Genetic risk factors for colorectal cancer in multiethnic Indonesians.
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ABSTRACT:
SUBMITTER: Yusuf I
PROVIDER: S-EPMC8113452 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIncreased exposure of colonic and rectal epithelial cells to the promitotic and antiapoptotic effects of insulin and insulin-like growth factors (IGF) is hypothesized to increase colorectal cancer risk.MethodsIn a case-control study nested within the Multiethnic Cohort, we attempted to replicate associations for five genetic variants associated with IGF system biomarkers, insulin, or glucose and to examine their association with the risk of colorectal cancer. In a subset of participants, the association between circulating biomarkers and colorectal cancer risk was examined. Unconditional logistic regression was used to calculate ORs and 95% confidence intervals (CI) for genetic variants (1,954 cases/2,587 controls) and serum biomarkers (258 cases/1,701 controls).ResultsAssociations with circulating biomarkers were replicated in the Multiethnic Cohort for IGF1 rs35767 and for IGFBP3 rs2854744, rs2854746, and rs3110697 (P < 0.05). Homozygous carriers of the glucokinase regulator (GCKR) rs780094 variant T-allele were at a decreased risk of colorectal cancer (OR, 0.77; 95% CI, 0.64-0.92). In risk factor-adjusted models, participants with the highest prediagnostic IGF-II levels were at an increased risk [OR (T1 vs. T3), 1.58; 95% CI, 1.09-2.28; P(trend) = 0.011] and participants with the highest prediagnostic IGF-binding protein (IGFBP)-3 levels were at a decreased risk of colorectal cancer (OR, 0.53; 95% CI, 0.34-0.83; P(trend) = 0.003).ConclusionThese data provide further support for a role of prediagnostic IGF and insulin levels in the etiology of colorectal cancer.ImpactFuture studies attempting to replicate the association between the GCKR rs780094 variant and the risk of colorectal cancer are warranted.
| S-EPMC4494075 | biostudies-literature
Project description:PurposeBoth genetic and lifestyle factors contribute to the risk of colorectal cancer, but each individual factor has a limited effect. Therefore, we investigated the association between colorectal cancer and the combined effects of genetic factors or/and lifestyle risk factors.Materials and methodsIn a case-control study of 632 colorectal cancer patients and 1,295 healthy controls, we quantified the genetic risk score for colorectal cancer using 13 polymorphisms. Furthermore, we determined a combined lifestyle risk score including obesity, physical activity, smoking, alcohol consumption, and dietary inflammatory index. The associations between colorectal cancer and risk score using these factors were examined using a logistic regression model.ResultsHigher genetic risk scores were associated with an increased risk of colorectal cancer (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.89 to 3.49 for the highest tertile vs. lowest tertile). Among the modifiable factors, previous body mass index, physical inactivity, heavy alcohol consumption, and a high inflammatory diet were associated with an increased risk of colorectal cancer. A higher lifestyle risk score was associated with an increased risk of colorectal cancer (OR, 5.82; 95% CI, 4.02 to 8.44 for the highest tertile vs. lowest tertile). This association was similar in each genetic risk category.ConclusionAdherence to a healthy lifestyle is associated with a substantially reduced risk of colorectal cancer regardless of individuals' genetic risk.
| S-EPMC6639208 | biostudies-literature
Project description:BackgroundCYP2C9 and VKORC1 are two major genetic factors associated with inter-individual variability in warfarin dose. Additionally, genes in the warfarin metabolism pathway have also been associated with dose variance. We analyzed Single Nucleotide Polymorphisms (SNPs) in these genes to identify genetic factors that might confer warfarin sensitivity in Indonesian patients.MethodsDirect sequencing method was used to identify SNPs in CYP2C9, VKORC1, CYP4F2, EPHX1, PROC and GGCX genes in warfarin-treated patients. Multiple linear regressions were performed to model the relationship warfarin daily dose requirement with genetic and non-genetic variables measured and used to develop a novel algorithm for warfarin dosing.ResultsFrom the 40 SNPs analyzed, CYP2C9 rs17847036 and VKORC1 rs9923231 showed significant association with warfarin sensitivity. In our study population, no significant correlation could be detected between CYP2C9*3, CYP2C9C-65 (rs9332127), CYP4F2 rs2108622, GGCX rs12714145, EPHX1 rs4653436 and PROC rs1799809 with warfarin sensitivity.ConclusionsVKORC1 rs9923231 AA and CYP2C9 rs17847036 GG genotypes were associated with low dosage requirements of most patients (2.05 ± 0.77 mg/day and 2.09 ± 0.70 mg/day, respectively). CYP2C9 and VKORC1 genetic variants as well as non-genetic factors such as age, body weight and body height account for 15.4% of variance in warfarin dose among our study population. Additional analysis of this combination could allow for personalized warfarin treatment in ethnic Indonesians.
| S-EPMC3133537 | biostudies-literature
Project description:Greater consumption of red and processed meat has been associated with an increased risk of colorectal cancer in several recent meta-analyses. Heterocyclic amines (HCAs) have been hypothesized to underlie this association. In this prospective analysis conducted within the Multiethnic Cohort Study, we examined whether greater consumption of total, red or processed meat was associated with the risk of colorectal cancer among 165,717 participants who completed a detailed food frequency questionnaire at baseline. In addition, we examined whether greater estimated intake of HCAs was associated with the risk of colorectal cancer among 131,763 participants who completed a follow-up questionnaire that included a meat-cooking module. A total of 3,404 and 1,757 invasive colorectal cancers were identified from baseline to the end of follow-up and from the date of administration of the meat-cooking module to the end of follow-up, respectively. Proportional hazard models were used to estimate basic and multivariable-adjusted relative risks (RRs) and 95% confidence intervals for colorectal cancer associated with dietary exposures. In multivariable models, no association with the risk of colorectal cancer was detected for density-adjusted total meat (RR(Q5 vs. Q1) = 0.93 [0.83-1.05]), red meat (RR = 1.02 [0.91-1.16]) or processed meat intake (RR = 1.06 [0.94-1.19]) or for total (RR = 0.90 [0.76-1.05]) or specific HCA intake whether comparing quintiles of dietary exposure or using continuous variables. Although our results do not support a role for meat or for HCAs from meat in the etiology of colorectal cancer, we cannot rule out the possibility of a modest effect.
| S-EPMC3553660 | biostudies-other
Project description:Colorectal cancer (CRC) is a disease preventable in up to 50% of the patients by lifestyle modifications. The preventive strategy for the decrease in the incidence and mortality of CRC is based on understanding the relations between the environmental and genetic factors. The most important identified risk factors for CRC are aging, personal and familial history of CRC or adenomas, hereditary colon cancer syndromes, dietary patterns, and inflammatory bowel disease. The purpose of this review is to update data referring to environmental and genetic documented factors and CRC risk. Using data from the Medline database, we analyzed reports on CRC risk published between 2000 and 2010. We realized a classification taking into consideration the relative risk (RR) reported for each analyzed factor (RR ranged between 1 and 6.87). The highest RR were represented by the patients with distal advanced cancer (RR = 6.7) and those with high dysplasia adenomas (RR = 6.87). In the future, evaluation and optimisation of screening options will stay at the base of new prevention strategies that will be implemented based on the influence of risk factors identified in each population.
| S-EPMC6880217 | biostudies-literature
Project description:BackgroundDiabetics have been found to have a greater risk of colorectal cancer than non-diabetics.MethodsWe examined whether this relationship differed by ethnic group, cancer site or tumour stage in a population-based prospective cohort, including 3549 incident colorectal cancer cases identified over a 13-year period (1993-2006) among 199 143 European American, African American, Native Hawaiian, Japanese American and Latino men and women in the Multiethnic Cohort.ResultsDiabetics overall had a significantly greater risk of colorectal cancer than did non-diabetics (relative risk (RR)=1.19, 95% confidence interval (CI)=1.09-1.29, P-value (P)<0.001). Positive associations were observed for colon cancer, cancers of both the right and left colon, and cancers diagnosed at a localised and regional/distant stage. The association with colorectal cancer risk was significantly modified by smoking status (P(Interaction)=0.0044), with the RR being higher in never smokers (RR=1.32, 95% CI=1.15-1.53, P<0.001) than past (RR=1.19, 95% CI=1.05-1.34, P=0.007) and current smokers (RR=0.90, 95% CI=0.70-1.15, P=0.40).ConclusionThese findings provide strong support for the hypothesis that diabetes is a risk factor for colorectal cancer.
| S-EPMC2905298 | biostudies-literature
Project description:Studies have provided evidence of an inverse association between atopic allergic conditions (AACs) and invasive colorectal cancer (CRC) incidence and mortality in predominantly white populations. We examined the association between AACs (asthma, hay fever, or allergy) and CRC among white, African-American, Native Hawaiian, Japanese-American, and Latino men and women in the Multiethnic Cohort Study within Hawaii and Los Angeles, California. The prospective analysis included 4,834 incident CRC cases and 1,363 CRC-related deaths ascertained between 1993 and 2010. We examined associations by ethnicity, location, stage, and potential effect modification by CRC risk factors. AACs were associated with a reduced risk of CRC incidence among both men and women (relative risk (RR) = 0.86, 95% confidence interval (CI): 0.80, 0.92). The reduction in risk was noted in all populations except Latinos and was significant in whites (RR = 0.85, 95% CI: 0.73, 0.98), African Americans (RR = 0.81, 95% CI: 0.70, 0.95), Native Hawaiians (RR = 0.72, 95% CI: 0.54, 0.96), and Japanese Americans (RR = 0.87, 95% CI: 0.78, 0.98). Individuals with AACs also had a 20% reduction in CRC-related mortality (P = 0.001). These findings provide evidence for the potential protective role of the reactive immune system in colorectal cancer.
| S-EPMC4445393 | biostudies-literature
Project description:Background & aimsThe combined effects of healthy lifestyle factors on colorectal cancer (CRC) risk are unclear. We aimed to develop a healthy lifestyle score, to investigate the joint effects of modifiable lifestyle factors on reduction of CRC risk and determine whether associations differ with genetic risk.MethodsWe collected data from a large population-based case-control study in Germany and used multiple logistic regression analyses to examine associations between the healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness) and CRC risk. We created a genetic risk score, based on 53 risk variants, to investigate the association of the healthy lifestyle score and risk of CRC, stratified by genetic risk.ResultsWe included 4092 patients with CRC and 3032 individuals without CRC (controls) in our analysis. In adjusted models, compared with participants with 0 or 1 healthy lifestyle factor, participants with 2 (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.67-1.06), 3 (OR 0.62; 95% CI 0.50-0.77), 4 (OR 0.53; 95% CI 0.42-0.66), or 5 (OR 0.33; 95% CI 0.26-0.43) healthy lifestyle factors had increasingly lower risks of CRC (P trend <.0001). We found no differences among subgroups stratified by genetic risk score, history of colonoscopy, or family history of CRC. Overall, 45% of CRC cases (95% CI 34%-53%) could be attributed to nonadherence to all 5 healthy lifestyle behaviors.ConclusionsIn a large population-based case-control study, we identified a combination of lifestyle factors that appears to reduce risk of CRC, regardless of the patient's genetic profile. These results reinforce the importance of primary prevention of CRC.
| S-EPMC6279591 | biostudies-literature
Project description:BackgroundDiabetes has been positively associated with the risk of colorectal cancer. This study investigated whether recently established risk variants for diabetes also have effects on colorectal cancer.Methods19 single nucleotide repeats (SNPs) associated with type 2 diabetes in genome-wide association studies were tested in a case-control study of 2011 colorectal cancer cases and 6049 controls nested in the Multiethnic Cohort study as part of the Population Architecture using Genomics and Epidemiology (PAGE) initiative. ORs and 95% CIs were estimated by unconditional logistic regression to evaluate the association between SNPs and colorectal cancer risk, adjusting for age, sex and race/ethnicity. Permutation testing was conducted to correct for multiple hypothesis testing.ResultsFour type 2 diabetes SNPs were associated with colorectal cancer risk: rs7578597 (THADA), rs864745 (JAZF1), rs5219 (KCNJ11) and rs7961581 (TSPAN8, LGR5). The strongest association was for the rs7578597 (THADA) Thr1187Ala missense polymorphism (P(trend)=0.004 adjusted for multiple testing), with the high risk allele for colorectal cancer being the low risk allele for diabetes. Similar patterns of associations were seen with further adjustment for diabetes status and body mass index. The association of diabetes status with colorectal cancer risk was somewhat weakened after adjustment for these SNPs.ConclusionThe findings suggest that diabetes risk variants also influence colorectal cancer susceptibility, possibly through mechanisms different from those for diabetes.
| S-EPMC4332884 | biostudies-literature
Project description:B vitamins, such as folate, vitamin B6, and vitamin B12, play an important role as coenzymes in one-carbon metabolism and may affect colorectal cancer risk. We aimed to comprehensively investigate the relationships of plasma folate, pyridoxal-5'-phosphate (PLP, the active form of vitamin B6), vitamin B12, methylmalonic acid, homocysteine, and cysteine with colorectal cancer risk, accounting for suspected modifiers (alcohol intake, MTHFR C677T genotype, and plasma C-reactive protein) and potential confounders. We conducted a case-control study nested within the Multiethnic Cohort study and analyzed prospectively collected blood samples from 224 incident colorectal cancer cases and 411 controls matched on age, sex, race/ethnicity, study site, date/time of blood draw, and hours of fasting. We found an inverse association between plasma PLP levels and colorectal cancer, with odds ratios (95% confidence intervals) for increasing quartiles of 1.00, 0.84 (0.51-1.40), 0.62 (0.37-1.03), and 0.49 (0.29-0.83), with P trend = 0.009. This association was not explained by an association with plasma folate, seemed to be stronger at low levels of alcohol intake and among individuals with the MTHFR 677TT genotype, and was independent of plasma C-reactive protein levels. An inverse association with plasma folate was also observed among individuals with a low level of alcohol intake. These data suggest an independent role for vitamin B6 in reducing colorectal cancer risk.
| S-EPMC2978659 | biostudies-literature