| 1. |
- Archambault, Alexi N., et al.
(författare)
-
Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
-
Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
|
|
| 2. |
- de Gonzalez, Amy Berrington, et al.
(författare)
-
Body-Mass Index and Mortality among 1.46 Million White Adults.
- 2010
-
Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 363:23, s. 2211-2219
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. Methods: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). Results: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. Conclusions: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9. N Engl J Med 2010;363:2211-9.
|
|
| 3. |
- Jayasekara, Harindra, et al.
(författare)
-
Alcohol consumption for different periods in life, intake pattern over time and all-cause mortality
- 2015
-
Ingår i: Journal of Public Health. - : Oxford University Press (OUP). - 1741-3842 .- 1741-3850. ; 37:4, s. 625-633
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Conventionally, cohort studies have assessed the association between alcohol and all-cause mortality by using alcohol intake at enrolment.Methods: In theMelbourne Collaborative Cohort Study, participants were asked about usual frequency and quantity of beverage-specific alcoholintake for 10-year periods starting at age 20 from which current, past and lifetime intakes were calculated.We used Cox regression to estimate hazardratios for mortality for 39 577 participants of theMelbourne Collaborative Cohort Study aged 40–69 at baseline.Results: After a mean follow-up of 15 years/person, we identified 4639 deaths. Associations between all-cause mortality and lifetime, current(baseline) and past intakewere J shaped, with lower mortality at low intake (e.g. ,40 g/day for men and 10 g/day for women using lifetime intake)and elevated mortality at higher intake. Formen, consistent light-to-moderate drinking (.0–39/.0–39 g/day) from age 20 to baseline agewasassociated with a 16% lower mortality, while heavy drinking at both ages (80/40 and 40/0 g/day) was associated with higher mortality comparedwith stable abstinence.Conclusions: Our findings support a reduced mortality risk associated with low-dose drinking but also highlight a higher mortality risk for consistentheavy drinking from a young age.
|
|
| 4. |
- Jayasekara, Harindra, et al.
(författare)
-
Alcohol Consumption Over Time and Risk of Death : A Systematic Review and Meta-Analysis
- 2014
-
Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 179:9, s. 1049-1059
-
Forskningsöversikt (refereegranskat)abstract
- The results from the few cohort studies that have measured usual alcohol consumption over time have not been summarized. We therefore conducted a systematic review and meta-analysis to quantify mortality risk. Pertinent studies were identified by searching the Medline, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Scopus databases through August 2012 using broad search criteria. Studies reporting relative mortality risks for quantitatively defined categories of alcohol consumption over time were eligible. Nine cohort studies published during 1991-2010 (comprising 62,950 participants and 10,490 deaths) met the inclusion criteria. For men, there was weak evidence of lower mortality risk with low levels of alcohol intake over time but higher mortality risk for those with intakes over 40 g/day compared with abstainers using a random-effects model (P for nonlinearity = 0.02). The pooled relative risks were 0.90 (95% confidence interval: 0.81, 0.99) for 1-29 g/day, 1.19 (95% confidence interval: 0.89, 1.58) for 30-59 g/day, and 1.52 (95% confidence interval: 0.78, 2.98) for 60 or more g/day compared with abstention. There was moderate between-study heterogeneity but no evidence of publication bias. Studies including women were extremely scarce. Our findings include a curvilinear association between drinking over time and mortality risk for men overall and widespread disparity in methods used to capture exposure and report results.
|
|
| 5. |
- Jayasekara, Harindra, et al.
(författare)
-
Associations of alcohol intake, smoking, physical activity and obesity with survival following colorectal cancer diagnosis by stage, anatomic site and tumor molecular subtype
- 2018
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:2, s. 238-250
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 6. |
- Jayasekara, Harindra, et al.
(författare)
-
Is breast cancer risk associated with alcohol intake before first full-term pregnancy?
- 2016
-
Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 27:9, s. 1167-1174
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeIt is plausible that breast tissue is particularly susceptible to carcinogens, including ethanol, between menarche and the first full-term pregnancy (first pregnancy). There is some epidemiological evidence that intake before the first pregnancy is more closely associated with risk of breast cancer than is intake thereafter. We examined this association using lifetime alcohol consumption data from a prospective cohort study.MethodsWe calculated usual alcohol intake for age periods 15-19 years and for 10-year period from age 20 to current age (in grams per day) using recalled frequency and quantity of beverage-specific consumption for 13,630 parous women who had their first pregnancy at age 20 years or later, had no cancer history and were aged 40-69 years at enrollment. Cox regression was performed to estimate hazard ratios (HRs) and their 95 % confidence intervals (CIs).ResultsA total of 651 incident invasive adenocarcinomas of the breast were diagnosed during a mean follow-up of 16.1 years. Alcohol consumption was low overall with only a few drinking >= 40 g/day. Intake before the first pregnancy was markedly lower (mean intake: 2.5 g/day; abstention: 58.8 %) than intake thereafter (mean intake: 6.0 g/day; abstention: 33.6 %). Any alcohol intake before the first pregnancy was associated with an increased risk of breast cancer (HR 1.35, 95 % CI 1.10-1.66 for drinking compared with abstention), whereas any intake after the first pregnancy was not (HR 0.89, 95 % CI 0.72-1.09).ConclusionsLimiting alcohol intake before the first pregnancy might reduce women's risk of breast cancer.
|
|
| 7. |
- Jayasekara, Harindra, et al.
(författare)
-
Lifetime alcohol consumption and upper aero-digestive tract cancer risk in the Melbourne Collaborative Cohort Study
- 2015
-
Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 26:2, s. 297-301
-
Tidskriftsartikel (refereegranskat)abstract
- Cohort studies have rarely examined the association between upper aero-digestive tract (UADT) cancer risk and lifetime alcohol intake. We examined the associations between incident squamous cell carcinoma of the UADT (oral cavity, pharynx, larynx, and esophagus) and alcohol intake for different periods in life using data from the Melbourne Collaborative Cohort Study. Usual alcohol intake for 10-year periods from age 20 was calculated using recalled frequency and quantity of beverage-specific consumption. Cox regression with age as the time axis was performed to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the associations of UADT cancer with alcohol intake for different periods in life compared with abstention. During a mean follow-up of 16.2 person-years, 98 incident cases of UADT cancer were identified. We observed a dose-dependent association between lifetime alcohol intake and the risk of UADT cancer (multivariable-adjusted HR 2.67, 95 % CI 1.27-5.60 for an intake of a parts per thousand yen40 g/day and multivariable-adjusted HR 1.16, 95 % CI 1.06-1.28 for a 10 g/day increment in intake). A positive association with baseline alcohol intake (multivariable-adjusted HR 1.12, 95 % CI 1.02-1.24 for a 10 g/day increment in intake) was found to be a slightly weaker predictor of risk than lifetime intake. Limiting alcohol intake from early adulthood may reduce UADT cancer risk.
|
|
| 8. |
- Jayasekara, Harindra, et al.
(författare)
-
Lifetime alcohol intake and pancreatic cancer incidence and survival : findings from the Melbourne Collaborative Cohort Study
- 2019
-
Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 30:4, s. 323-331
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Pancreatic cancer has one of the worst prognoses with 5-year survival below 10%. There is some evidence that alcohol consumption might increase the risk of pancreatic cancer. We examined associations of pre-diagnostic alcohol intake with (i) incidence of pancreatic cancer, and (ii) overall survival following pancreatic cancer. Methods Usual alcohol intake was estimated at recruitment in 1990-1994 for 38,472 participants in the Melbourne Collaborative Cohort Study using recalled frequency and quantity of beverage-specific intake for 10-year periods from age 20. Pancreatic cancer incidence (C25 according to International Classification of Diseases for Oncology) and vital status were ascertained through to 30 September 2015. Cox regression was performed to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with lifetime, age 20-29, and baseline alcohol intakes. Results By the end of follow-up (average 20.2 years), 239 incident cases of pancreatic cancer were diagnosed, of which 228 had died. No evidence of an association was observed between alcohol intake and risk of pancreatic cancer. Higher lifetime alcohol intake was associated with lower overall survival following a diagnosis of pancreatic cancer (mortality HR 1.09 per 10 g/day increment, 95% CI 1.00-1.19; p value=0.04). A similar finding was observed for age 20-29 intake (HR 1.09 per 10 g/day increment, 95% CI 1.02-1.18; p value=0.01) but not with baseline intake. Conclusions We observed an association between lower alcohol use from an early age and improved survival following pancreatic cancer, but this finding needs to be confirmed by other studies.
|
|
| 9. |
- Jayasekara, Harindra, et al.
(författare)
-
Lifetime alcohol intake and risk of non-Hodgkin lymphoma : Findings from the Melbourne Collaborative Cohort Study
- 2018
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:5, s. 919-926
-
Tidskriftsartikel (refereegranskat)abstract
- Cohort studies have reported inconsistent evidence regarding alcohol intake and risk of non-Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close to study enrolment. We examined this association using alcohol intake measured from age 20 onwards. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 37,990 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 alcohol intake (g/day) and NHL risk. After a mean follow-up of 19.3 years, 538 NHL cases were diagnosed. Approximately 80% of participants were either lifetime abstainers or consumed below 20 g of ethanol/day. All categories of lifetime alcohol intake were associated with about 20% lower incidence of NHL compared with lifetime abstention, but there was no evidence of a trend by amount consumed (HR=0.97 per 10 g/day increment in intake, 95% CI: 0.92-1.03; p value=0.3). HRs for beer, wine and spirits were 0.91 (95% CI: 0.83-1.00; p value=0.05), 1.03 (95% CI: 0.94-1.12; p value=0.6), and 1.06 (95% CI: 0.83-1.37; p value=0.6), respectively, per 10 g/day increment in lifetime intake. There were no significant differences in associations between NHL subtypes. In this low-drinking cohort, we did not detect a dose-dependent association between lifetime alcohol intake and NHL risk.
|
|
| 10. |
- Jayasekara, Harindra, et al.
(författare)
-
Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer : A pooled analysis of data from two prospective cohort studies
- 2021
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 148:11, s. 2759-2773
-
Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity =.02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
|
|
