Elevated Risk Of Colorectal Cancer Research Articles

Factors Associated With Colorectal Cancer Screening Among First-Degree Relatives of Patients With Colorectal Cancer in China.

First-degree relatives of patients with colorectal cancer have an elevated risk of colorectal cancer. However, the behavior and factors potential influencing first-degree relatives regarding colorectal cancer screening in China remain unknown. The aim of this study was to explore the screening behavior and related factors of first-degree relatives of colorectal cancer patients. A cross-sectional design was applied, and 201 first-degree relatives participated from August 2018 to July 2019. Data were collected about demographic information, the "Colorectal Cancer Perceptions Scale," and screening behavior of first-degree relatives. Factors associated with screening behavior were identified using logistic regression analysis. Only 18.9% of first-degree relatives had participated in colonoscopy screening. Two Health Belief Model factors were the influencing factors of their participation in colorectal cancer screening. Higher possibility of colorectal cancer screening of first-degree relatives was associated with higher perceived susceptibility (odds ratio, 1.224; 95% confidence interval, 1.075-1.395) and lower perception of barriers (odds ratio, 0.880; 95% confidence interval, 0.820-0.944) of first-degree relatives. Participation in colorectal cancer screening by first-degree relatives requires improvement; perceived susceptibility and perception of barriers were the most important predictors. Health professionals can enhance awareness of colorectal cancer susceptibility and address barriers to colorectal cancer screening among first-degree relatives at both individual and social levels.

The Analysis of NADPH Quinone Reductase 1 (NQO1) Polymorphism in Polish Patients with Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in Poland. Based on the findings of clinical trials, it is safe to conclude that genetic predisposition and environmental factors are the main factors responsible for the formation of colorectal cancer.The NQO1 gene plays an important role in reducing endogenous and exogenous quinones as well as quinone compounds to hydroquinones. It is an enzyme which is a part of the body’s antioxidant defense system. The aim of the study was to evaluate the correlation between the 609C > T polymorphism of the NQO1 gene and colorectal cancer risk in the Polish population. A total of 512 people were recruited for the study, including 279 patients with colorectal cancer, diagnosed at the University Hospital, Pomeranian Medical University in Szczecin. Genomic DNA was isolated from peripheral blood and the analyzed polymorphism was determined by PCR-RFLP. In the present study, we analyzed the clinical valuesand frequency of NQO1 609C > T polymorphism in patients diagnosed with colorectal cancer and controls. In case of the carriers of the TT genotype of the NQO1 polymorphism, an elevated risk for colorectal cancer was observed (OR = 2.96; 95% CI: 1.02–10.40). The analysis of the clinical parameters concerning the location and characteristics of the tumor stage revealed a statistically significant increase in the risk for colorectal cancer in the carriers of the TT genotype of the NQO1 polymorphism.

Colorectal neoplasms in melanosis coli: a survey in Japan and a worldwide meta-analysis.

The association between melanosis coli (MC) and colorectal neoplasms remains unclear. Thus, we primarily aimed to clarify the epidemiology of MC in the Japanese population, identify the relationship between the use of anthranoids and MC, and determine the prevalence of detected intestinal lesions in patients with MC. We subsequently conducted a meta-analysis of published data, including our results, to summarize the influence of MC on the prevalence of colonic neoplasms. We conducted a retrospective survey in Japan to investigate the effects of MC on intestinal disorders. The prevalence of colorectal neoplasms and ileal ulcers was evaluated by colonoscopy, and the clinical characteristics of the participants were investigated using an electronic database. Odds ratios for colorectal neoplasms were calculated. We also performed a meta-analysis using Review Manager to reveal the comprehensive relationship between MC and colorectal neoplasms. We enrolled 690 Japanese participants in the primary study. The prevalence of regular anthranoid use was significantly higher in the MC group than in the control group (50.9% vs. 6.5%, p < 0.01). Hyperplastic/inflammatory polyps and adenomas were more frequently detected in the MC group than in the control group. In a meta-analysis of five studies, a significantly higher prevalence of hyperplastic/inflammatory polyps and adenomas was reported in the MC group than in the control group, while the incidence of adenocarcinoma was not significantly different between the two groups. Although hyperplastic polyps and adenomas were more frequently detected in MC patients, MC was not associated with an elevated risk of colorectal cancer.

Risk of Colorectal Cancer in Serrated Polyposis Syndrome: A Systematic Review and Meta-analysis

Serrated polyposis syndrome (SPS) is characterized by development of numerous serrated lesions throughout the colorectum and increased risk of colorectal cancer (CRC). However, SPS has been an underrecognized CRC predisposition syndrome, and the true risk of CRC in SPS, both overall and in surveillance, is not known. The aim of this systematic review and meta-analysis is to describe the risk of CRC in patients with SPS. Electronic databases were searched on March 25, 2021, for studies describing CRC risk in SPS. Random-effects meta-analysis was performed to assess pooled risk of CRC among SPS patients. Primary outcomes were risk of CRC at time of SPS diagnosis and during surveillance following diagnosis of SPS. Secondary outcomes included risk of CRC prior to diagnosis of SPS and effect of World Health Organization subtype on CRC risk. Thirty-six studies including 2788 patients with SPS were included in the analysis. Overall risk of CRC in SPS was 19.9% (95% confidence interval [CI], 15.3%-24.5%). CRC risk at the time of diagnosis was 14.7% (95% CI, 11.4%-18.8%), while risk during surveillance was 2.8% (95% CI, 1.8%-4.4%), or 7 cases per 1000 person-years. SPS patients also had a high incidence of history of CRC prior to SPS diagnosis (7.0%; 95% CI, 4.6%-11.7). Subgroup analysis did not reveal any significant differences based on World Health Organization subtype. Our meta-analysis demonstrated that patients with SPS have an elevated risk of CRC, which is highest at the time of diagnosis and suggests the importance of early SPS recognition and screening to modify CRC risk. The persistently elevated CRC risk during surveillance supports current guidelines recommending heightened surveillance protocols.

Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease–Associated Colorectal Cancer

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial-mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5'untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.

Long-Term Incidence of Advanced Colorectal Neoplasia in Patients with Serrated Polyposis Syndrome: Experience in a Single Academic Centre

Simple SummarySerrated polyposis syndrome is characterized by the development of large and/or multiple serrated polyps throughout the colorectum and is associated with an increased risk of colorectal cancer (CRC). Even though CRC incidence is low under adequate endoscopic follow-up, a substantial risk of advanced neoplasia (AN) has been described. Nevertheless, very few studies have focused on long-term surveillance. The main aim of this study was to evaluate the incidence of AN in a single-centre cohort followed over 10 years. Within endoscopic surveillance we did not find any CRC and we observed that five-year cumulative incidences of AN were much lower than in other studies. However, a significant reduction of these incidences during follow-up was not proven. Individuals at higher risk of AN were those who fulfilled both 2010 WHO criteria I and III. Our results suggest that at least patients at lower risk might benefit from the extension of surveillance intervals.Serrated polyposis syndrome (SPS) implies a slightly elevated risk of colorectal cancer (CRC) during endoscopic follow-up, but its natural course is still not well known. The main objective of this study was to describe the long-term risk of developing advanced neoplasia (AN) in these patients. Until October 2020, individuals who fulfilled 2010 WHO criteria I and/or III for SPS were retrospectively recruited. We selected those under endoscopic surveillance after resection of all lesions >3 mm in a high-quality colonoscopy. We excluded patients with total colectomy at diagnosis and those with any interval between colonoscopies >3.5 years. We defined AN as advanced serrated polyp (≥10 mm and/or with dysplasia), advanced adenoma, or CRC. In 109 patients, 342 colonoscopies were performed (median = 3, median interval = 1.8 years) during a median follow-up after colonic clearance of 5.0 years. Five-year cumulative incidences of AN were 21.6% globally, and 5.6%, 10.8%, and 50.8% in patients who fulfilled criterion I, III, and both, respectively (p < 0.001). No CRC was diagnosed and only 1 (0.9%) patient underwent surgery. In conclusion, cumulative incidences of AN could be lower than previously described, at least in patients who fulfil the 2010 WHO criterion III alone. Therefore, low-risk individuals might benefit from less stringent surveillance.

The significant interaction between age and diabetes mellitus for colorectal cancer: Evidence from NHANES data 1999–2016

BackgroundDiabetes mellitus has been associated with elevated risk of colorectal cancer (CRC), although interaction between age and DM is unclear. We examined the relationship among DM, CRC and age. Methods22,580 subjects aged ≥18 years were identified from the National Health and Nutrition Examination Survey (NHANES) database collected between 1999–2016. To account for the complex, stratified, multistage probability sampling design in NHANES, SASv9.4 Procedure Survey Methodology was applied. Univariate analysis compared individual baseline characteristics between subjects with and without DM. Multivariate logistic regression model assessed association between DM and CRC, in which the model included factors with p<0.05 in univariate analysis as covariates. ResultsUnivariate analysis showed significant differences in age (p<0.0001), race (p<0.0001), smoking (p=0.0023) and body mass index (p<0.0001) between No-DM and DM. Multivariate analysis revealed significant interaction between age and DM (p=0.0004). Subjects with DM aged 18–65 were more likely to experience CRC (OR=4.47, 95%CI=(1.33–15.07); p=0.0157) compared to those without DM. Subjects with DM aged >65 were not at increased risk for CRC (OR=0.83, 95%CI=(0.43–1.59); p=0.5665) compared to those without DM. ConclusionsAge, DM, and interaction between age and DM are risk factors for CRC. Individuals with DM aged 18–65 years have a higher CRC risk.

COVID concerns highlight the importance of adequate fecal immunochemical test sample collection.

COVID concerns highlight the importance of adequate fecal immunochemical test sample collection.

Risk of colorectal cancer in depressed patients, negative life events, and the prevalence rate of depressive symptoms: a case-control study

Objective: This study aimed at investigating the risk of Colorectal Cancer (CRC) among depressed and Negative Life Events (NLEs) people and the prevalence of depressive symptoms. Materials and Methods: A case-control study was performed from the Colonoscopy Unit of the Cancer Institute in Tabriz. A total of 207 cases with confirmed pathology findings and 207 controls, at the same time for the cases, were included. Multiple logistic regression was used to estimate the adjusted odds ratios and 95 confidence intervals. Results: In the final multiple variable models, depression was associated with CRC insignificantly (OR=1.42, 95 CI: 0.92-2.21); however, NLEs were associated with CRC risk (OR=1.84, 95 CI: 1.08-3.16). Likewise, family history of CRC, diabetes, and smoking were associated with an elevated risk of CRC. Moreover, the prevalence rate () of depressive symptoms among cases and controls was revealed as 11-8 severe, 19-14 moderate, 27-24 mild and 43-54 minimal, respectively. Conclusions: There was a significant positive association between CRC and NLEs while no evidence found that depression increases the risk of CRC.

Transmission Jeopardy of Adenomatosis Polyposis Coli and Methylenetetrahydrofolate Reductase in Colorectal Cancer.

Colorectal cancer (CRC) is one of the globally prevalent and virulent types of cancer with a distinct alteration in chromosomes. Often, any alterations in the adenomatosis polyposis coli (APC), a tumor suppressor gene, and methylenetetrahydrofolate reductase (MTHFR) gene are related to surmise colorectal cancer significantly. In this study, we have investigated chromosomal and gene variants to discern a new-fangled gene and its expression in the southern populations of India by primarily spotting the screened APC and MTHFR variants in CRC patients. An equal number of CRC patients and healthy control subjects (n = 65) were evaluated to observe a chromosomal alteration in the concerted and singular manner for APC and MTHFR genotypes using standard protocols. The increasing prognosis was observed in persons with higher alcoholism and smoking (P < 0.05) with frequent alterations in chromosomes 1, 5, 12, 13, 15, 17, 18, 21, and 22. The APC Asp 1822Val and MTHFR C677T genotypes provided significant results, while the variant alleles of this polymorphism were linked with an elevated risk of CRC. Chromosomal alterations can be the major cause in inducing carcinogenic outcomes in CRCs and can drive to extreme pathological states.

Matrix metalloproteinase-8 rs11225395 polymorphism correlates with colorectal cancer risk and survival in a Chinese Han population: a case-control study.

Matrix metalloproteinase-8 (MMP-8) is a gene associated with inflammation and prognosis in colorectal cancer (CRC). Here, we studied the link between the rs11225395 polymorphism of MMP-8 gene and CRC risk. We recruited 551 CRC cases and 623 controls from among a subpopulation of Han Chinese patients. Data found that this variant was connected to an increased risk of CRC (TT versus CC: OR, 1.76; 95%CI, 1.09–2.84; P = 0.021; T versus C: OR, 1.29; 95%CI, 1.07–1.56; P = 0.007). Stratified analyses indicated a positive association among smokers (TT versus CC: OR, 2.31; 95%CI, 1.12–4.79; P = 0.024), males, and patients ≥ 60 years old. Crossover analysis showed that the potential interaction between smoking or drinking and the MMP-8 rs11225395 polymorphism was related to elevated risk for CRC. The rs11225395 polymorphism was also connected with lymph node metastasis and TNM stage. Moreover, the CRC cases carrying a TT genotype of MMP-8 rs11225395 presented had poorer overall survival than the CC genotype carriers. These findings show that MMP-8 rs11225395 correlates with an elevated risk of CRC and poor patient prognosis in a subpopulation of the Han Chinese subpopulation. Thus, the MMP-8 rs11225395 polymorphism could potentially function as a biomarker predictive of CRC susceptibility.

Effects of taurocholic acid metabolism by gut bacteria: A controlled feeding trial in adult African American subjects at elevated risk for colorectal cancer

Colorectal cancer (CRC) is the third leading cause of cancer and second leading cause of cancer death in the United States. Recent evidence has linked a high fat and animal protein diet and microbial metabolism of host bile acids as environmental risk factors for CRC development. We hypothesize that the primary bile salt taurocholic acid (TCA) is a key, diet-controlled metabolite whose use by bacteria yields a carcinogen and tumor-promoter, respectively. The work is motivated by our published data indicating hydrogen sulfide (H2S) and secondary bile acid production by colonic bacteria, serve as environmental insults contributing to CRC risk. The central aim of this study is to test whether a diet high in animal protein and saturated fat increases abundance of bacteria that generate H2S and pro-inflammatory secondary bile acids in African Americans (AAs) at high risk for CRC. Our prospective, randomized, crossover feeding trial will examine two microbial mechanisms by which an animal-based diet may support the growth of TCA metabolizing bacteria. Each subject will receive two diets in a crossover design― an animal-based diet, rich in taurine and saturated fat, and a plant-based diet, low in taurine and saturated fat. A mediation model will be used to determine the extent to which diet (independent variable) and mucosal markers of CRC risk and DNA damage (dependent variables) are explained by colonic bacteria and their functions (mediator variables). This research will generate novel information targeted to develop effective dietary interventions that may reduce the unequal CRC burden in AAs.

Abstract A16: Environmental exposure to persistent organic pollutants (POPs) and primary colorectal cancer risk: A case-cohort study in a community-based perspective cohort

Abstract Background: Recent studies suggest that the low-dose environmental exposure of persistent organic pollutants (POPs) may develop prostate cancer or breast cancer based on prospective cohort study design. This study investigates a relationship between environmental exposures to POPs and the development of colorectal cancer (CRC) in the general population. Methods: We conducted a case-cohort study based on the Korean National Cancer Center Community Cohort, which included 16,304 adults who enrolled from 1993 to 2010 and followed by 2016 for the cancer incidence. We included 104 CRC cases and 235 adults in a subcohort and assessed their serum lipid-adjusted levels of 19 organochlorine pesticides (OCPs) and 32 polychlorinated biphenyls (PCBs). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for determining the association between POPs and risk of CRC were estimated using logistic regression analyses, controlling for following covariates: age, sex, education, physical activity, meat consumption, vegetable/fruit consumption, drinking, smoking, obesity, pesticides use experience, and residential areas. Results: Natural log-transformed cis-heptachlor epoxide and p,p’-DDD were significantly associated with increased risk of CRC [ORcis-heptachlor epoxide = 1.29, 95% CI: 1.03-1.62; ORp,p’-DDD = 1.63, 95% CI: 1.11-2.41] and increased ORs were also estimated for the highest versus lowest tertiles of these two metabolites [ORcis-heptachlor epoxide = 2.64, 95% CI: 1.24-5.6, p-trend = 0.021; ORp,p’-DDD = 3.51, 95% CI: 1.58-7.78, p-trend = 0.004]. Also, there was a significant association between natural log-transformed PCB 52 and risk of CRC (ORPCB 52 = 1.54, 95% CI: 1.06-2.24). Conclusion: Higher exposure to POPs, such as cis-heptachlor epoxide, p,p’-DDD, and PCB 52, was associated with the elevated risk of CRC. Our findings from a community-based prospective cohort provide evidence on the relationship between environmental exposure of POPs and CRC in the general population. Citation Format: Jinsun Kim, Eun Young Park, Byungmi Kim, Min Kyung Lim, Jin-Kyoung Oh. Environmental exposure to persistent organic pollutants (POPs) and primary colorectal cancer risk: A case-cohort study in a community-based perspective cohort [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A16.

Abstract PR04: Exposure-based assessment and economic valuation of adverse birth outcomes and cancer risk due to nitrate in United States drinking water

Abstract Background: Nitrate ingestion from drinking water has been associated with an increased risk of adverse birth outcomes as well as elevated risk of colorectal cancer and several other cancers. Yet, to date no studies have attempted to quantify the health and economic impacts due to nitrate in drinking water in the United States. Methods: This study presents a first-of-its-kind comprehensive assessment of nitrate exposure from drinking water for the entire United States population. This exposure assessment serves as the basis for our analysis of the annual nitrate-attributable disease cases in the United States and the associated economic losses due to medical costs and lost productivity. Additionally, through a meta-analysis of studies on drinking water nitrate and colorectal cancer, we examine the exposure-response relationship for nitrate and cancer risk. Results: On the basis of national nitrate occurrence data and relative risk ratios reported in the epidemiology literature, we calculated that annually, 2,939 cases of very low birth weight, 1,725 cases of very preterm birth, and 41 cases of neural tube defects could be related to nitrate exposure from drinking water. For cancer risk, combining nitrate-specific risk estimates for colorectal, ovarian, thyroid, kidney, and bladder cancers results in a range of 2,300 to 12,594 annual nitrate-attributable cancer cases (mean: 6,537 estimated cases). For medical expenditures alone, this burden of cancer corresponds to an annual economic cost of $250 million to $1.5 billion U.S. dollars, together with a potential $1.3 to $6.5 billion impact due to lost productivity. With the meta-analysis of eight studies of drinking water nitrate and colorectal cancer, we observed a statistically significant positive association for nitrate exposure and colorectal cancer risk and calculated a one-in-one million cancer risk level of 0.14 mg/L nitrate in drinking water. Conclusion: Health and economic analyses presented here suggest that lowering exposure to nitrate in drinking water could bring economic benefits by alleviating the impacts of nitrate-associated diseases. This abstract is also being presented as Poster A44. Citation Format: Alexis Temkin, Sydney Evans, Tatiana Manidis, Chris Campbell, Olga V. Naidenko. Exposure-based assessment and economic valuation of adverse birth outcomes and cancer risk due to nitrate in United States drinking water [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr PR04.

Abnormal bowel movement frequency increases the risk of rectal cancer: evidence from cohort studies with one million people.

Previous studies from case–control studies failed to draw reliable conclusions regarding the relationship between bowel movement frequency and the risk of colorectal cancer. To further examine this relationship, we collect the data from cohort studies that make a more accurate estimation. Several online data were searched from inception to February 29, 2020. Ten cohort studies involving 1,038,598 individuals were included in our study. The pooled results indicated that a bowel movement of less than once per day was not associated with the risk of colorectal cancer (relative risk (RR)= 1.00, 95% confidence interval (CI): 0.87–1.16, P = 0.950) compared with that of once per day. Compared with a bowel movement frequency of once per day, a bowel movement of more than once per day was also not related to elevated risk of colorectal cancer (RR = 1.04, 95% CI: 0.91–1.19, P = 0.570). The subgroup analyses indicated a low or high bowel movement frequency did not increase the risk of colon cancer (RR = 0.91, 95% CI: 0.80–1.03, P = 0.130). However, an increased frequency of bowel movements increased the risk of rectal cancer (RR = 1.34, 95% CI: 1.19–1.52, P < 0.001). The sensitivity analysis still supports the results. No significant publication bias existed. The data from cohort indicated that less bowel movement frequency was not associated with the risk of colorectal cancer. The frequency of bowel movement affects the risk of rectal cancer.

Fat mass and obesity-associated gene polymorphisms, pre-diagnostic plasma adipokine levels and the risk of colorectal cancer: The Japan Public Health Center-based Prospective Study.

Although their functional outcomes remain largely unknown, single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated gene (FTO) may interact with adipokines, especially leptin and adiponectin, to modify the risk of colorectal cancer. We conducted a prospective study of 375 colorectal cancer cases and 750 matched controls to examine the effects of SNPs in the FTO, either alone or in interaction with pre-diagnostic plasma adipokine levels. Using a conditional logistic regression model, we obtained odds ratios (ORs) and their 95% confidence intervals (CIs) of colorectal cancer. Seven SNPs in strong linkage disequilibrium demonstrated a similarly positive association with colorectal cancer, and most evidently for rs1558902, rs8050136, rs3751812, and rs9939609 (Ptrend = 0.02). Of interest, we observed a statistically significant interaction of rs8050136 with plasma total adiponectin levels (Pinteraction = 0.03). Compared to non-carriers in the lowest quintile of plasma total adiponectin, A allele carriers in the same quintile showed a considerably elevated risk of colorectal cancer, with a body mass index-adjusted OR of 2.54 (95% CI, 1.36–4.75). This investigation of the interaction between SNPs in the FTO and pre-diagnostic plasma adipokine levels has revealed the importance of both genetic and hormonal factors associated with adiposity in colorectal carcinogenesis.

Dietary mercury intake and colorectal cancer risk: A case-control study.

The main source of mercury exposure is food such as fish and shellfish. Mercury is a growing concern due to its associations with a number of harmful health effects, including cancer. The objectives of this study were to examine the association between dietary mercury intake and colorectal cancer (CRC) risk and to determine whether this association differs by anatomical site and menopausal status. A case-control study was conducted with 2769 participants (923 cases and 1846 controls) in Korea. Dietary mercury intake and fish and shellfish consumption were assessed using a semiquantitative food frequency questionnaire. A high intake of dietary mercury was associated with an increased risk of CRC (in the group with lower fish and shellfish consumption; odds ratio (OR): 3.13; 95% confidence interval (95% CI): 2.33, 4.71, in the group with higher fish and shellfish intake; OR: 3.84, 95% CI: 2.20, 7.30) after adjusting for all potential confounders by anatomic site in men. Among women, the results differed by fish and shellfish consumption and menopausal status. Regarding the amount of fish and shellfish intake, a positive association was found only in the group with lower intake (CRC; OR: 2.24, 95% CI: 1.36, 3.72, colon cancer; OR: 2.25, 95% CI: 1.22, 4.16, rectal cancer; OR: 2.28, 95% CI: 1.13, 4.57). In the stratified analysis by menopausal status, the elevated risk of CRC was still observed among both pre- and postmenopausal women depending on anatomical site, except for the colon cancer patients with premenopausal status. A high intake of mercury was associated with an elevated risk of overall CRC. Future large-scale prospective cohort studies are recommended to investigate the causal effects of dietary mercury intake by fish and shellfish consumption on CRC risk depending on anatomical site and menopausal status.

Changes in colorectal cancer screening use after introduction of alternative screening offer in Germany: Prospective cohort study.

In October 2002, screening colonoscopy was added to the German colorectal cancer (CRC) screening program as an alternative to fecal occult blood test (FOBT). We aimed to evaluate the change in CRC screening use after introduction of the dual screening offer and to assess determinants of screening use. Data were drawn from a population-based cohort study initiated during 2000-2002 in Germany (n = 5,845, age range at recruitment: 50-75 years). We conducted both cross-sectional and longitudinal analyses to obtain uptake rates of CRC screening based on four waves of data. Age-group specific proportions of participants having had FOBT within 2 years remained essentially unchanged at 61-67% between 2000 and 2002 (1st wave) and 2005-2007 (3rd wave). The proportions of participants having undergone screening colonoscopy within 10 years increased from 23-29% to 46-57%, leading to a substantial overall increase in being up-to-date with CRC screening from 66-68% to 77-80%. In 2008-2010 (4th wave), FOBT use declined and colonoscopy use continued to increase. Obesity was significantly associated with lower prevalence of being up-to-date with FOBT (odds ratio [OR] at 8-year follow-up 0.68; 95% confidence interval [CI], 0.58-0.80) and screening colonoscopy (OR, 0.73; 95% CI, 0.62-0.86). Also, smokers were less likely to have ever used FOBT (OR, 0.54; 95% CI, 0.40-0.75) or colonoscopy (OR, 0.75; 95% CI, 0.63-0.90) compared to nonsmokers. After the introduction of dual screening offer, the overall adherence to CRC screening steeply increased, mainly due to an increase in screening colonoscopy uptake. Screening tests kept being underused by obese people and smokers who are at elevated CRC risk.

Exposure-based assessment and economic valuation of adverse birth outcomes and cancer risk due to nitrate in United States drinking water.

BackgroundNitrate ingestion from drinking water has been associated with an increased risk of adverse birth outcomes as well as elevated risk of colorectal cancer and several other cancers. Yet, to date, no studies have attempted to quantify the health and economic impacts due to nitrate in drinking water in the United States. MethodsThis study presents a first-of-its-kind comprehensive assessment of nitrate exposure from drinking water for the entire United States population. This exposure assessment serves as the basis for our analysis of the annual nitrate-attributable disease cases in the United States and the associated economic losses due to medical costs and lost productivity. Additionally, through a meta-analysis of studies on drinking water nitrate and colorectal cancer, we examine the exposure-response relationship for nitrate and cancer risk. ResultsOn the basis of national nitrate occurrence data and relative risk ratios reported in the epidemiology literature, we calculated that annually, 2939 cases of very low birth weight, 1725 cases of very preterm birth, and 41 cases of neural tube defects could be related to nitrate exposure from drinking water. For cancer risk, combining nitrate-specific risk estimates for colorectal, ovarian, thyroid, kidney, and bladder cancers results in a range of 2300 to 12,594 annual nitrate-attributable cancer cases (mean: 6537 estimated cases). For medical expenditures alone, this burden of cancer corresponds to an annual economic cost of 250 million to 1.5 billion U.S. dollars, together with a potential 1.3 to 6.5 billion dollar impact due to lost productivity. With the meta-analysis of eight studies of drinking water nitrate and colorectal cancer, we observed a statistically significant positive association for nitrate exposure and colorectal cancer risk and calculated a one-in-one million cancer risk level of 0.14 mg/L nitrate in drinking water. ConclusionHealth and economic analyses presented here suggest that lowering exposure to nitrate in drinking water could bring economic benefits by alleviating the impacts of nitrate-associated diseases.

Meta-analysis of 16 studies of the association of alcohol with colorectal cancer.

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.