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Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure., Methods: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk., Results: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility., Conclusions: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention., Competing Interests: S.G.: Brogent International LLC, co-founder, not related to submitted work. J.B.: co-founder and employee of BioRealm LLC. BioRealm LLC offers data analysis services, unrelated to this study. M.G.: Research funding from Servier and Janssen, unrelated to this study. Other authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Folate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer., Objective: We examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to somatic mutations in genes linked to CRC using targeted sequencing., Design: Participants within 2 large CRC consortia with available information on dietary folate, supplemental folic acid, and total folate intake were included. Colorectal tumor samples from cases were sequenced for the presence of nonsilent mutations in 105 genes and 6 signaling pathways (IGF2/PI3K, MMR, RTK/RAS, TGF-β, WNT, and TP53/ATM). Multinomial logistic regression models were analyzed comparing mutated/nonmutated CRC cases to controls to compute multivariable-adjusted odds ratios (ORs) with 95% confidence interval (CI). Heterogeneity of associations of mutated compared with nonmutated CRC cases was tested in case-only analyses using logistic regression. Analyses were performed separately in hypermutated and nonhypermutated tumors, because they exhibit different clinical behaviors., Results: We included 4339 CRC cases (702 hypermutated tumors, 16.2%) and 11,767 controls. Total folate intake was inversely associated with CRC risk (OR = 0.93; 95% CI: 0.90, 0.96). Among hypermutated tumors, 12 genes (AXIN2, B2M, BCOR, CHD1, DOCK3, FBLN2, MAP3K21, POLD1, RYR1, TET2, UTP20, and ZNF521) showed nominal statistical significance (P < 0.05) for heterogeneity by mutation status, but none remained significant after multiple testing correction. Among these genetic subtypes, the associations between folate variables and CRC were mostly inverse or toward the null, except for tumors mutated for DOCK3 (supplemental folic acid), CHD1 (total folate), and ZNF521 (dietary folate) that showed positive associations. We did not observe differential associations in analyses among nonhypermutated tumors, or according to the signaling pathways., Conclusions: Folate intake was not differentially associated with CRC risk according to mutations in the genes explored. The nominally significant differential mutation effects observed in a few genes warrants further investigation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC., Patients and Methods: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR., Results: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) β, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk., Conclusions: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations., Methods: A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously., Findings: The 3-DF joint test revealed two significant loci with p-value <5 × 10 -8 . Rs4730274 close to the SLC26A3 gene showed an association with fibre (p-value: 2.4 × 10 -3 ) and G × fibre interaction with CRC (OR per quartile of fibre increase = 0.87, 0.80, and 0.75 for CC, TC, and TT genotype, respectively; G × E p-value: 1.8 × 10 -7 ). Rs1620977 in the NEGR1 gene showed an association with fruit intake (p-value: 1.0 × 10 -8 ) and G × fruit interaction with CRC (OR per quartile of fruit increase = 0.75, 0.65, and 0.56 for AA, AG, and GG genotype, respectively; G × E -p-value: 0.029)., Interpretation: We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings., Funding: National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments., Competing Interests: Declaration of interests ESK is a co-investigator in a grant from National Institutes of Health (R01CA196569). JW is Stock shareholder of Gilead Sciences Inc. AK has received consulting fees for Illumina Inc., has participated on data safety monitoring boards or advisory boards of TensorBio, PatchBio, Serimmune, and OpenTargets, and has stock or stock options of Illumina, Freenome, Deep Genomics, Immunai, TensorBio, PatchBio, and Serimmune. MCS was a co-investigator in a grant from National Institutes of Health (R01CA201407). VM has received grant support from Instituto de Salud Carlos III and Fundacion Cientifica Asociación Española Contra el Cáncer. SBG is a co-founder of Brogent international LLC. JPL has received additional grant support (5P01CA196569, 6R01CA201407). The remaining authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769 ), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047 ), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.

Background: The genotoxin colibactin causes a tumor single-base substitution (SBS) mutational signature, SBS88. It is unknown whether epidemiologic factors' association with colorectal cancer risk and survival differs by SBS88., Methods: Within the Genetic Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry, we measured SBS88 in 4,308 microsatellite stable/microsatellite instability low tumors. Associations of epidemiologic factors with colorectal cancer risk by SBS88 were assessed using multinomial regression (N = 4,308 cases, 14,192 controls; cohort-only cases N = 1,911), and with colorectal cancer-specific survival using Cox proportional hazards regression (N = 3,465 cases)., Results: 392 (9%) tumors were SBS88 positive. Among all cases, the highest quartile of fruit intake was associated with lower risk of SBS88-positive colorectal cancer than SBS88-negative colorectal cancer [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.37-0.76; OR = 0.75, 95% CI 0.66-0.85, respectively, Pheterogeneity = 0.047]. Among cohort studies, associations of body mass index (BMI), alcohol, and fruit intake with colorectal cancer risk differed by SBS88. BMI ≥30 kg/m2 was associated with worse colorectal cancer-specific survival among those SBS88-positive [hazard ratio (HR) = 3.40, 95% CI 1.47-7.84], but not among those SBS88-negative (HR = 0.97, 95% CI 0.78-1.21, Pheterogeneity = 0.066)., Conclusions: Most epidemiologic factors did not differ by SBS88 for colorectal cancer risk or survival. Higher BMI may be associated with worse colorectal cancer-specific survival among those SBS88-positive; however, validation is needed in samples with whole-genome or whole-exome sequencing available., Impact: This study highlights the importance of identification of tumor phenotypes related to colorectal cancer and understanding potential heterogeneity for risk and survival., (©2024 American Association for Cancer Research.)

Background: This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks + Escherichia coli (pks + E.coli + ), pks + E.coli - (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum)., Methods: We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR., Results: Pks + E.coli + was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks + E.coli + and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks + E.coli - (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01)., Conclusion: Intratumoral pks + E.coli + but not pks + E.coli - are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause., (© 2024. The Author(s).)

Background: High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations., Methods: A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan., Results: Meta-analyses confirmed positive associations between increased consumption of red meat and processed meat with colorectal cancer risk [per quartile red meat OR = 1.30; 95% confidence interval (CI) = 1.21-1.41; processed meat OR = 1.40; 95% CI = 1.20-1.63]. Two significant genome-wide GxE interactions for red meat consumption were found. Joint GxE tests revealed the rs4871179 SNP in chromosome 8 (downstream of HAS2); greater than median of consumption ORs = 1.38 (95% CI = 1.29-1.46), 1.20 (95% CI = 1.12-1.27), and 1.07 (95% CI = 0.95-1.19) for CC, CG, and GG, respectively. The two-step EDGE method identified the rs35352860 SNP in chromosome 18 (SMAD7 intron); greater than median of consumption ORs = 1.18 (95% CI = 1.11-1.24), 1.35 (95% CI = 1.26-1.44), and 1.46 (95% CI = 1.26-1.69) for CC, CT, and TT, respectively., Conclusions: We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer., Impact: The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups., (©2023 American Association for Cancer Research.)

Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain., Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO)., Findings: A 1-standard deviation (SD:5.1 kg/m 2 ) increment in BMI levels was found to increase risks of Jass type 1 MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10 -5 ) and Jass type 2 non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4 non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3 non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10 -5 ) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03)., Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4)., Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements., Competing Interests: Declaration of interests AB has received a Scholar-in-Training Award from AACR for 2023. VM has received grants from Instituto de Salud Carlos III and FC AECC. BML has received support from Uppsala University as a part of a presentation in the Svedberg Seminar Series, and she was the president of the Australasian Epidemiological Association (2020–2023). BVG has received support grant from World Cancer Research Fund for a separate project within the same research field. AET has received an editorial board fee from NIH PDQ Cancer Genetics. MG has received research funding from Janssen and Servier, consulting fees from Nerviano Medical Sciences, Chromacode, and AstraZeneca and support to attend a meeting from Dava Oncology. JN has received research funding from Natera Inc and consulting fees from Leica Biosciences. MAJ has received an NIH funding. The remaining authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal., Methods: We used univariable and multivariable two-sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self-reported leisure television watching and computer use were identified from a recent genome-wide association study (GWAS). Data related to cancer risk were obtained from cancer GWAS consortia. A series of sensitivity analyses were applied to examine the robustness of the results to the presence of confounding., Results: A 1-standard deviation (SD: 1.5 h/day) increment in hours of television watching increased risk of breast cancer (OR per 1-SD: 1.15, 95% confidence interval [CI]: 1.05-1.26) and colorectal cancer (OR per 1-SD: 1.32, 95% CI: 1.16-1.49) while there was little evidence of an association for prostate cancer risk (OR per 1-SD: 0.94, 95% CI: 0.84-1.06). After adjusting for years of education, the effect estimates for television watching were attenuated (breast cancer, OR per 1-SD: 1.08, 95% CI: 0.92-1.27; colorectal cancer, OR per 1-SD: 1.08, 95% CI: 0.90-1.31). Post hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed for each cancer site according to sex (colorectal cancer), anatomical subsites and cancer subtypes. There was little evidence of associations between genetically predicted computer use and cancer risk., Conclusions: Our univariable analysis identified some positive associations between hours of television watching and risks of breast and colorectal cancer. However, further adjustment for additional lifestyle factors especially years of education attenuated these results. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development., (© 2023 World Health Organization; licensed by John Wiley & Sons Ltd. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC., Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk., Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO)., Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10 -8 ) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10 -8 ). No interactions were observed for dietary and total folate., Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer., Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Physical activity reduces the risk of colorectal cancer (CRC), but the relevant evidence derives primarily from self-reported recreational and occupational activity. Less is known about the contribution of other domains of physical activity, such as transport and household. We examined associations between domain-specific physical activities and CRC risk within the Melbourne Collaborative Cohort Study., Methods: Analyses included 23,586 participants who were free from invasive colorectal cancer and had completed the International Physical Activity Questionnaire-Long Form at follow-up 2 (2003-2007). Cox regression, with age as the time metric, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ordinal categories of each physical activity domain., Results: Adjusted HRs for the highest versus the lowest categories of physical activity were 0.71 (95% CI: 0.51-0.98; p trend  = 0.03) for recreational activity; 0.80 (95% CI: 0.49-1.28; p trend  = 0.38) for occupational activity; 0.90 (95% CI: 0.68-1.19; p trend  = 0.20) for transport activity; and 1.07 (95% CI: 0.82-1.40; p trend  = 0.46) for household activity., Conclusions: Recreational activity was associated with reduced CRC risk. A non-significant, inverse association was observed for occupational activity, whereas no association was found for transport or household domains.

The influence of lifestyle factors on survival following a diagnosis of colorectal cancer (CRC) is not well established. We examined associations between lifestyle factors measured before diagnosis and CRC survival. The Melbourne Collaborative Cohort Study collected data on alcohol intake, cigarette smoking and physical activity, and body measurements at baseline (1990-1994) and wave 2 (2003-2007). We included participants diagnosed to 31 August 2015 with incident stages I-III CRC within 10-years post exposure assessment. Information on tumor characteristics and vital status was obtained. Tumor DNA was tested for microsatellite instability (MSI) and somatic mutations in oncogenes BRAF (V600E) and KRAS. We estimated hazard ratios (HRs) for associations between lifestyle factors and overall and CRC-specific mortality using Cox regression. Of 724 eligible CRC cases, 339 died (170 from CRC) during follow-up (average 9.0 years). Exercise (non-occupational/leisure-time) was associated with higher CRC-specific survival for stage II (HR = 0.25, 95% CI: 0.10-0.60) but not stages I/III disease (p for interaction = 0.01), and possibly for colon and KRAS wild-type tumors. Waist circumference was inversely associated with CRC-specific survival (HR = 1.25 per 10 cm increment, 95% CI: 1.08-1.44), independent of stage, anatomic site and tumor molecular status. Cigarette smoking was associated with lower overall survival, with suggestive evidence of worse survival for BRAF mutated CRC, but not with CRC-specific survival. Alcohol intake was not associated with survival. Survival did not differ by MSI status. We have identified pre-diagnostic predictors of survival following CRC that may have clinical and public health relevance., (© 2017 UICC.)

Financial hardship may affect up to 30% of cancer survivors, however, little research has addressed the effect of employment change on financial hardship. This study compared the self-reported financial hardship of middle-aged (45-64 years) colorectal cancer survivors (n = 187) at 6 and 12 months following diagnosis with that of a matched general population group (n = 355). Colorectal cancer survivors were recruited through the Queensland Cancer Registry, Australia; data from the Household Income and Labour Dynamics in Australia (HILDA) Survey were used for the general population group. Pearson chi-square tests were used to assess the differences in proportions between the two groups and McNemar tests to assess differences across time among the same group. Generalised linear modelling was performed to produce prevalence ratios. A higher proportion of workers with colorectal cancer reported financial strain (money shortage for living essentials) at 6 months (15%) but eased and was comparable to the comparison group at 12 months (7%). Middle-aged working cancer survivors who ceased or reduced work were more likely to report not being financially comfortable, compared with those who had continued work (adjusted prevalence ratio 1.66, 95%CI: 1.12, 2.44) at 12 months. Health professionals, employers and government services should address the impact of impaired employment on financial hardship among cancer survivors., (© 2017 John Wiley & Sons Ltd.)

Objective: This study aimed to examine the association between change in employment participation for a 12-month period and quality of life among individuals with colorectal cancer compared with general population controls., Methods: This was a prospective, registry-based study that enrolled middle-aged (45-64 years) residents of Queensland, Australia, who were in the paid workforce, and newly diagnosed with colorectal cancer. Participants completed structured telephone interviews at 6 and 12 months after diagnosis assessing quality of life and employment status ("retired/ceased work," "increased work," "decreased work," and "maintained work"). Survivors were matched on demographic and occupation characteristics in a 1:2 ratio with individuals from the general population who had participated in both Wave 10 (2010) and 11 (2011) of the Household, Income and Labour Dynamics in Australia survey., Results: Almost half (66/148, 45%) of colorectal cancer survivors ceased or decreased work during the study period, compared with 27% in the control group (79/295, P = .001). Physical and mental well-being did not fluctuate over time in the general population. However, there were significant improvements in physical well-being, functional well-being, and overall quality of life during the study period for participants with colorectal cancer. At 12 months postdiagnosis, participants with colorectal cancer who maintained or increased work had significantly better functional well-being and overall quality of life compared with those who decreased work or retired., Conclusions: A diagnosis of colorectal cancer often impairs the ability of a person to maintain work. The impairments are predominantly physical and functional. Interventions to assist with occupational rehabilitation should be trialed., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Colorectal cancer affects a wide range of working-age people. Little is known about the consequent work limitations., Objective: The aim of this study was to understand the extent and changing nature of work-related limitations of middle-aged (45-64 years) people over the first 12 months of colorectal cancer., Methods: Surveys were administered to participants recruited via the Queensland Cancer Registry, at 6 and 12 months after diagnosis. Among those who returned to work, the Work Limitations Questionnaire measured 4 job performance domains (time management, physical, mental-interpersonal, and output demands) and an overall productivity score. Open-ended questions supplemented the Work Limitations Questionnaire, and responses were thematically analyzed., Results: Of 239 participants, 8% did not continue in the study, and 20% left employment by 12 months, leaving 171 participants eligible for this analysis. Open-ended responses for why participants stopped work included bowel problems and stoma, loss of strength, and medication adverse effects. At 12 months, 22% to 39% of participants reported work limitations, but there was no overall significant change in work limitations between 6 and 12 months. Qualitative data highlighted the key work-related issues were changes in work functioning, attitudes of employers and colleagues, financial pressures, and emotional responses., Conclusions: While a significant proportion left work because of treatment-related problems, and the majority of participants did not experience workplace limitations, some reported considerable work-related challenges., Implications for Practice: Discussions with health professionals about the possible impact of treatment adverse effects on employment, good communication with employers, and workplace flexibility may facilitate return to work for this population.

Purpose: Engaging in positive health behaviours can improve quality of life amongst cancer survivors, whether this facilitates return to work is unknown. We examined associations of health behaviours with return to work outcomes following a diagnosis of colorectal cancer in middle-aged men and women (45-64 years)., Methods: We recruited 239 participants through the Queensland Cancer Registry between January 2010 and September 2011. Data were collected through telephone-administered interviews and postal questionnaires at 6 and 12 months post-diagnosis. Logistic regression examined likelihood of ceasing or reducing work, and Cox regression examined factors associated with time to return to work., Results: No significant associations were observed between health behaviours (fruit and vegetables consumption, alcohol consumption, smoking status, physical activity or sitting time) at 6 months and ceasing or reducing work at 12 months post-diagnosis. Participants who reported excessive sleep (≥9 h/day) were 2.69 times more likely to reduce work time or retire (relative to those sleeping the recommended 7 to <9 h/day; 95 % CI 1.06, 6.87, adjusted for cancer treatment). In Cox regression analysis, excessive sleep was associated with a longer work re-entry time (relative to sleeping 7 to <9 h/day; HR = 0.47; 95 % CI 0.22, 1.00, adjusted for education and cancer treatment)., Conclusions: Further research into how excessive sleep might be related to return to work amongst colorectal cancer survivors is warranted. Interventions focused on achieving optimal sleep patterns may assist colorectal cancer survivors to return to work and should be tested in future studies.

Purpose: Physical activity improves the health outcomes of colorectal cancer (CRC) survivors, yet few are exercising at levels known to yield health benefits. Baseline demographic, clinical, behavioral, and psychosocial predictors of physical activity at 12 months were investigated in CRC survivors., Methods: Participants were CRC survivors (n = 410) who completed a 12-month multiple health behavior change intervention trial (CanChange). The outcome variable was 12 month sufficient physical activity (≥150 min of moderate-vigorous physical activity/week). Baseline predictors included demographics and clinical variables, health behaviors, and psychosocial variables., Results: Multivariate linear regression revealed that baseline sufficient physical activity (p < 0.001), unemployment (p = 0.004), private health insurance (p = 0.040), higher cancer-specific quality of life (p = 0.031) and higher post-traumatic growth (p = 0.008) were independent predictors of sufficient physical activity at 12 months. The model explained 28.6% of the variance., Conclusions: Assessment of demographics, health behaviors, and psychosocial functioning following a diagnosis of CRC may help to develop effective physical activity programs., Implications for Cancer Survivors: Understanding the demographic, behavioral and psychosocial determinants of physical activity may facilitate the development and delivery of effective public health interventions designed to promote long term behavior change., Trial Registration: ACTRN12608000399392.

Background: Few studies have been undertaken to understand the employment impact in patients with colorectal cancer and none in middle-aged individuals with cancer. This study described transitions in, and key factors influencing, work participation during the 12 months following a diagnosis of colorectal cancer., Methods: We enrolled 239 adults during 2010 and 2011 who were employed at the time of their colorectal cancer diagnosis and were prospectively followed over 12 months. They were compared to an age- and gender-matched general population group of 717 adults from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data were collected using telephone and postal surveys. Primary outcomes included work participation at 12 months, changes in hours worked and time to work re-entry. Multivariable logistic and Cox proportional hazards models were undertaken., Results: A significantly higher proportion of participants with colorectal cancer (27%) had stopped working at 12 months than participants from the comparison group (8%) (p < 0.001). Participants with cancer who returned to work took a median of 91 days off work (25-75 percentiles: 14-183 days). For participants with cancer, predictors of not working at 12 months included: being older, lower BMI and lower physical well-being. Factors related to delayed work re-entry included not being university-educated, working for an employer with more than 20 employees in a non-professional or managerial role, longer hospital stay, poorer perceived financial status and having or had chemotherapy., Conclusions: In middle-adulthood, those working and diagnosed with colorectal cancer can expect to take around three months off work. Individuals treated with chemotherapy, without a university degree and from large employers could be targeted for specific assistance for a more timely work entry., Trial Registration: ACTRN12611000530921.

Background: Sedentary behavior may independently contribute to morbidity and mortality among survivors of colorectal cancer. In the current study, the authors assessed whether a telephone-delivered multiple health behavior change intervention had an effect on the sedentary behavior of recently diagnosed colorectal cancer survivors., Methods: A total of 410 participants were recruited through the Queensland Cancer Registry and randomized to the health coaching (intervention) or usual-care (control) group. Eleven health coaching sessions addressing multiple health behaviors, including sedentary behavior, were delivered over a period of 6 months. Data were collected at baseline (before randomization), at 6 months, and at 12 months via a telephone interview., Results: At 12 months, there was a significant decrease noted in the hours per day of sedentary time in both the health coaching (-1.21; 95% confidence interval [95% CI], -1.71 to -0.70) and usual-care groups (-0.55; 95% CI, -1.06 to -0.05), but the between-group difference was not found to be statistically significant (-0.65; 95% CI, -1.37 to 0.06 [P = .07]). In stratified subgroup analyses, the multiple health behavior change intervention was found to have a significant effect on total sedentary time (hours/day) at 12 months in survivors of colorectal cancer who were aged > 60 years (-0.90; 95% CI, -1.80 to -0.01 [P = .05]), male (-1.33; 95% CI, -2.44 to -0.21 [P = .02]), and nonobese (-1.10; 95% CI, -1.96 to -0.25; [P = .01])., Conclusions: Incorporating simple messages about limiting sedentary behaviors into a multiple health behavior change intervention was found to have modest effects on sedentary behavior. A sedentary behavior-specific intervention strategy may be required to achieve substantial changes in sedentary behavior among colorectal cancer survivors., (© 2014 American Cancer Society.)

Purpose: Colorectal cancer survivors are at risk for poor health outcomes because of unhealthy lifestyles, but few studies have developed translatable health behavior change interventions. This study aimed to determine the effects of a telephone-delivered multiple health behavior change intervention (CanChange) on health and behavioral outcomes among colorectal cancer survivors., Methods: In this two-group randomized controlled trial, 410 colorectal cancer survivors were randomly assigned to the health coaching intervention (11 theory-based telephone-delivered health coaching sessions delivered over 6 months focusing on physical activity, weight management, dietary habits, alcohol, and smoking) or usual care. Assessment of primary (ie, physical activity [Godin Leisure Time Index], health-related quality of life [HRQoL; Short Form-36], and cancer-related fatigue [Functional Assessment of Chronic Illness Therapy Fatigue Scale]) and secondary outcomes (ie, body mass index [kg/m(2)], diet and alcohol intake [Food Frequency Questionnaire], and smoking) were conducted at baseline and 6 and 12 months., Results: At 12 months, significant intervention effects were observed for moderate physical activity (28.5 minutes; P = .003), body mass index (-0.9 kg/m(2); P = .001), energy from total fat (-7.0%; P = .006), and energy from saturated fat (-2.8%; P = .016). A significant intervention effect was reported for vegetable intake (0.4 servings per day; P = .001) at 6 months. No significant group differences were found at 6 or 12 months for HRQoL, cancer-related fatigue, fruit, fiber, or alcohol intake, or smoking., Conclusion: The CanChange intervention was effective for improving physical activity, dietary habits, and body mass index in colorectal cancer survivors. The intervention is translatable through existing telephone cancer support and information services in Australia and other countries.

This study has used the structural equation modelling to examine the role of benefit-finding (BF) in the context of the stress and coping model. In the study, 1276 individuals diagnosed with colorectal cancer completed a written questionnaire and telephone interview at around 4.5 months (on average) and 12 months post-diagnosis. Analyses revealed that the final model fit the data, where stress, coping and BF accounted for 63% of the variance in Time 1 quality of life (QOL). Threat appraisal, coping resources, avoidant coping and BF directly impacted on Time 1 QOL, while threat appraisal, social support and approach coping directly impacted on BF. Approach coping and BF had differential relationships with stress, coping resources and outcomes, indicating that BF may not be a meaning-based coping strategy, as proposed by Folkman [Folkman, S. (1997). Positive psychological states and coping with severe stress. Social Science and Medicine, 45, 1207–1221]. Theoretical and clinical implications are discussed.

Objective: To examine prospective associations of television viewing time with quality of life, following a colorectal cancer diagnosis., Methods: One thousand, nine hundred and sixty-six colorectal cancer survivors were recruited through the Queensland Cancer Registry. Interviews were conducted at 5, 12, 24, and 36 months post-diagnosis. Generalized linear mixed models estimated the effects of television viewing time on quality of life., Results: Participants who watched ≥5 h of television per day had a 16% lower total quality of life score than did participants reporting ≤2 h per day. Deleterious associations of television viewing time were found with all quality of life subscales: functional well-being showed the strongest association (23% difference in quality of life scores between highest and lowest television viewing categories), and social well-being the weakest association (6% difference). Participants who increased their television viewing by one category (e.g., ≤2 h, increasing to 3-4 h per day) had a proportional decrease of some 6% in their quality of life score (intra-individual effect)., Conclusions: The deleterious associations of television viewing time with quality of life were clinically significant and consistent over time. Decreasing sedentary behavior may be an important behavioral strategy to enhance the quality of life of cancer survivors.

Background: The number of middle-aged working individuals being diagnosed with cancer is increasing and so too will disruptions to their employment. The aim of the Working After Cancer Study is to examine the changes to work participation in the 12 months following a diagnosis of primary colorectal cancer. The study will identify barriers to work resumption, describe limitations on workforce participation, and evaluate the influence of these factors on health-related quality of life., Methods/design: An observational population-based study has been designed involving 260 adults newly-diagnosed with colorectal cancer between January 2010 and September 2011 and who were in paid employment at the time they were diagnosed. These cancer cases will be compared to a nationally representative comparison group of 520 adults with no history of cancer from the general population. Eligible cases will have a histologically confirmed diagnosis of colorectal cancer and will be identified through the Queensland Cancer Registry. Data on the comparison group will be drawn from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data collection for the cancer group will occur at 6 and 12 months after diagnosis, with work questions also asked about the time of diagnosis, while retrospective data on the comparison group will be come from HILDA Waves 2009 and 2010. Using validated instruments administered via telephone and postal surveys, data will be collected on socio-demographic factors, work status and circumstances, and health-related quality of life (HRQoL) for both groups while the cases will have additional data collected on cancer treatment and symptoms, work productivity and cancer-related HRQoL. Primary outcomes include change in work participation at 12 months, time to work re-entry, work limitations and change in HRQoL status., Discussion: This study will address the reasons for work cessation after cancer, the mechanisms people use to remain working and existing workplace support structures and the implications for individuals, families and workplaces. It may also provide key information for governments on productivity losses., Study Registration: Australian and New Zealand Clinical Trial Registry No. ACTRN12611000530921.

Aims: To assess self-reported lifetime prevalence of cardiovascular disease (CVD) among colorectal cancer survivors, and examine the cross-sectional and prospective associations of lifestyle factors with co-morbid CVD., Methods: Colorectal cancer survivors were recruited (n=1966). Data were collected at approximately 5, 12, 24 and 36 months post-diagnosis. Cross-sectional findings included six CVD categories (hypercholesterolaemia, hypertension, diabetes, heart failure, kidney disease and ischaemic heart disease (IHD)) at 5 months post-diagnosis. Longitudinal outcomes included the probability of developing (de novo) co-morbid CVD by 36 months post-diagnosis. Lifestyle factors included body mass index, physical activity, television (TV) viewing, alcohol consumption and smoking., Results: Co-morbid CVD prevalence at 5 months post-diagnosis was 59%, and 16% of participants with no known CVD at the baseline reported de novo CVD by 36 months. Obesity at the baseline predicted de novo hypertension (odds ratio [OR]=2.20, 95% confidence intervals [CI]=1.09, 4.45) and de novo diabetes (OR=6.55, 95% CI=2.19, 19.53). Participants watching >4h of TV/d at the baseline (compared with <2h/d) were more likely to develop ischaemic heart disease by 36 months (OR=5.51, 95% CI=1.86, 16.34)., Conclusion: Overweight colorectal cancer survivors were more likely to suffer from co-morbid CVD. Interventions focusing on weight management and other modifiable lifestyle factors may reduce functional decline and improve survival., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: Promoting physical activity among cancer survivors is a high priority. Understanding barriers to physical activity provides an evidence base to inform relevant strategies for doing so., Methods: Telephone interviews were conducted with colorectal cancer survivors at 5 (n = 538) and 12 months post-diagnosis (n = 403). We used an ecological model of health behaviour to classify participants' perceived barriers to physical activity into four sub-categories: physical environment, social environment, personal attributes, and disease-specific barriers., Results: Disease-specific barriers were perceived as the greatest challenge to colorectal cancer survivors being more physically active, closely followed by personal attributes. The physical environment presented the least salient perceived barriers; however, the physical environment was most closely associated with achieving sufficient levels of physical activity at 5 months post-diagnosis. The difficulties most frequently reported by participants at both time points were belief that they were already active enough, not feeling well enough to be physically active, and experiencing fatigue., Conclusions: These findings suggest potential points for intervention to influence physical activity among colorectal cancer survivors.

This longitudinal study investigated relations between benefit-finding domains and outcome measures. Participants were 1,757 individuals diagnosed with colorectal cancer. A written questionnaire and telephone interview were completed at 5-months (Time 1) and 12-months post-diagnosis (Time 2). Exploratory and confirmatory factor analyses revealed three psychometrically sound factors: personal growth, interpersonal growth, and acceptance. Results of regression analyses were conducted and found that Time 1 benefit-finding domains accounted for significant amounts of variance in Time 1 positive affect and cancer-related quality of life (both the aggregate score and its social/family, functional, and colorectal cancer-specific well-being subscales). Time 1 personal growth also predicted Time 1 psychological distress. After controlling for Time 1 positive affect, personal growth continued to predict Time 2 positive affect. Results delineate the benefit-finding domains in the context of colorectal cancer and their differential links with outcome measures cross-sectionally, and longitudinally. These findings have implications for theory building and the measurement of benefit-finding.

Objective: To investigate the prospective relationships between television viewing time and weight gain in the 3 years following colorectal cancer diagnosis for 1,867 colorectal cancer survivors (body mass index (BMI) > or = 18.5 kg/m(2))., Methods: BMI, television viewing time, physical activity, and socio-demographic and clinical covariates were assessed at baseline (5 months), 24 months and 36 months post-diagnosis. Multiple linear regression was used to study independent associations between baseline television viewing time and BMI at 24 and 36 months post-diagnosis., Results: At both follow-up time points, there was a significant increase in mean BMI for participants reporting > or =5 h/day of television viewing compared to those watching <3 h/day at baseline (24 months: 0.72 kg/m(2) (0.31, 1.12), p < 0.001; 36 months: 0.61 kg/m(2) (0.14, 1.07), p = 0.01), independent of baseline BMI, gender, age, education, marital status, smoking, cancer site, cancer disease stage, treatment mode and co-morbidities. Additional adjustment for baseline physical activity did not change results., Conclusions: These findings suggest that a greater emphasis on decreasing television viewing time could help reduce weight gain among colorectal cancer survivors. This, in turn, could contribute to a risk reduction for co-morbid conditions such as type 2 diabetes and cardiovascular disease.

Background: Colorectal cancer survivors may suffer from a range of ongoing psychosocial and physical problems that negatively impact on quality of life. This paper presents the study protocol for a novel telephone-delivered intervention to improve lifestyle factors and health outcomes for colorectal cancer survivors., Methods/design: Approximately 350 recently diagnosed colorectal cancer survivors will be recruited through the Queensland Cancer Registry and randomised to the intervention or control condition. The intervention focuses on symptom management, lifestyle and psychosocial support to assist participants to make improvements in lifestyle factors (physical activity, healthy diet, weight management, and smoking cessation) and health outcomes. Participants will receive up to 11 telephone-delivered sessions over a 6 month period from a qualified health professional or 'health coach'. Data collection will occur at baseline (Time 1), post-intervention or six months follow-up (Time 2), and at 12 months follow-up for longer term effects (Time 3). Primary outcome measures will include physical activity, cancer-related fatigue and quality of life. A cost-effective analysis of the costs and outcomes for survivors in the intervention and control conditions will be conducted from the perspective of health care costs to the government., Discussion: The study will provide valuable information about an innovative intervention to improve lifestyle factors and health outcomes for colorectal cancer survivors., Trial Registration: ACTRN12608000399392.

Objective: This longitudinal study developed and confirmed the factor structure of the 32-item Coping with Colorectal Cancer (CCRC) measure. Reliability and validity of the measure were also assessed., Methods: Participants were 1800 individuals diagnosed with colorectal cancer (CRC). A written questionnaire and a telephone interview were completed at 5 (Time 1) and 12 months post-diagnosis (Time 2)., Results: Exploratory and confirmatory factor analyses revealed eight mostly empirically distinct subscales: Positive Perceptual Change, Religion/Spirituality, Rumination, Acceptance, Humour, Palliative, Seeking Social Support, and Lifestyle Reorganisation. Internal reliabilities were adequate and comparable to other coping measures, and test-retest analyses showed moderate temporal stability of the subscales. Cross-sectional and longitudinal regression analyses were conducted to establish criterion-related validity. As hypothesised, after controlling for demographics, disease/treatment, and stress/coping variables, regression analyses showed that CCRC subscales uniquely predicted Time 1 quality of life (QOL) outcomes (positive affect, cancer-related QOL, psychological distress). After controlling for Time 1 QOL, Seeking Social Support coping continued to predict Time 2 positive affect., Conclusions: Results demonstrated the preliminary validity and reliability of the CCRC subscales, and have extended the cancer coping research by revealing new relations between coping subscales and QOL in a mixed-gender, older population with CRC.

Purpose: Increased physical activity in patients with colorectal cancer is related to improved recurrence-free and overall survival. Psychological distress after cancer may place patients at risk of reduced physical activity, but paradoxically may also act as a motivator for lifestyle change. The relationship between psychological distress and physical activity after cancer over time has not been described., Methods: A prospective survey of 1,966 (57% response) colorectal cancer survivors assessed the psychological distress variables of anxiety, depression, somatization, and cancer threat appraisal as predictors of physical activity at 5, 12, 24, and 36 months postdiagnosis; 978 respondents had valid data for all time points., Results: Higher somatization was associated with greater physical inactivity (relative risk ratio [RRR] = 1.12; 95% CI, 1.1 to 1.2) and insufficient physical activity (RRR = 1.05; 95% CI, 0.90 to 1.0). Respondents with a more positive appraisal of their cancer were significantly (P = .031) less likely to be inactive (RRR = 0.95; 95% CI, 0.90 to 1.0) or insufficiently active (RRR = 0.96). Fatigued and obese respondents and current smokers were more inactive. Respondents whose somatization increased between two time periods were less likely to increase their physical activity over the same period (P < .001). Respondents with higher anxiety at one time period were less likely to have increased their activity at the next assessment (P = .004). There was no association between depression and physical activity., Conclusion: Cancer survivors who experience somatization and anxiety are at greater risk of physical inactivity. The lack of a clear relationship between higher psychological distress and increasing physical activity argues against distress as a motivator to exercise in these patients.

Objective: To investigate the feasibility and short-term effectiveness of a lifestyle intervention for colorectal cancer (CRC) survivors., Methods: CanChange was telephone-delivered to 20 CRC survivors by health coaches over 6 weeks supported by an interactive participant handbook. We assessed program feasibility (program retention and satisfaction) and health outcomes [CRC-specific symptoms (fatigue, nausea, diarrhoea), quality of life (QOL), and lifestyle variables (physical activity, dietary intake, alcohol intake, smoking, body mass index (BMI))] at baseline and post-intervention., Results: Post-intervention, 76% of participants rated the program as excellent, 100% rated the health coach as excellent, and 75% rated the handbook as excellent. In addition, 80% said that CanChange addressed their issues, 72% said that CanChange helped them deal more effectively with their problems, and 100% said that CanChange made them more motivated to make positive life changes. Finally, all participants said that they would recommend CanChange to other CRC survivors. From baseline to post-intervention we observed: non-significant improvements in all CRC-specific symptoms and QOL; a significant decrease in processed meat intake [median (interquartile range): 1.0 (3.0) vs 0.0 (1.0), p=0.01]; as well as non-significant improvements in sedentary behaviour, and the proportion of participants meeting the national guidelines for fruit and vegetable intake. We observed no change in smoking status, while the results for alcohol intake, physical activity, and BMI were variable., Conclusions: CanChange was a feasible and potentially effective lifestyle intervention to improve health outcomes for CRC survivors. A large randomised controlled trial will follow to test the longer-term effects of this approach., ((c) 2009 John Wiley & Sons, Ltd.)

Objective: The present study prospectively assessed the influence of medical, socio-demographic, psychological, and lifestyle variables on physical, social/family, emotional, functional well-being and colorectal cancer-specific concerns in a population-based sample of colorectal cancer survivors., Methods: Participants (n=1822) were assessed at 6 and 24 months post-diagnosis. Predictor variables assessed at 6 months included socio-demographic and medical variables, symptoms/side-effects, body mass index, physical activity, optimism, social support, and cancer threat appraisal. Quality of life (QOL) was assessed at 6 and 24 months post-diagnosis using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C)., Results: For each QOL subscale and for the overall FACT-C scale, 6 month scores were the strongest predictor of QOL scores at 24 months post-diagnosis (e.g. beta=0.447, p < 0.001 for overall QOL). Socio-demographic, medical, and psychosocial variables, but not lifestyle variables, differentially predicted domain specific QOL. Only cancer threat appraisal was associated with all five QOL domains., Conclusion: Cancer threat appraisal presents as a potentially modifiable variable for interventions seeking to improve QOL. Symptom management and lifestyle strategies to ameliorate the effects of co-morbidities, disease stage and troublesome symptoms such as faecal incontinence on QOL should also be included., ((c) 2008 John Wiley & Sons, Ltd.)

Background: How cancer adversely affects an individual's work role is an understudied survivorship issue. There are no Australian studies quantifying work participation after cancer or the potential barriers to work continuance. Using a large, population-based cohort of working adults with colorectal cancer, we assessed changes in work participation separately for men (n=621) and women (n=354)., Methods: Telephone survey methods collected data on colorectal cancer survivors identified through the Queensland Cancer Registry. Status at baseline and one-year post-diagnosis were described, and logistic regression models assessed correlates of work cessation., Results: Among working adults who were diagnosed with colorectal cancer, 33% of men and 40% of women were not working at one-year post-diagnosis. Radiation therapy among men (OR=2.55, 95%CI: 1.35-4.83) and chemotherapy among women (OR=2.49, 95% Cl: 1.23-5.04) were associated with a higher prevalence of work cessation. Having private health insurance was linked with resuming work for both men and women., Conclusion: A large proportion of working men and women leave the workforce by 12 months following a diagnosis of colorectal cancer. Factors correlated with work cessation after colorectal cancer appear different for men and women., Implications: A better understanding of how cancer affects working adults and contributes to unwanted work cessation is required to identify individuals who may benefit from occupational rehabilitation programs.

Goal: A better understanding of health behaviors after a cancer diagnosis is important, as these behaviors are related to physical functioning, disease recurrence, development of second primary cancers, and risk of other chronic diseases. Body weight and health behaviors (smoking status, alcohol consumption, and physical activity) were examined in a population-based sample of colorectal cancer survivors and compared to a matched population group., Materials and Methods: Data were collected by telephone interviews pre-diagnosis (retrospectively reported), 6 and 12 months post-diagnosis for colorectal cancer survivors (n = 1,250). Comparison data were from a population-based cancer risk survey (n = 6,277)., Results: Colorectal cancer survivors were most likely to be overweight/obese pre-diagnosis (66%) than at 6 months (54%) or 12 months post-diagnosis (61%). There was little variation from 6 to 12 months in the proportion of current smokers (7% and 8%, respectively) or high-risk drinkers (both 22%). The greatest changes were for physical activity, with 53% of survivor's sufficiently active pre-diagnosis, 32% at 6 months, and 38% at 12 months post-diagnosis. At 12 months, colorectal cancer survivors were more likely than the comparison group to be: underweight (OR = 2.14, 95% CI = 1.38-3.31); a former smoker (OR = 1.44, 95% CI = 1.26-1.63); a low-risk (OR = 1.25, 95% CI = 1.09-1.44) or high-risk drinker (OR = 1.70, 95% CI = 1.43-2.03); and insufficiently active (OR = 1.57, 95% CI = 1.34-1.83) or inactive (OR = 2.76, 95% CI = 2.39-3.19). However, colorectal cancer survivors were significantly less likely to be a current smoker (OR = 0.68, 95% CI = 0.54-0.85)., Conclusions: Our findings show particular scope for physical activity interventions for colorectal cancer survivors. Improving the general health of cancer survivors should help to decrease morbidity in this population and associated health system expenditure.

Purpose: Physical activity can enhance quality of life for cancer survivors. However, few longitudinal studies have examined whether physical activity has a sustained effect on improvements in quality of life. The present study aims to examine the relationships between physical activity and quality of life over 2 years after a colorectal cancer diagnosis., Patients and Methods: Data were collected within the Colorectal Cancer and Quality of Life Study, in which 1,966 people diagnosed with colorectal cancer were recruited through the Queensland Cancer Registry. Participants completed telephone interviews at approximately 6, 12, and 24 months after diagnosis. Generalized linear mixed models were used to estimate the overall, interindividual, and intraindividual level independent effects of participation in physical activity on quality of life., Results: There was an overall independent association between physical activity and quality of life. At a given time point, participants achieving at least 150 minutes of physical activity per week had an 18% higher quality of life score than those who reported no physical activity. Significant associations were also present at the interindividual level (differences between participants) and intraindividual level (within participant changes)., Conclusion: These findings suggest that the positive association between physical activity and quality of life is consistent over time. Encouraging colorectal cancer survivors to be physically active may be a helpful strategy for enhancing quality of life.

Objective: To investigate the reliability of collecting colorectal stage information from pathology reports and general practitioners in Queensland, Australia., Methods: A longitudinal study of colorectal cancer survivors conducted in 2003 and 2004 (n=1966, response rate=57%) obtained stage information from clinical specialists (n=1334), general practitioners (GP) (n=1417) and by extracting stage from pathology reports (n=1484). Reliability of stage information was determined by comparing stage from GPs and pathology reports with that reported by the clinical specialists, using a weighted kappa., Results: GPs and pathology reports each had a similar level of agreement with clinical specialists, with kappa scores of 0.77 (0.75-0.80) (n=1042) and 0.78 (0.75-0.81) (n=1152), respectively. Results were similar when restricting to records staged by all three methods (n=847). GPs had similar levels of agreement with clinical specialists within each stage, although pathology reports tended to under-stage patients in Stage D (0.37). Collapsing stage into two categories (A or B, C or D) increased the reliability estimates from the pathology reports to 0.91 (0.88-0.93), but there was little change in GP estimates 0.79 (0.75-0.83)., Conclusions: Extractions from pathology reports are a valid source of broad stage information for colorectal cancer., Implications: In the absence of clinical stage data, access to pathology records by population-based cancer registries enables a more accurate assessment of survival inequalities in colorectal cancer survival.

Objective: The difficulties and concerns of colorectal cancer patients with an ostomy are not well documented. This study describes the difficulties experienced by colorectal cancer patients with a temporary or permanent ostomy over the 2-year period following their diagnosis. Patients' satisfaction with the information provided to them by their healthcare providers was also assessed., Methods: Colorectal cancer patients with an ostomy (N 5332) recruited through a cancer registry completed telephone interviews at approximately 5, 12, and 24 months following diagnosis., Results: Painful or irritated peristomal skin and odor and noise from the appliance were the most commonly reported stoma-related difficulties. The proportion of participants reporting these difficulties decreased over time. Provision of preoperative information was comprehensive, and satisfaction with preoperative information was high. However, 34% of patients said they were not seen by an ostomy nurse prior to surgery., Conclusions: The ostomy nurse may be ideally placed to initiate, develop, and implement survivorship care plans for colorectal cancer patients.

Objective: Self-report is commonly used in epidemiologic studies; however, few data exist on the reliability and validity of this method for eliciting information related to the diagnosis of colorectal cancer. We examined the test-retest reliability and validity of colorectal cancer patients reporting on the process of their diagnosis., Study Design and Setting: One hundred and sixteen participants completed two telephone interviews, 1 month apart, and 95 general practitioners (GPs) completed a written questionnaire, to elicit information relating to key elements of the process of diagnosis of colorectal cancer., Results: Acute symptoms such as rectal bleeding had higher reliability and validity than more general symptoms. Colonoscopy was the most accurately recalled diagnostic test. Recall of diagnosis date, and date of colonoscopy, had high test-retest reliability. There were considerable differences between dates of diagnostic tests given by participants and GPs, but there was no evidence of a bias in a particular direction. Accuracy of recall did not diminish as time from diagnosis increased., Conclusion: This study confirms that self-reported symptoms, tests, and dates in the colorectal cancer diagnostic pathway are generally reliable; however, the validity of reported symptoms and tests can be moderate to poor.

Background: Psychological distress in cancer survivors can be detrimental to treatment adherence and self-care tasks and is associated with poor health behaviors and decreased overall quality of life. The prevalence, course, and predictors of psychological distress after the diagnosis of colorectal cancer are to date not well described., Methods: A prospective survey of 1822 colorectal cancer patients was undertaken assessing psychological distress and hypothesized predictors including optimism, cancer threat appraisal, social support, and physical activity at 6 and 12 months postdiagnosis. Logistic regression identified correlates of psychological distress at 12 months postdiagnosis., Results: The prevalence of global psychological distress was low: 8.3% and 6.7% at 6 and 12 months postdiagnosis, respectively. When baseline measures of independent variables were included in a logistic regression model, distress at 6 months postdiagnosis (odds ratio [OR]=10.84), comorbidities (OR=1.64), optimism (OR=0.93), cancer threat appraisal (OR=0.92), and social support (OR=0.94) were significantly associated with distress at 12 months postdiagnosis. A second logistic regression model that included concurrent measures of cancer threat appraisal, social support, and physical activity found that distress at 6 months postdiagnosis (OR=12.49), comorbidities (OR=1.64), optimism (OR=0.94), and concurrent cancer threat appraisal (OR=0.85) were significantly associated with distress at 12 months postdiagnosis., Conclusions: Distress screening at regular intervals is needed to efficiently detect colorectal cancer patients who require in-depth psychological intervention. Threat appraisal is a modifiable variable that should be included in interventions for colorectal cancer survivors. Further research is needed to investigate the potential for physical activity to reduce distress after cancer., (Copyright (c) 2008 American Cancer Society.)

Background: Physical activity can provide benefits to cancer survivors, including reduced symptoms and treatment side effects, improved overall quality of life, and decreased risk of other chronic diseases., Purpose: The aim of the study was to describe physical activity before and after diagnosis of colorectal cancer and to examine the associations with sociodemographic and disease-related variables., Methods: Telephone interviews were conducted with 1,996 colorectal cancer survivors recruited through a cancer registry., Results: In comparison to prediagnosis activity levels, there were 21% fewer participants meeting the physical activity and health guideline (150 min of moderate-intensity physical activity per week) postdiagnosis. Meeting the guideline postdiagnosis was associated with being male, living outside of the state capital city, having a higher education, having a healthy body mass index, not smoking, having had surgery only, and no reported fatigue. Attributes associated with a decrease in physical activity following diagnosis were being female, living within the state capital city, having a lower level of education, having a stoma, having adjuvant therapy, and experiencing fatigue., Conclusions: There is considerable scope for targeted interventions to increase the physical activity of colorectal cancer survivors, particularly for those groups that we have identified as being less active and/or have reduced their activity.

Objective: To examine the associations between physical activity and quality of life for colorectal cancer survivors; and to describe the associations of medical and sociodemographic attributes with overall quality of life, and their moderating effects on the relationships between physical activity and quality of life., Methods: Telephone interviews were conducted with 1,996 colorectal cancer survivors recruited through the Queensland Cancer Registry. Data were collected on current quality of life; leisure-time physical activity pre- and post-diagnosis; cancer treatment and side-effects; and general sociodemographic attributes. Hierarchical generalized linear models identified variables significantly associated with quality of life., Results: After controlling for sociodemographic variables, disease-specific variables, treatment side-effects, and pre-diagnosis leisure-time physical activity, there were significant differences in quality of life scores by post-diagnosis physical activity category. Compared to participants who were inactive after their diagnosis, those who were sufficiently active had a 17.0% higher total quality of life score. Physical activity also had a significant independent positive association with the physical well-being, functional well-being, and additional concerns subscales of the FACT-C., Conclusions: Our findings demonstrate that quite modest changes in leisure-time physical activity are associated with quality of life. Colorectal cancer survivors may benefit from a more active lifestyle.

Objective: To describe the process of colorectal cancer diagnosis in Queensland, and to determine factors associated with time to diagnosis., Design, Setting and Participants: Cross-sectional study of 1996 patients with colorectal cancer recruited through the Queensland Cancer Registry. Data were collected by computer-assisted telephone interview between May 2003 and August 2005., Main Outcome Measures: Time to diagnosis: pre-presentation time (time from first noticing a symptom to first presenting to a doctor); and post-presentation time (time between the first presentation and diagnosis)., Results: Most patients (90%) had experienced symptoms before being diagnosed with colorectal cancer; only 2% of patients were diagnosed by faecal occult blood testing. Older participants and those who experienced abdominal pain had the shortest time from symptom onset to their first doctor consultation, while participants with a change in bowel habit, or rectal bleeding, and those without private health insurance tended to wait longer to see a doctor. Participants who experienced abdominal pain were diagnosed more quickly, whereas those who experienced a change in bowel habit, women, and those without private health insurance experienced a longer time to diagnosis., Conclusions: The strong association between not having health insurance and longer post-presentation times is concerning. The other hypothesised predictors of time to diagnosis were not as strongly associated as we anticipated.

Purpose: This study was conducted to examine the test-retest reliability of a measure of prediagnosis physical activity participation administered to colorectal cancer survivors recruited from a population-based state cancer registry., Methods: A total of 112 participants completed two telephone interviews, 1 month apart, reporting usual weekly physical activity in the year before their cancer diagnosis. Intraclass correlation coefficients (ICC) and standard error of measurement (SEM) were used to describe the test-retest reliability of the measure across the sample; the Bland-Altman approach was used to describe reliability at the individual level. The test-retest reliability for categorized total physical activity (active, insufficiently active, sedentary) was assessed using the kappa statistic., Results: When the complete sample was considered, the ICC ranged from 0.40 (95% CI: 0.24, 0.55) for vigorous gardening to 0.77 (95% CI: 0.68, 0.84) for moderate physical activity. The SEM, however, were large, indicating high measurement error. The Bland-Altman plots indicated that the reproducibility of data decreases as the amount of physical activity reported each week increases. The kappa coefficient for the categorized data was 0.62 (95% CI: 0.48, 0.76)., Conclusion: Overall, the results indicated low levels of repeatability for this measure of historical physical activity. Categorizing participants as active, insufficiently active, or sedentary provides a higher level of test-retest reliability.