Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- but not BRAF+ colorectal cancer.

Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 38,149 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose-dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow-up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04-1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (phomogeneity  = 0.02). Alcohol intake was associated with increased risks of KRAS+ (HR = 1.07, 95% CI: 1.00-1.15) and BRAF-/KRAS- (HR = 1.05, 95% CI: 1.00-1.11) but not BRAF+ tumors (HR = 0.89, 95% CI: 0.78-1.01; phomogeneity  = 0.01). Alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- tumors originating via specific molecular pathways including the traditional adenoma-carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma-carcinoma pathway

Associations of alcohol intake, smoking, physical activity and obesity with survival following colorectal cancer diagnosis by stage, anatomic site and tumor molecular subtype.

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

A prospective study of lifetime alcohol consumption and the risk of breast, upper aero-digestive tract and colorectal cancer, and mortality

© 2014 Dr. Harindra Dilantha Madawala Hubert JayasekaraAlcohol consumption is a major risk factor for preventable chronic disease and injury worldwide while ethanol in alcohol is a carcinogen. On the other hand, moderate drinking has an apparent beneficial effect on cardiovascular health and is associated with lower mortality while heavy drinking is associated with higher mortality than abstinence. The evidence comes mainly from epidemiological studies which have measured alcohol consumption close to study enrolment (‘current’ drinking). Intake over a prolonged period of time is likely to correlate more closely with chronic outcomes. Using data from a prospective cohort study of 41,514 people predominantly aged 40-69 years at recruitment in 1990-94, the associations of alcohol consumption for different periods in life (i.e. lifetime, baseline and past) with the risk of mortality, and breast, upper aero-digestive tract and colorectal cancer incidence were assessed. Alcohol consumption was assessed at study enrolment retrospectively for 10-year age periods from age 20 onwards. The participants were followed-up for approximately 15 years. Deaths were identified through national death indices and incident cases of cancer were ascertained via the population cancer registry. Cox regression with age as the time metric was performed to estimate hazard ratios and 95% confidence intervals for the associations of alcohol consumption with mortality and cancer. A curvilinear dose-response relationship between all-cause mortality and alcohol consumption irrespective of the period of intake was observed with lower mortality at low levels of intake compared with abstention. An increased mortality risk at higher levels of intake was evident for men. Consistent moderate drinking between age 20-29 and current age was also associated with lower mortality for men while consistent heavy drinking over time was associated with higher mortality, compared with consistent abstention. For men, the model using lifetime intake gave a better fit to the data than the model using baseline intake while both models gave similar fits for women. Incidence of breast cancer showed a weak dose-dependent association with lifetime alcohol intake while breast cancer risk did not increase with increasing baseline alcohol consumption. A dose-dependent association between lifetime alcohol intake and upper aero-digestive tract cancer incidence was observed while baseline intake was also positively associated with the incidence of upper aero-digestive tract cancer. Lifetime intake gave a slightly better fit to the data than baseline intake. A positive association between lifetime alcohol intake and colorectal cancer incidence was observed. A higher risk of colorectal cancer with greater alcohol consumption between age 20-29 and baseline that was more prominent for men was also observed. Past intake for age 20-29 for men and lifetime intake for women gave the best fits to the data. In conclusion, moderate lifetime alcohol consumption was associated with lower mortality and heavy drinking from young adulthood to middle-age with higher mortality. Lifetime alcohol intake showed a positive association with breast, upper aero-digestive tract and colorectal cancer incidence. The period of exposure relevant to alcohol as a risk factor for mortality and incidence of breast, upper aero-digestive tract and colorectal cancer extends beyond ‘current’ age. Limiting intake from a young age may reduce the incidence of these cancers. Advice to limit the usual volume of drinking from young adulthood to middle-age should be based on age, risk factors for the particular cancer and cardiovascular disease, and preceding and current alcohol consumption

Drinking cultures and social occasions: alcohol harms in the context of major sporting events

This report looks at the harms associated with alcohol consumption in the context of major sporting events which were explored in terms of general patterns, gender and age patterns. A range of alcohol-related harms were considered, including acute intoxication requiring medical attention, assaults, and motor vehicle accidents. The use of time series analysis allows exploration of the levels of harms associated with specific events after controlling for the impact of seasonal and temporal variations in alcohol-related harms. Across all populations examined, the peak months of the year for ambulance attendances, emergency department presentations, and hospital admissions attributed to acute alcohol intoxication were November and December, with February also being identified as a peak month among males. Consistent with the literature, Fridays and Saturdays were the days with the highest concentrations of alcohol intoxication related attendances, presentations and admissions. Varying effects were noted for major sporting events. Significantly elevated numbers of cases of acute alcohol intoxication were evident for all groups examined on the day before the Melbourne Cup, whilst elevated cases were seen for all patients and for males on the day before the AFL Grand Final. For all groups examined, elevated cases of alcohol intoxication occurred on the day of the Melbourne Cup, and also for all groups except females on the day of the AFL Grand Final and the event of the Commonwealth Games. Numbers of ambulance attendances for acute intoxication were significantly lower than expected on the day following the Melbourne Cup for all patients, and this was driven by the trend among females. Image: ra_hurd / flick

Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross-sectional and longitudinal data

International audienceDNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart. Using the Illumina HumanMethylation450 BeadChip, DNA methylation was measured in blood samples from 5606 Melbourne Collaborative Cohort Study (MCCS) participants. For 1088 of them, these measures were repeated using blood samples collected a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models. Independent data from the London Life Sciences Prospective Population (LOLIPOP) (N = 4042) and Cooperative Health Research in the Augsburg Region (KORA) (N = 1662) cohorts were used to replicate associations discovered in the MCCS. Cross-sectional analyses identified 1414 CpGs associated with alcohol intake at P < 10−7, 1243 of which had not been reported previously. Of these novel associations, 1078 were replicated (P <.05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated 403 of 518 previously reported associations. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1414 CpGs, 530 were differentially methylated (P <.05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1414 cross-sectional associations. Our study indicates that alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with alcohol consumption changes in adulthood