Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.

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) ß, 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.

Which cancer survivors are at risk for a physically inactive and sedentary lifestyle? Results from pooled accelerometer data of 1447 cancer survivors.

BACKGROUND: Physical activity has beneficial effects on the health of cancer survivors. We aimed to investigate accelerometer-assessed physical activity and sedentary time in cancer survivors, and describe activity profiles. Additionally, we identify demographic and clinical correlates of physical activity, sedentary time and activity profiles. METHODS: Accelerometer, questionnaire and clinical data from eight studies conducted in four countries (n = 1447) were pooled. We calculated sedentary time and time spent in physical activity at various intensities using Freedson cut-points. We used latent profile analysis to identify activity profiles, and multilevel linear regression analyses to identify demographic and clinical variables associated with accelerometer-assessed moderate to vigorous physical activity (MVPA), sedentary time, the highly active and highly sedentary profile, adjusting for confounders identified using a directed acyclic graph. RESULTS: Participants spent on average 26 min (3%) in MVPA and 568 min (66%) sedentary per day. We identified six activity profiles. Older participants, smokers and participants with obesity had significantly lower MVPA and higher sedentary time. Furthermore, men had significantly higher MVPA and sedentary time than women and participants who reported less fatigue had higher MVPA time. The highly active profile included survivors with high education level and normal body mass index. Haematological cancer survivors were less likely to have a highly active profile compared to breast cancer survivors. The highly sedentary profile included older participants, males, participants who were not married, obese, smokers, and those < 12 months after diagnosis. CONCLUSIONS: Cancer survivors engage in few minutes of MVPA and spend a large proportion of their day sedentary. Correlates of MVPA, sedentary time and activity profiles can be used to identify cancer survivors at risk for a sedentary and inactive lifestyle.

Predictors of physical activity in colorectal cancer survivors after participation in a telephone-delivered multiple health behavior change intervention.

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.

Objectively assessed physical activity, sedentary time and waist circumference among prostate cancer survivors: findings from the National Health and Nutrition Examination Survey (2003-2006).

Physical activity is well-established on the cancer survivorship research agenda, but prostate cancer survivors remain an understudied population. Additionally, the unique relationships between sedentary time and health outcomes have not yet been considered in this group. We examined the associations of accelerometer-assessed physical activity and sedentary time with waist circumference in 103 prostate cancer survivors from the National Health and Nutrition Examination Survey 2003-2004 and 2005-2006. Participants wore an Actigraph accelerometer for 7 days, and activity levels were summarised as moderate-to-vigorous intensity activity (accelerometer counts/minute ≥ 1952), light-intensity activity (counts/minute 100-1951) and sedentary time (counts/minute < 100). Moderate-to-vigorous intensity physical activity was inversely associated with waist circumference (ß=-6.728, 95% CI: -12.267, -1.190, P= 0.020), equating to a top versus bottom quartile difference of 13.7 cm. No discernable relationship existed between light-intensity activity or sedentary time and adiposity. This is the first study to objectively measure the activity levels of prostate cancer survivors. Increasing moderate-to-vigorous activity may assist this population with weight management. More research into the relationships of light-intensity physical activity and sedentary behaviour with health outcomes among prostate cancer survivors is warranted, given the strong relationships seen in the broader population.

Scoreboard advertising at sporting events as a health promotion medium.

This report describes spectator recall of SunSmart skin cancer prevention advertising displayed on the Brisbane Cricket Ground scoreboard at intermittent periods throughout the 1999/2000 cricket season and the sun-protective behaviors of these spectators. Two hundred and thirty-one spectators were asked a series of five questions about their recall of SunSmart advertising and their present sunscreen usage. Respondents' sun-protective behavior observed at the time of questioning was also recorded. The SunSmart advertising was seen by 15.6% of respondents. Recall of the SunSmart advertising was higher amongst spectators observed to have high levels of sun protection than amongst spectators with low levels of sun protection. Females were more likely than males to recall the SunSmart advertising. The efficacy of health-promoting advertising in the sports setting has yet to be established and therefore results cannot be compared against accepted benchmarks. This study contributes baseline data that will enable such comparisons to be made. The increase in recent years of health-promoting advertising at sports events, often as part of a comprehensive sponsorship program, necessitates the need for further research in this area.