Presence Of Colorectal Cancer Research Articles

УЧЕТ ИНДЕКСА КОМОРБИДНОСТИ ПРИ ПРОВЕДЕНИИ ПРОТИВООПУХОЛЕВОЙ ЛЕКАРСТВЕННОЙ ТЕРАПИИ У ПАЦИЕНТОВ ПОЖИЛОГО И СТАРЧЕСКОГО ВОЗРАСТА С КОЛОРЕКТАЛЬНЫМ РАКОМ (ОБЗОР ЛИТЕРАТУРЫ)

The problem of treating elderly patients is one of the most pressing in modern clinical medicine. Colorectal cancer is one of the main causes of mortality from malignant neoplasms in Russia and other developed countries. At the same time, the incidence of tumors of the colon and rectum steadily increases with age. Before starting treatment for elderly patients, it is necessary to carefully weigh the potential risks and the possibility of achieving positive results of antitumor therapy. Objective: To summarize the literature on the use of a comprehensive geriatric assessment, including the Cancer and Aging Research Group (CARG) toxicity assessment, to predict the risk of adverse events during anticancer drug treatment in elderly patients diagnosed with colorectal cancer. Materials and methods: The search for scientific sources was carried out in PubMed / Medline / UpToDate using the following keywords: “malignant tumors”, “metastatic colorectal cancer”, “senile age”, “antitumor drug therapy”. The time horizon covered 2016–2023. Using a time filter, the most relevant and innovative research papers on the issues of chemotherapy treatment of elderly and senile patients were selected. Results: Most current evidence demonstrates the importance of performing a comprehensive geriatric assessment (CGA), Cancer and Aging Research Group (CARG) toxicity assessment in elderly and geriatric patients. Information obtained from geriatric assessment should be used to predict and manage treatment toxicity. And also for assessing and predicting overall survival. Activities based on CGA can reduce the toxicity of chemotherapy, improve the quality of life of patients, and increase compliance with medical recommendations. Undoubtedly, a comprehensive geriatric assessment (CGA) can help achieve the necessary balance between the potential effectiveness and adverse events of chemotherapy. The choice of treatment tactics for an elderly and senile cancer patient should be based on the patient’s functional status (PS), general somatic status according to the ECOG scale, and the risk of toxicity according to the CARG scale. In the presence of colorectal cancer, patients with good functional status who need antitumor systemic effects can be prescribed polychemotherapy with FOLFOX, XELOX, FOLFIRI doublets with the addition of targeted drugs: bevacizumab or cetuximab (depending on the results of gene profiling of the tumor). Patients who are not candidates for polychemotherapy in standard doses, who have a general somatic status on the ECOG scale of 1-2 and an average risk of developing toxicity of grade 3 on the CARG scale, can undergo PCT with FOLFOX, XELOX, FOLFIRI doublets with a reduction in the starting dose by 20%, or monochemotherapy with antimetabolites: capecitabine, 5-fluorouracil; topoisomerase I inhibitor irinotecan. Patients with poor functional status, general somatic status on the ECOG scale 3-4, and a high risk of developing toxicity on the CARG scale are not candidates for systemic combination chemotherapy. Particular attention should be paid to maintenance therapy in this subgroup of patients. However, if the decrease in PS level is directly related to malignancy and PS ≥2, the possibility of monochemotherapy by infusion of a combination of 5-fluorouracil and leucovorin FU/LV can be evaluated.

Assessing the Correlation between Helicobacter Pylori Infection and Increased Incidence of Colorectal Cancer, Gastric Atrophy, and Intestinal Metaplasia

Aim: Our retrospective study was designed to explore the potential link between Helicobacter pylori (H. pylori) infection and the occurrence of colorectal cancer (CRC), gastric atrophy, and intestinal metaplasia.
 Material and Methods: We assembled two groups of 150 patients each, categorized based on their endoscopic biopsy results for H. pylori - one group testing positive (study group), the other negative (control group). All subjects underwent upper and lower gastrointestinal endoscopies, and we assessed their endoscopic gastric biopsy results as well as any indications of colorectal malignancies.
 Results: Our investigation established a noteworthy association between the presence of H. pylori infection and the incidences of CRC, gastric atrophy, and intestinal metaplasia (p

Unplanned surgery after colorectal resection: laparoscopy at the index surgery is a protective factor against mortality.

The aim of this study wasto assess risk factors of mortality after unplanned surgery following colorectal resection. All the consecutive patients who underwent colorectal resection between 2011 and 2020 in a French national cohort were retrospectively included. Perioperative data of the index colorectal resection (indication, surgical approach, pathological analysis, postoperative morbidity), and characteristics of unplanned surgery (indication, time to complication, time to surgical redo) were assessed in order to identify predictive factors of mortality. Among 547 included patients, 54 patients died (10%; 32 men; mean age = 68 ± 18years, range 34-94years). Patients who died were significantly older (75 ± 11 vs 66 ± 12years, p = 0.002), frailer (ASA score 3-4 = 65 vs 25%, p = 0.0001), initially operated through open approach (78 vs 41%, p = 0.0001), and without any anastomosis (17 vs 5%, p = 0.003) than those alive. The presence of colorectal cancer, the time to postoperative complication and the time to unplanned surgery were not significantly associated to the postoperative mortality. After multivariate analysis, 5 independent predictive factors of mortality were identified: old age (OR 1.038; IC 95% 1.006-1.072; p = 0.02), ASA score = 3 (OR 5.9, CI95% 1.2-28.5, p = 0.03), ASA score = 4 (OR 9.6; IC95% 1.5-63; p = 0.02), open approach for the index surgery (OR 2.7; IC95% 1.3-5.7; p = 0.01), and delayed management (OR 2.6; IC95% 1.3-5.3; p = 0.009). After unplanned surgery following colorectal surgery, one out of 10 patients dies. The laparoscopic approach during the index surgery is associated with a good prognosis in the case of unplanned surgery.

Trends in the full blood count blood test and colorectal cancer detection: a longitudinal, case-control study of UK primary care patient data [version 2; peer review: 2 approved, 1 not approved

The full blood count (FBC) is a common blood test performed in general practice. It consists of many individual parameters that may change over time due to colorectal cancer. Such changes are likely missed in practice. We identified trends in these FBC parameters to facilitate early detection of colorectal cancer. We performed a retrospective, case-control, longitudinal analysis of UK primary care patient data. LOWESS smoothing and mixed effects models were derived to compare trends in each FBC parameter between patients diagnosed and not diagnosed over a prior 10-year period. There were 399,405 males (2.3%, n = 9,255 diagnosed) and 540,544 females (1.5%, n = 8,153 diagnosed) in the study. There was no difference between cases and controls in FBC trends between 10 and four years before diagnosis. Within four years of diagnosis, trends in many FBC levels statistically significantly differed between cases and controls, including red blood cell count, haemoglobin, white blood cell count, and platelets (interaction between time and colorectal cancer presence: p <0.05). FBC trends were similar between Duke's Stage A and D colorectal tumours, but started around one year earlier in Stage D diagnoses. Trends in FBC parameters are different between patients with and without colorectal cancer for up to four years prior to diagnosis. Such trends could help earlier identification.

Association between ERCC1 Gene Polymorphism (rs11615) and Colorectal Cancer Susceptibility: A Meta-Analysis of Medical Image Fusion and Safety Applications.

Colorectal cancer (CRC) is a malignant tumor of the colorectal mucosa epithelial tissue transformed. The fusion of data for medical imaging has become a central issue in such biomedical applications as image-guided surgery and radiotherapy. Currently, CRC has been one of the most threatening tumors affecting people's health worldwide. The excision repair cross-complementation group 1 (ERCC1) is a key enzyme for nucleotide excision repair (NER). Emerging epidemiological studies have indicated that the presence of colorectal cancer (CRC) may be relevant to the ERCC1 rs11615 genetic polymorphism. However, the results of ERCC1 rs11615 on CRC in these studies are controversial. We searched PubMed, Web of Science, Embase, CNKI, and CBM databases for the effects of ERCC1 rs11615 variant on CRC development. There was no meta-analysis focused on the diagnosis of colorectal cancer with ERCC1 rs11615 variant. We creatively carried out a meta-analysis of nine case-control studies and used Stata (version 12.0) software to integrate the pooled odds ratios (ORs) corresponding to a 95% confidence interval (CI) of overall and subgroup analysis. Our results suggest that a significant correlation was observed between rs11615 and the susceptibility of CRC OR 95% CI = 1.13 (1.04-1.23) under an allele genetic model and OR 95% CI = 1.14 (1.01-1.30) under a dominant genetic model for overall CRC. Significant statistical difference was also noted in Asians rather than Caucasians based on the ethnicity subgroups. These results suggested that there is a certain association between rs11615 and the susceptibility of colorectal cancer in the Asian populations.

Trends in the full blood count blood test and colorectal cancer detection: a longitudinal, case-control study of UK primary care patient data

Background: The full blood count (FBC) is a common blood test performed in general practice. It consists of many individual parameters that may change over time due to colorectal cancer. Such changes are likely missed in practice. We identified trends in these FBC parameters to facilitate early detection of colorectal cancer. Methods: We performed a retrospective, case-control, longitudinal analysis of UK primary care patient data. LOWESS smoothing and mixed effects models were derived to compare trends in each FBC parameter between patients diagnosed and not diagnosed over a prior 10-year period. Results: There were 399,405 males (2.3%, n = 9,255 diagnosed) and 540,544 females (1.5%, n = 8,153 diagnosed) in the study. There was no difference between cases and controls in FBC trends between 10 and four years before diagnosis. Within four years of diagnosis, trends in many FBC levels statistically significantly differed between cases and controls, including red blood cell count, haemoglobin, white blood cell count, and platelets (interaction between time and colorectal cancer presence: p &lt;0.05). FBC trends were similar between Duke’s Stage A and D colorectal tumours, but started around one year earlier in Stage D diagnoses. Conclusions: Trends in FBC parameters are different between patients with and without colorectal cancer for up to four years prior to diagnosis. Such trends could help earlier identification.

The analysis of impact of medical social and economic factors on regional coloproctological morbidity of adult population

Actually, there is constant increase of number of patients with coloproctological diseases, including corresponding malignant neoplasms. At that, issues of improving organization of specialized care of patients of this kind still remain unresolved in many positions. The retrospective analysis of regional coloproctological morbidity of adult population was carried out as exemplified by the Perm Kray. To forecast onset of colorectal cancer multiple logistic regression analysis was applied. To assess relationship of particular factors and morbidity, the Spearman rank correlation method was implemented. The ROC-analysis was applied using MedCalc software. The study established strong relationship between the presence of colorectal cancer and colon polyps (87.2%, Somers' D = 0.868). According to ROC analysis data, colon polyps are risk factor of development of colorectal cancer in 93.4% of cases. The pronounced relationship is demonstrated for presence of colon polyps and colorectal cancer detectability (OR 225.85, CI 61.5 - 829.15, p <0.0001). The results of analysis of regional coloproctological morbidity of adult population in 45 municipalities of the Perm Kray testify significant variability of territorial features. The study revealed that level of coloproctological morbidity in municipalities depends on such indices as provision of physicians and hospital beds and average salary. The study results testify necessity to consider territorial characteristics of Perm Kray in planning complex coloproctological care of population. The identified interrelationships of population morbidity, activities and resource support are to be taken into account in planning organizational measures to modernize treatment and preventive care of coloproctological patients, including early diagnosis of coloproctological cancer in combination with other measures to reduce overall level of coloproctological morbidity on territory of Perm Kray and to improve quality of life of patients.

Blood Copper Levels and the Occurrence of Colorectal Cancer in Poland.

There is a need for sensitive and specific biomarkers for the early detection of colorectal cancer. In this retrospective study, we assessed whether a high blood copper level was associated with the presence of colorectal cancer. The blood copper level was measured among 187 colorectal cancer patients and 187 matched controls. Cases and controls were matched for sex, smoking status (yes/no) and year of birth. Among the cases, the mean blood copper level was 1031 µg/L (range 657 µg/L to 2043 µg/L) and among the controls, the mean blood copper level was 864 µg/L (range 589 µg/L to 1433 µg/L). The odds ratio for colorectal cancer for those in the highest quartile of copper level (versus the lowest) was 12.7 (95% CI: 4.98–32.3; p < 0.001). Of the patients with stage I–II colon cancer, 62% had a copper level in the highest quartile. A blood copper level in excess of 930 µg/L is associated with an increase in the prevalence of colorectal cancer in the Polish population and its potential use in early detection programs should be considered.

Motives for non-adherence to colonoscopy advice after a positive colorectal cancer screening test result: a qualitative study

Setting Participants with a positive faecal immunochemical test (FIT) in screening programs for colorectal cancer (CRC) have a high risk for colorectal cancer and advanced adenomas. They are therefore recommended follow-up by colonoscopy. However, more than ten percent of positively screened persons do not adhere to this advice. Objective To investigate FIT-positive individuals’ motives for non-adherence to colonoscopy advice in the Dutch CRC screening program. Subjects Non-adherent FIT-positive participants of the Dutch CRC screening program. Design We conducted semi structured in-depth interviews with 17 persons who did not undergo colonoscopy within 6 months after a positive FIT. Interviews were undertaken face-to-face and data were analysed thematically with open coding and constant comparison. Results All participants had multifactorial motives for non-adherence. A preference for more personalised care was described with the following themes: aversion against the design of the screening program, expectations of personalised care, emotions associated with experiences of impersonal care and a desire for counselling where options other than colonoscopy could be discussed. Furthermore, intrinsic motives were: having a perception of low risk for CRC (described by all participants), aversion and fear of colonoscopy, distrust, reluctant attitude to the treatment of cancer and cancer fatalism. Extrinsic motives were: having other health issues or priorities, practical barriers, advice from a general practitioner (GP) and financial reasons. Conclusion Personalised screening counselling might have helped to improve the interviewees’ experiences with the screening program as well as their knowledge on CRC and CRC screening. Future studies should explore whether personalised screening counselling also has potential to increase adherence rates. Key points Participants with a positive FIT in two-step colorectal cancer (CRC) screening programs are at high risk for colorectal cancer and advanced adenomas. Non-adherence after an unfavourable screening result happens in all CRC programs worldwide with the consequence that many of the participants do not undergo colonoscopy for the definitive assessment of the presence of colorectal cancer. Little qualitative research has been done to study the reasons why individuals participate in the first step of the screening but not in the second step. We found a preference for more personalised care, which was not reported in previous literature on this subject. Furthermore, intrinsic factors, such as a low risk perception and distrust, and extrinsic factors, such as the presence of other health issues and GP advice, may also play a role in non-adherence. A person-centred approach in the form of a screening counselling session may be beneficial for this group of CRC screening participants.

Upstaging nodal status in colorectal cancer using ex vivo fluorescence sentinel lymph node mapping: preliminary results

Background Sentinel lymph node (SLN) mapping using near-infrared fluorescence (NIRF) imaging is a recent technique to improve nodal staging in several tumors. The presence of colorectal cancer (CRC) micro-metastases has recently been defined as N1 disease and no longer as N1mi, determining the need for adjuvant chemotherapy. In CRC, the reported rate of SLN micro-metastases detected by ultrastaging techniques is as high as 30%. The aim of this prospective study is to report the preliminary results of the sensitivity analysis of NIRF imaging for ex vivo SLN mapping and the research of micro-metastases in CRC, in patients with node-negative disease (NND). Material and methods On the specimen of 22 CRC patients, 1 mL of ICG (5 mg/mL) was injected submucosally around the tumor to identify SLNs. NND SLNs were further investigated with ultrastaging techniques. Results Three-hundred and sixty-three lymph nodes were retrieved (59 SLNs; mean per case: 2.7). The detection, sensitivity and false-negative rate were 100%, 100% and 0% respectively. Ultrastaging investigations showed no micro-metastases in the NND SLNs. Conclusions The ex vivo SLN fluorescence-based detection in CRC was confirmed to be easy to perform and reliable. In this preliminary results report of an ongoing study, the SLN assay was congruent with the nodal status, as confirmed by histological investigations.

Ten-year impact of pancreaticoduodenectomy on bowel function and quality of life of patients with ileal pouch-anal anastomosis for familial adenomatous polyposis

BackgroundPatients with familial adenomatous polyposis (FAP) carry a risk of duodenal adenocarcinoma. These patients, who already have an ileal pouch-anal anastomosis (IPAA), sometimes require pancreaticoduodenectomy (PD). This work aims to evaluate the long-term consequences of the combination of PD + IPAA. MethodsAll patients with IPAA due to FAP who underwent PD from 1991 to 2017 were included (PD + IPAA group). Patients were matched 1:1 according to age, sex, ASA score and presence of colorectal cancer. Fecal continence and quality of life (QoL) were assessed using the Wexner score and the EORTC-QLQ-C30 questionnaire. ResultsThirty-two PD + IPAA patients were matched with thirty-two IPAA-only patients. In each group, the response rate to the questionnaire was 78% (25/32). No differences were noted between PD + IPAA and IPAA-only groups in terms of daytime fecal frequency (6.0 vs 6.0; p = 0.362), Wexner score (3/20 vs 4/20; p = 0.984) and global QoL score (83.3/100 vs 83.3/100; p = 0.401). In the PD + IPAA group, 26% of patients developed diabetes a median period of 10.0 years after PD. The global QoL for these patients was significantly altered (p = 0.011), while daytime fecal frequency was unaffected (p = 0.092) as fecal continence (p = 0.475). ConclusionIn FAP patients with IPAA, PD does not affect bowel function or QoL.

Is visceral obesity associated with colorectal cancer? The first volumetric study using all CT slices.

We aimed to examine the possible relationship between abdominal adiposity parameters and the presence of colorectal cancer (CRC) and between these adiposity parameters and various histopathologic findings of the tumor. A total of 60 control subjects and 111 CRC patients, 63 with early-stage and 48 with advanced-stage disease, were enrolled. Medical data and abdominopelvic computed tomography (CT) examinations of each study group were retrospectively reviewed. Abdominal adiposity parameters, including visceral adipose tissue (VAT) volume, subcutaneous adipose tissue (SAT) volume, and total adipose tissue (TAT) volume, were calculated on all slices of the CT examinations with specialized software, and results for each study group were compared. Adiposity parameters were also compared with tumor histopathologic findings. We found lower VAT and higher SAT volumes in advanced-stage CRC patients, compared with the early-stage group. However, this relationship was not statistically significant (P = 0.721 for VAT and P = 0.432 for SAT volumes). We detected significantly lower VAT and SAT volumes in the early-stage CRC group compared with the control group (P = 0.014 for both). There was no significant relationship between TAT volumes and the study groups (P = 0.06). No statistically significant relationship was detected between adipose tissue parameters and histopathologic features of the CRC group (P > 0.05). We found statistically significant lower VAT and SAT volumes in patients with early-stage CRC compared with the control group. Volumetric adipose tissue measurements may be more accurate than area measurements and can easily be performed on abdominopelvic CT examination, which is the routine imaging modality for CRC patients.

Colorectal cancer and Cryptosporidium spp. infection.

Transient or constant impaired immunity is often associated with neoplastic disease or oncological treatment. Among the most common pathogens found in patients with HIV or patients undergoing chemotherapy are protozoans of the Cryptosporidium genus, which cause diarrhea in humans and animals. The present study determined the frequency of Cryptosporidium spp. infections in patients with colorectal cancer (N = 108; 42 women; 66 men; median age, 65 years), before beginning oncological treatment, compared to a control group (N = 125; 56 women, 69 men; median age, 63 years) without colorectal cancer or a history of oncological disease. We also assessed whether Cryptosporidium spp. infections were associated with age, gender, cancer stage (based on Astler-Coller or TNM classification), histological grade, or cancer location. Patients were treated at the Pomeranian Medical University, in 2009–2014. The presence of Cryptosporidium spp. antigen was determined in stool samples, analyzed with a commercial immunoenzymatic test. Cryptosporidium spp. infections occurred significantly more often (p = 0.015) in patients (13%) compared to controls (4%). The patient group showed no significant relationship between Cryptosporidium spp. infection and sex, age, tumor location, cancer grade, or stage. A multivariate logistic regression analysis adjusted for age and sex that included all subjects (patient + control groups, n = 233) showed that the odds of a Cryptosporidium spp. infection were more than three-fold higher in patients than in controls, and more than six-fold higher among men than among women. Conclusions: 1) Cryptosporidium spp. infections occurred significantly more frequently in patients with colorectal cancer (before oncological treatment) compared to controls, independent of age and sex. 2) Cryptosporidium spp. infections were not associated with the colorectal cancer stage, grade, or location or with patient age. 3) Male gender was significantly related to the frequency of Cryptosporidium spp. infections, independent of age and the presence of colorectal cancer.

Association between natural killer cell activity and the risk of colorectal neoplasia.

Low activity of natural killer (NK) cells is known to be associated with higher risk of cancer, especially with poor prognosis and the presence of colorectal cancer (CRC). We investigated whether NK cells activity differs between subjects with and without colorectal neoplasia (CRN). A cross-sectional study was performed on 1818 asymptomatic examinees aged ≥30years who underwent NK cell activity test (which quantitates the amount of interferon-γ secreted into the plasma by NK cells) and a colonoscopy as part of a health checkup. The mean age of the study population was 41.4years. The proportion of overall CRN and advanced CRN was 13.5% (n=246) and 0.7% (n=13), respectively. Only one subject was diagnosed with CRC. The median level of NK cell activity was lower in subjects with CRN than in those without CRN (1205 vs 1515pg/mL, P=0.009). It was also lower in subjects with non-advanced CRN than in those without CRN (1221 vs 1515pg/mL; P=0.036). Moreover, it was lower in subjects with advanced CRN than in those with non-advanced CRN (480 vs 1221pg/mL; P=0.028). Subjects with low levels of NK cell activity (<250pg/mL) had a higher prevalence of overall CRN (19.0% vs 12.9%, P=0.024) and advanced CRN (3.4% vs 0.4%, P=0.001) than those who demonstrated higher level (≥250pg/mL). Natural killer cell activity seemed to decrease along with CRC progression toward the later stages in the adenoma-carcinoma sequence. Its activity may be depressed in relation to progression of neoplasia, even at precancerous stage.

Simple sugars in fruit and the presence of colorectal cancers and polyps

Simple sugars in fruit and the presence of colorectal cancers and polyps

Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study

Colorectal cancer is a leading cause of morbidity and mortality worldwide in both men and women. The gut microbiome is increasingly recognized as having an important role in human health and disease. Fusobacterium has been identified in former studies as a leading gut bacterium associated with colorectal cancer, but it is still not clear if it plays an oncogenic role. In the current study, fecal samples were collected prior to bowel preparation from participants of screening colonoscopy in the German BliTz study. Using 16S rRNA gene analysis, we examined the presence and relative abundance of Fusobacterium in fecal samples from 500 participants, including 46, 113, 110 and 231 individuals with colorectal cancer, advanced adenomas, non-advanced adenomas and without any neoplasms, respectively. We found that the abundance of Fusobacterium in feces was strongly associated with the presence of colorectal cancer (P-value < 0.0001). This was confirmed by PCR at the species level for Fusobacterium nucleatum. However, no association was seen with the presence of advanced adenomas (P-value = 0.80) or non-advanced adenomas (P-value = 0.80), nor were there any associations observed with dietary or lifestyle habits. Although a causal role cannot be ruled out, our observations, based on fecal microbiome, support the hypothesis that Fusobacterium is a passenger that multiplies in the more favorable conditions caused by the malignant tumor rather than a causal factor in colorectal cancer development.

Abstract P2-07-13: TP53 gene polymorphisms (c.[215G&amp;gt;C]) in breast cancer patients and predisposition to family cancers- Single center experience

Abstract Introduction: Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers, and germline mutations are the underlying cause of Li-Fraumeni syndrome, which predisposes to a wide spectrum of early-onset cancers. The aim of this study was to evaluate the association between TP53 gene polymorphisms (c.[215G&amp;gt;C]) and predisposition to family cancers. Methods: We reviewed the medical records of 89 (21% TP53 gene homozygotes and 79% heterozygotes) breast cancer patients who were diagnosed and treated in COI in Gliwice. The history of family cancers was colected from medical history. Mutation profile was assessed by RFLP-PCR technique. We evaluatedthe presence ofpolymorphism TP53 (c.[215G&amp;gt;C]). Statistical analysis was carried out using STATISTICA 7 software. Results: Cancers in family history were detected in 72% of pts with TP53 polymorphisms and they were observed insignificantly more often in heterozygotes than in homozygotes (76% vs. 58%, p=0.153). The most frequently reported cancers were: breast cancer (33%), lymphoma (17%), colorectal cancer (9%), OUN cancer (8%), gastric cancer (8%), pancreatic cancer (7%), ovarian cancer (6%) and renal cancer (3%). In analyzed group, renal cancers in family were detected more frequently in TP53 homozygotes than in heterozygotes (16% vs. 0, p=0.008). Similarly, there was also observed tendency to the presence of colorectal cancer in TP53 homozygotes (11% vs. 0, p=0.193). Ovarian cancers and cholangiocarcinomas in family were also observed insignificantly more often in homozygotes than in heterozygotes (7% vs. 0, p=0.580) and (5% vs. 1%, p=0.383). There was no association between number of cancers in family and TP53 polymorphisms (47% vs. 43%, p=0.797). Conclusion: TP53 polymorphism (c.[215G&amp;gt;C]) predisposed to development renal and colorectal cancers (TP53 homozygotes) and ovarian cancer or cholangiocarcinoma (TP53 heterozygotes) in family. Citation Format: Huszno J, Grzybowska E, Nycz Bochenek M, Pamula Pilat J, Tecza K, Nowara E. TP53 gene polymorphisms (c.[215G&amp;gt;C]) in breast cancer patients and predisposition to family cancers- Single center experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-13.

Type and frequency of MUTYH variants in Italian patients with suspected MAP: a retrospective multicenter study.

To determine prevalence, spectrum and genotype-phenotype correlations of MUTYH variants in Italian patients with suspected MAP (MUTYH-associated polyposis), a retrospective analysis was conducted to identify patients who had undergone MUTYH genetic testing from September 2002 to February 2014. Results of genetic testing and patient clinical characteristics were collected (gender, number of polyps, age at polyp diagnosis, presence of colorectal cancer (CRC) and/or other cancers, family data). The presence of large rearrangements of the MUTYH gene was evaluated by Multiplex Ligation-dependent Probe Amplification analysis. In all, 299 patients with colorectal neoplasia were evaluated: 61.2% were males, the median age at polyps or cancer diagnosis was 50 years (16-80 years), 65.2% had <100 polyps and 51.8% had CRC. A total of 36 different MUTYH variants were identified: 13 (36.1%) were classified as pathogenetic, whereas 23 (63.9%) were variants of unknown significance (VUS). Two pathogenetic variants were observed in 78 patients (26.1%). A large homozygous deletion of exon 15 was found in one patient (<1.0%). MAP patients were younger than those with negative MUTYH testing at polyps diagnosis (P<0.0001) and at first cancer diagnosis (P=0.007). MAP patients carrying the p.Glu480del variant presented with a younger age at polyp diagnosis as compared to patients carrying p.Gly396Asp and p.Tyr179Cys variants. A high heterogeneity of MUTYH variants and a high rate of VUS were identified in a cohort of Italian patients with suspected MAP. Genotype-phenotype analysis suggests that the p.Glu480del variant is associated with a severe phenotype.

Linking cancer-induced Nlrp3 inflammasome activation to efficient NK cell-mediated immunosurveillance

ABSTRACTWe have recently demonstrated that the Nlrp3 inflammasome can detect the presence of colorectal cancer (CRC) metastatic growth in the liver and limit its growth. Inflammasome signaling primed natural killer (NK) cells through Interleukin (IL)-18 and activated their ability to trigger FasL-induced apoptosis of the tumor.

Differential susceptibility to colorectal cancer due to naturally occurring gut microbiota.

Recent studies investigating the human microbiome have identified particular bacterial species that correlate with the presence of colorectal cancer. To evaluate the role of qualitatively different but naturally occurring gut microbiota and the relationship with colorectal cancer development, genetically identical embryos from the Polyposis in Rat Colon (Pirc) rat model of colorectal cancer were transferred into recipients of three different genetic backgrounds (F344/NHsd, LEW/SsNHsd, and Crl:SD). Tumor development in the pups was tracked longitudinally via colonoscopy, and end-stage tumor burden was determined. To confirm vertical transmission and identify associations between the gut microbiota and disease phenotype, the fecal microbiota was characterized in recipient dams 24 hours pre-partum, and in Pirc rat offspring prior to and during disease progression. Our data show that the gut microbiota varies between rat strains, with LEW/SsNHsd having a greater relative abundance of the bacteria Prevotella copri. The mature gut microbiota of pups resembled the profile of their dams, indicating that the dam is the primary determinant of the developing microbiota. Both male and female F344-Pirc rats harboring the Lewis microbiota had decreased tumor burden relative to genetically identical rats harboring F344 or SD microbiota. Significant negative correlations were detected between tumor burden and the relative abundance of specific taxa from samples taken at weaning and shortly thereafter, prior to observable adenoma development. Notably, this naturally occurring variation in the gut microbiota is associated with a significant difference in severity of colorectal cancer, and the abundance of certain taxa is associated with decreased tumor burden.