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Vitamin D receptor and calcium sensing receptor polymorphisms and colorectal cancer survival in Newfoundland population
S56
Abstracts
Poster Session, Saturday 28 January 2017
of all patients, of which 64% within the first year of follow up and 84% in the first 2 years. A local regrowth was located endoluminal in 96% (n = 161) and in the loco-regional lymph nodes in 4% (n = 7). Distant metastasis occurred in 7% (n = 49), of which 65% in the first two years of follow-up. The overall 3 year-survival of all patients was 91% and for patients with a local regrowth this was 87%. Conclusions: This is the largest retrospective series of patients with rectal cancer in which surgery was omitted after induction therapy. These data illustrate differences in induction therapy as well as baseline or followup imaging strategies and provide some crude outcome data. Further prospective data collection on the Watch-and-Wait strategy for rectal cancer is needed to increase our knowledge on oncological safety of omitting surgery. This may contribute to international consensus on staging, treatment and surveillance guidelines in rectal cancer care. No conflict of interest. 451 POSTER Vitamin D receptor and calcium sensing receptor polymorphisms and colorectal cancer survival in Newfoundland population Y. Zhu1 , P. Wang1 , G. Zhai2 , B. Bapat3 , S. Sevtap2 . 1 Memorial University of Newfoundland, Division of Community Health and HumanitiesFaculty of Medicine, St. John’s, Canada; 2 Memorial University of Newfoundland, Division of Genetics − Faculty of Medicine, St. John’s, Canada; 3 University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Canada Background: Increased levels of vitamin D and calcium are associated with lower risks of colorectal cancer incidence and mortality. These anticarcinogenic effects may be mediated by the vitamin D receptor (VDR) and the calcium sensing receptor (CASR). We investigated associations of genetic variations in VDR and CASR with colorectal cancer survival and whether the associations vary by dietary vitamin D and calcium intakes. Material and Methods: A cohort of 532 colorectal cancer patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and recurrence until April 2010. Germline DNA samples were genotyped with the Illumina Omni-Quad 1 Million chip. Using a single nucleotide polymorphism (SNP) tagging approach, we selected a total of 24 tag SNPs in VDR and 17 SNPs in CASR for this analysis. Principal component analysis was utilized to examine the overall association of the genes with colorectal cancer. Kaplan–Meier curves and multivariate Cox models assessed single SNPs and relative haplotypes on VDR and CASR in relation to overall (OS) and disease-free survival (DFS). Results: We observed a gene-level association for CASR and colon cancer overall survival (P = 0.014). CASR SNP rs1354162 had a borderline significant association with colon cancer OS (unadjusted P = 0.0025; adjusted P = 0.077). Haplotype analysis within linkage blocks of CASR showed a global association between haplotypes based on four SNPs (rs1814740, rs35274320, rs1354162, and rs7637874) and the OS of colon cancer patients (P = 0.047). In particular, the AGAC haplotype was correlated with a marked reduced OS of colon cancer in comparison to the most common haplotype (HR, 0.29; 95% confidence interval (CI), 0.13–0.68). Although no gene-level associations were noted for VDR, the association between VDR SNP rs1544410 and colorectal cancer OS was of borderline significance after the adjustment of multiple comparison (hazard ratio (HR), 1.50; 95 CI, 1.17–1.94; unadjusted P = 0.0018; adjusted P = 0.060). Additionally, a significant interaction was seen between prediagnostic dietary calcium intake and a CASR GTGGGGC haplotype (rs10222633, rs10934578, rs3804592, rs17250717, rs1801725, rs1042636, and rs1802757), with decreased OS associated with this haplotype limited to only patients consuming dietary calcium below the median (HR, 1.87; 95% CI, 1.17–2.97; Pinteraction = 0.026). Conclusion: Our results suggest that polymorphic variations of CASR are associated with OS of colon cancer patients. The associations on survival among colorectal cancer patients may differ according to dietary calcium intake. No conflict of interest. 452 Tumor hypoxia in colorectal cancer evaluated by 18 F-fluoromisonidazol PET/CT
POSTER
M. Olarte1 , C. Luna2 , B. Rivera3 . 1 ABC Medical Center, nuclear medicine and molecular imaging, Mexico City, Mexico; 2 IMSS, Radiology, Mexico City, Mexico; 3 PET-CT UNAM, PET-CT, Mexico City, Mexico Background: Tumoral lesions invariably receive less oxygen than the normal tissues from which they grow. This phenomenon is called tumor hypoxia (THPX). THPX has a negative impact on patients with cancer due to mechanisms of chemo/radio resistance. The study of molecular
imaging 18 F-fluoromisonidazol (18 F-FMISO) PET/CT has been validated as a diagnostic test for THPX. Which is a non-invasive alternative to electrode Eppendorf. However, there is no evidence of the behavior of the hypoxia in colorectal cancer (CRC). Objective: To determine tumoral hypoxia in primary and metastatic lesions in colorectal cancer with a 18 F-FMISO PET/CT study. Method: A positive patients diagnosed with CRC in 18 F-FDG PET/CT scan was performed with 18 F-FMISO to assess the presence of THPX. Without receive cancer treatment between both scans. With acquisition 60 and 120 min post-injection of 18 F-FDG and 18 F-FMISO respectively. The maximum standardized uptake value (SUVmax) of each tumor drawing regions of interest was obtained. SUVmax >1.2 was the cutting range to define THPX. SPSS statistical software was used; with central tendency and dispersion measures for the descriptive component and hypothesis testing according to data distribution for the analytical component. P value (p < 005) were considered significant differences. With the intention of clearing the effect of the obtained sample size, the test was pondered with an expansion factor of 4 (minimum necessary to observe differences). Results: 28 patients were studied (16 F, 12 M, 38−77 years, mean 60.89). The most frequent location for the primary colorectal cancer tumor was descending colon (28.6%), sigmoid colon (25%), rectum (25%), and finally ascending colon (21.4%). 60 lesions were examined in total: 14 lymph nodes, 12 hepatic metastases, 12 lung metastases, 10 peritoneal lesions, 5 gastrointestinal tract lesions, 4 mesenteric lesions, 3 bone lesions, 3 in soft tissues, and 3 in other regions (retroperitoneal and adrenal lesions). With the objective of finding the correlation between the primary lesion and the metastasis locations, these were grouped into: bone and soft tissue, abdomen, and thorax. In this correlation test, no significant statistical differences were found. After pondering the sample with an expansion factor of 4, difference between soft tissue and bone were found. The relation between hypoxia and the examined lesions’ location did not show statistical significant values. After the sample was expanded by the same factor (4), statistical significant values were observed for the gastrointestinal tract, mesentery and peritoneum groups. Conclusions: The CRC metastases located in GIT, mesentery and peritoneum are more likely to manifest THPX, compared with those located in the liver, lung, soft tissue and bone. No conflict of interest. 453 POSTER Examining the direct and indirect effects of socioeconomic status (SES) on colorectal cancer risk using structural equation modeling J. Zhao1 , Y. Zhu1 , P. Wang1 . 1 Memorial University of Newfoundland, Division of Community Health and Humanities- Faculty of Medicine, St. John’s, Canada Background: Existing epidemiologic studies have not investigated how risk factors work together to increase the incidence of colorectal cancer (CRC) so the true effect of each factor could be under- or over estimated. This study explored how socio-economic status (SES) directly influenced the risk of developing CRC and its mediated effect on CRC risk through diet pattern while adjusting for the possible risk factors of alcohol intake, smoking, physical inactivity, and obesity. Material and Methods: This study used data collected from an existing population based case-control study of Newfoundland and Labrador, in which data pertaining to personal demographic characteristics, medical history, diet and other lifestyle factors were collected using selfadministered questionnaires. Measurement and structural modeling was used to test conceptual models. Exploratory factor analysis was used to identify dietary patterns measured by 39 food groups. Then, the direct and intermediate effects of risk factors were examined using structural equation modeling. Results: The results from multivariate regression analysis indicated that age (OR = 1.03), SES (OR = 0.89), processed meat intake (OR = 1.08), no CRC screening (OR = 2.67), smoking (OR = 1.44, 1.85 (ever, current)), and family history score of CRC (OR = 1.06), were significantly associated with the risk of CRC. SES has a direct effect (b = 0.05) on the risk of CRC. An indirect effect (b = 0.06) of SES on CRC risk also existed by influencing processed meat intake (b = 0.01), vegetables intake (b = 0.01), screening frequency (b = 0.02), and smoking (b = 0.02). Conclusions: This study suggested that the NL population has three major dietary patterns: (1) processed meats plus root vegetables; (2) vegetables; and (3) fruits). Structural equation modeling, a relatively new approach to epidemiology studies, provided unique information on the direct effect of socioeconomic status on the development of CRC but also SES’s indirect effect through a set of common CRC risk factors. No conflict of interest.
Abstracts
Poster Session, Saturday 28 January 2017
of all patients, of which 64% within the first year of follow up and 84% in the first 2 years. A local regrowth was located endoluminal in 96% (n = 161) and in the loco-regional lymph nodes in 4% (n = 7). Distant metastasis occurred in 7% (n = 49), of which 65% in the first two years of follow-up. The overall 3 year-survival of all patients was 91% and for patients with a local regrowth this was 87%. Conclusions: This is the largest retrospective series of patients with rectal cancer in which surgery was omitted after induction therapy. These data illustrate differences in induction therapy as well as baseline or followup imaging strategies and provide some crude outcome data. Further prospective data collection on the Watch-and-Wait strategy for rectal cancer is needed to increase our knowledge on oncological safety of omitting surgery. This may contribute to international consensus on staging, treatment and surveillance guidelines in rectal cancer care. No conflict of interest. 451 POSTER Vitamin D receptor and calcium sensing receptor polymorphisms and colorectal cancer survival in Newfoundland population Y. Zhu1 , P. Wang1 , G. Zhai2 , B. Bapat3 , S. Sevtap2 . 1 Memorial University of Newfoundland, Division of Community Health and HumanitiesFaculty of Medicine, St. John’s, Canada; 2 Memorial University of Newfoundland, Division of Genetics − Faculty of Medicine, St. John’s, Canada; 3 University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Canada Background: Increased levels of vitamin D and calcium are associated with lower risks of colorectal cancer incidence and mortality. These anticarcinogenic effects may be mediated by the vitamin D receptor (VDR) and the calcium sensing receptor (CASR). We investigated associations of genetic variations in VDR and CASR with colorectal cancer survival and whether the associations vary by dietary vitamin D and calcium intakes. Material and Methods: A cohort of 532 colorectal cancer patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and recurrence until April 2010. Germline DNA samples were genotyped with the Illumina Omni-Quad 1 Million chip. Using a single nucleotide polymorphism (SNP) tagging approach, we selected a total of 24 tag SNPs in VDR and 17 SNPs in CASR for this analysis. Principal component analysis was utilized to examine the overall association of the genes with colorectal cancer. Kaplan–Meier curves and multivariate Cox models assessed single SNPs and relative haplotypes on VDR and CASR in relation to overall (OS) and disease-free survival (DFS). Results: We observed a gene-level association for CASR and colon cancer overall survival (P = 0.014). CASR SNP rs1354162 had a borderline significant association with colon cancer OS (unadjusted P = 0.0025; adjusted P = 0.077). Haplotype analysis within linkage blocks of CASR showed a global association between haplotypes based on four SNPs (rs1814740, rs35274320, rs1354162, and rs7637874) and the OS of colon cancer patients (P = 0.047). In particular, the AGAC haplotype was correlated with a marked reduced OS of colon cancer in comparison to the most common haplotype (HR, 0.29; 95% confidence interval (CI), 0.13–0.68). Although no gene-level associations were noted for VDR, the association between VDR SNP rs1544410 and colorectal cancer OS was of borderline significance after the adjustment of multiple comparison (hazard ratio (HR), 1.50; 95 CI, 1.17–1.94; unadjusted P = 0.0018; adjusted P = 0.060). Additionally, a significant interaction was seen between prediagnostic dietary calcium intake and a CASR GTGGGGC haplotype (rs10222633, rs10934578, rs3804592, rs17250717, rs1801725, rs1042636, and rs1802757), with decreased OS associated with this haplotype limited to only patients consuming dietary calcium below the median (HR, 1.87; 95% CI, 1.17–2.97; Pinteraction = 0.026). Conclusion: Our results suggest that polymorphic variations of CASR are associated with OS of colon cancer patients. The associations on survival among colorectal cancer patients may differ according to dietary calcium intake. No conflict of interest. 452 Tumor hypoxia in colorectal cancer evaluated by 18 F-fluoromisonidazol PET/CT
POSTER
M. Olarte1 , C. Luna2 , B. Rivera3 . 1 ABC Medical Center, nuclear medicine and molecular imaging, Mexico City, Mexico; 2 IMSS, Radiology, Mexico City, Mexico; 3 PET-CT UNAM, PET-CT, Mexico City, Mexico Background: Tumoral lesions invariably receive less oxygen than the normal tissues from which they grow. This phenomenon is called tumor hypoxia (THPX). THPX has a negative impact on patients with cancer due to mechanisms of chemo/radio resistance. The study of molecular
imaging 18 F-fluoromisonidazol (18 F-FMISO) PET/CT has been validated as a diagnostic test for THPX. Which is a non-invasive alternative to electrode Eppendorf. However, there is no evidence of the behavior of the hypoxia in colorectal cancer (CRC). Objective: To determine tumoral hypoxia in primary and metastatic lesions in colorectal cancer with a 18 F-FMISO PET/CT study. Method: A positive patients diagnosed with CRC in 18 F-FDG PET/CT scan was performed with 18 F-FMISO to assess the presence of THPX. Without receive cancer treatment between both scans. With acquisition 60 and 120 min post-injection of 18 F-FDG and 18 F-FMISO respectively. The maximum standardized uptake value (SUVmax) of each tumor drawing regions of interest was obtained. SUVmax >1.2 was the cutting range to define THPX. SPSS statistical software was used; with central tendency and dispersion measures for the descriptive component and hypothesis testing according to data distribution for the analytical component. P value (p < 005) were considered significant differences. With the intention of clearing the effect of the obtained sample size, the test was pondered with an expansion factor of 4 (minimum necessary to observe differences). Results: 28 patients were studied (16 F, 12 M, 38−77 years, mean 60.89). The most frequent location for the primary colorectal cancer tumor was descending colon (28.6%), sigmoid colon (25%), rectum (25%), and finally ascending colon (21.4%). 60 lesions were examined in total: 14 lymph nodes, 12 hepatic metastases, 12 lung metastases, 10 peritoneal lesions, 5 gastrointestinal tract lesions, 4 mesenteric lesions, 3 bone lesions, 3 in soft tissues, and 3 in other regions (retroperitoneal and adrenal lesions). With the objective of finding the correlation between the primary lesion and the metastasis locations, these were grouped into: bone and soft tissue, abdomen, and thorax. In this correlation test, no significant statistical differences were found. After pondering the sample with an expansion factor of 4, difference between soft tissue and bone were found. The relation between hypoxia and the examined lesions’ location did not show statistical significant values. After the sample was expanded by the same factor (4), statistical significant values were observed for the gastrointestinal tract, mesentery and peritoneum groups. Conclusions: The CRC metastases located in GIT, mesentery and peritoneum are more likely to manifest THPX, compared with those located in the liver, lung, soft tissue and bone. No conflict of interest. 453 POSTER Examining the direct and indirect effects of socioeconomic status (SES) on colorectal cancer risk using structural equation modeling J. Zhao1 , Y. Zhu1 , P. Wang1 . 1 Memorial University of Newfoundland, Division of Community Health and Humanities- Faculty of Medicine, St. John’s, Canada Background: Existing epidemiologic studies have not investigated how risk factors work together to increase the incidence of colorectal cancer (CRC) so the true effect of each factor could be under- or over estimated. This study explored how socio-economic status (SES) directly influenced the risk of developing CRC and its mediated effect on CRC risk through diet pattern while adjusting for the possible risk factors of alcohol intake, smoking, physical inactivity, and obesity. Material and Methods: This study used data collected from an existing population based case-control study of Newfoundland and Labrador, in which data pertaining to personal demographic characteristics, medical history, diet and other lifestyle factors were collected using selfadministered questionnaires. Measurement and structural modeling was used to test conceptual models. Exploratory factor analysis was used to identify dietary patterns measured by 39 food groups. Then, the direct and intermediate effects of risk factors were examined using structural equation modeling. Results: The results from multivariate regression analysis indicated that age (OR = 1.03), SES (OR = 0.89), processed meat intake (OR = 1.08), no CRC screening (OR = 2.67), smoking (OR = 1.44, 1.85 (ever, current)), and family history score of CRC (OR = 1.06), were significantly associated with the risk of CRC. SES has a direct effect (b = 0.05) on the risk of CRC. An indirect effect (b = 0.06) of SES on CRC risk also existed by influencing processed meat intake (b = 0.01), vegetables intake (b = 0.01), screening frequency (b = 0.02), and smoking (b = 0.02). Conclusions: This study suggested that the NL population has three major dietary patterns: (1) processed meats plus root vegetables; (2) vegetables; and (3) fruits). Structural equation modeling, a relatively new approach to epidemiology studies, provided unique information on the direct effect of socioeconomic status on the development of CRC but also SES’s indirect effect through a set of common CRC risk factors. No conflict of interest.