

Haider Samawi ◽

Abdel Aziz Shaheen ◽

Patricia Tang ◽

Daniel Yick Chin Heng ◽

Winson Y. Cheung ◽

...

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Colon Cancer ◽

Cancer Patients ◽

Primary Tumor ◽

Univariate Analysis ◽

Male Gender ◽

White Race ◽

Colon And Rectal Cancer ◽

Increased Risk

9596 Background: Colorectal cancer (CRC) patients have a higher risk of suicide as compared with the general population. Due to differences in the sites/morbidity of recurrences as well as ostomy rates, we sought to evaluate the distribution and predictors of suicide among patients with colon and rectal cancer. Methods: A retrospective analysis was undertaken using the Surveillance, Epidemiology, and End Results (SEER) database from 1973-2009. Patients included were >18yrs and had confirmed adenocarcinoma of the colon or rectum. Results: Included in this analysis were 187,996 rectal cancer and 443,368 colon cancer patients. Colon cancer patients were older (median age 71 vs. 67 yrs, p <0.001) and included more females (51 vs. 43%, p <0.001) as compared to rectal cancer patients. Suicide rates were similar (611 [0.14%] vs. 337 [0.18%], p <0.001), as was the median time to suicide for colon vs. rectal cancer patients respectively (37 vs.32 months, p = 0.13). On univariate analysis, having rectal cancer was a predictor of suicide (HR 1.26; 95% CI: 1.10-1.43). However after adjustment for age, sex, race, marital, primary site surgery, stage and one primary, rectal cancer was not a predictor of suicide (HR 1.05; CI: 0.83- 1.33). In the combined CRC cohort, independent predictors of suicide included age >70 (HR 1.55; CI: 1.23-1.94), male gender (HR 7.56; CI: 5.34-10.70), being single (HR 1.56; CI: 1.14- 2.13), distant metastases at diagnosis (HR 1.58; CI: 1.13- 2.21), and white race (HR 3.21; CI: 1.75- 5.88). Also, lack of resection of primary tumor was associated with increased risk of suicide (HR 2.83; CI: 1.97- 4.05). Among colon cancer cohort, older age, male gender, and white race as well as lack of primary resection were independent predictors of suicide. Similarly, the aforementioned predictors as well as metastatic disease on presentation were the independent predictors of suicide in the rectal cohort. Conclusions: The suicide risk in CRC patients is low (< 0.2%) and no difference was found based on location of primary tumor. Gender, age, distant spread of disease, intact primary tumour and race are the main predictors of suicide among colorectal patients. Future studies and interventions are needed to target these high risk groups.

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Smoking-Related Risks of Colorectal Cancer by Anatomical Subsite and Sex

American Journal of Epidemiology ◽

10.1093/aje/kwaa005 ◽

2020 ◽

Vol 189 (6) ◽

pp. 543-553 ◽

Cited By ~ 2

Author(s):

Inger T Gram ◽

Song-Yi Park ◽

Lynne R Wilkens ◽

Christopher A Haiman ◽

Loïc Le Marchand

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Colon Cancer ◽

Cox Regression ◽

Left Colon ◽

Right Colon ◽

Right Colon Cancer ◽

Increased Risk ◽

The Right ◽

Incident Cases

Abstract The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45–75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993–1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts.

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Prognostic and predictive roles of microRNA-383 in colorectal cancer

Gastroenterology Insights ◽

10.4081/gi.2016.6641 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 1

Author(s):

Alavieh Fateh ◽

Mohammad Ali Hosseinpour Feizi ◽

Reza Safaralizadeh ◽

Mohammad Hossein Somi ◽

Reyhaneh Ravanbakhsh ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Marker ◽

Critical Role ◽

Predictive Biomarker ◽

Cancer Tissue ◽

Aberrant Expression ◽

Tissue Samples ◽

Noncancerous Tissue ◽

Expression Levels ◽

Roc Area

MicroRNAs (miRNAs) are impressive regulators of gene expression that have a critical role in the pathogenesis of colorectal cancer (CRC). With respect to the aberrant expression of miRNA-383 (miR-383) in some types of human malignancy, this prospective study characterized its contribution to CRC tumorigenesis. The real-time reverse transcriptionpolymerase chain reaction was used to examine miR-383 expression levels prospectively in 40 sample pairs of CRC tissues and adjacent noncancerous tissues (>2 cm from cancer tissue). No significant relationship was found between miR-383 expression levels and clinicopathological features. The ability of miR-383 to function as a tumor marker was also examined. Showing significant changes overall, miR-383 expression levels were significantly down regulated in the group of CRC samples compared with matched noncancerous tissue samples. A receiver-operating characteristic (ROC) curve also showed ROC area of 70% for miR-383 with 68 and 75% sensitivity and specificity, respectively. Therefore, miR-383 can be considered as a tumor marker in CRC and help as a potential predictive biomarker in the diagnosis of colorectal cancer.

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Nut and peanut butter intake and the risk of colorectal cancer and its anatomical and molecular subtypes: the Netherlands Cohort Study

Carcinogenesis ◽

10.1093/carcin/bgaa080 ◽

2020 ◽

Vol 41 (10) ◽

pp. 1368-1384

Author(s):

Lisette Nieuwenhuis ◽

Colinda C J M Simons ◽

Matty P Weijenberg ◽

Piet A van den Brandt

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Cohort Study ◽

Cancer Risk ◽

Peanut Butter ◽

Colorectal Tumors ◽

Increased Risk ◽

Nut Intake ◽

Serrated Neoplasia Pathway

Abstract Nut intake has been associated with reduced total cancer-related mortality, but evidence for colorectal cancer (CRC) risk is inconclusive. We investigated the associations between nut and peanut butter intake and anatomical CRC subtypes. To account for molecular heterogeneity, associations between nut and peanut butter intake and colorectal tumors harboring APC, KRAS or BRAF mutations, p53 overexpression or microsatellite instability were examined in secondary analyses. In the Netherlands Cohort Study (n = 120 852), lifestyle habits were measured with a questionnaire in 1986. After 20.3 years follow-up, 3567 CRC cases were included in case–cohort analyses. For the analyses of molecular CRC subtypes, 574 cases were included after 7.3 years follow-up. In categorical analyses, total nut intake was not significantly associated with CRC [HR (95% CI) 10+ g/day versus non-consumers = 0.94(0.78–1.15) in men; 0.96(0.75–1.22) in women]. In restricted cubic spline analyses, significant non-linear inverse associations with rectal cancer were observed for total nut, peanut and peanut butter intake in women, and borderline significant non-linear inverse associations for total nut and peanut intake in men. Regarding the molecular CRC subtypes, peanut butter intake was significantly associated with an increased risk of colorectal tumors that did not develop through the serrated neoplasia pathway in men [HR (95% CI) per 5 g/day increment = 1.22(1.07–1.38)]. Nut and peanut butter intake are non-linearly inversely associated with rectal cancer risk in women. In men, nut intake is borderline significantly non-linearly associated with a reduced rectal cancer risk. Peanut butter is associated with an increased risk of colorectal tumors that do not develop through the serrated neoplasia pathway in men.

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The Role of Smoking in the Development of Colorectal Cancer

Acta Medica Marisiensis ◽

10.1515/amma-2016-0046 ◽

2016 ◽

Vol 62 (4) ◽

pp. 400-402 ◽

Cited By ~ 1

Author(s):

Márton István Dénes ◽

Cristian Borz ◽

Árpád Török ◽

Tibor Kántor ◽

Valentin Nădășan ◽

...

Keyword(s):

Colorectal Cancer ◽

Rectal Cancer ◽

Heavy Smoker ◽

Public Health Issue ◽

Important Public Health ◽

Increased Risk ◽

Carcinogenic Substances ◽

Former Smokers ◽

Heavy Smokers

AbstractIntroduction. Smoking is an important public health issue nowadays. It causes a lot of diseases and represents also a source of carcinogenic substances. Recent studies showed an increased incidence of colorectal cancer in smokers. The aim of our study is to assess the association between smoking and colorectal cancer and to establish the prevalence of heavy smokers among the patients operated on for colorectal cancer.Methodology. We run a retrospective study of the charts belonging to the patients diagnosed with colorectal cancer and operated on in our department between 2004 and 2013. The patients were classified in smokers, former smokers and nonsmokers. The amount of tobacco was evaluated according to the number of smoked cigarettes per day, the smoking period, respectively the pack-years. The data were corroborated with the location of the tumor and analyzed using the online version of Graphpad.Results. From 982 patients diagnosed with colorectal cancer, we found 297 smokers (30.24%). Among these, 106 patients (35.69%) have smoked for over 30 years, at least 20 cigarettes per day, more than 30 pack-years. The number of heavy smokers was significantly greater (p=0.0001) in the group with rectal cancer compared to the group with colon cancer. The association of smoking with rectal cancer was also important (p=0.0015) among the former smokers.Conclusions. Smoking is related to higher incidence of colorectal cancer. Our data sustain the hypothesis of increased risk of developing rectal cancer in heavy smokers. We recommend the screening for colorectal cancer among the heavy smoker population.

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Survival Analysis Of 335 Patients With Colorectal Cancer Undergoing Combined Treatment

10.21203/rs.3.rs-255224/v1 ◽

2021 ◽

Author(s):

Ghobad Moradi ◽

Mohammad Aziz Rasouli ◽

Daem Roshani

Keyword(s):

Colorectal Cancer ◽

Survival Rate ◽

Cox Regression ◽

Survival Curve ◽

Combined Treatment ◽

Survival Rates ◽

Rank Test ◽

Cancer Registration ◽

Cancer Specific Survival ◽

Registration System

Abstract Purpose: If colorectal cancer (CRC) is diagnosed in the early stages, the patients will have higher survival rates. Although there might be some other factors which affect the survival rate, the kind of treatment available based on existing health and therapeutic facilities, is very important as well. The aim of this study was to explore the best type of treatment in colorectal cancer patients.Methods: The data of 335 patients with CRC in Kurdistan province were collected using population-based cancer registration system from first of March 2009 to 2014. Demographic and clinical- pathologic data of the patients were gathered through their medical and pathology records and going to the door of their houses. The cancer-specific survival rate were calculated using Kaplan-Meier survival curve, log-rank test, univariate and multivariate Cox regression. The data was analyzed using Stata 12 software. Results: One-year, three-year and five-year survival rates were %87, %57 and %33 respectively. The median of survival was 42.6 months. The five-year survival rate for those patients who had received both surgical and chemotherapy treatments was %55.8. There was less mortality rate among the patients who had received both surgical and chemotherapy treatments compared to those who had not received any treatment (HR=0.57, 95% CI 0.24-0.93).Conclusion: When CRC patients are treated using both surgical and chemotherapy treatments, they will have higher survival rate. Therefore, it is suggested to use both treatments for CRC patients.

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