| 1. |
- Drake, Isabel, et al.
(författare)
-
Lifestyle and cancer incidence and mortality risk depending on family history of cancer in two prospective cohorts
- 2020
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:5, s. 1198-1207
-
Tidskriftsartikel (refereegranskat)abstract
- The extent to which a favorable lifestyle may lower cancer risk in subjects with a family history of cancer is unknown. We conducted a prospective study in two Swedish cohorts, the Malmö Diet and Cancer Study (MDCS; n = 25,604) and the Malmö Preventive Project (MPP; n = 16,216). The association between a favorable lifestyle (based on nonsmoking, normal weight, absence of excessive drinking, regular physical activity and healthy diet) and cancer incidence and mortality risk was assessed using Cox regression stratified by family history of cancer (all types). A favorable lifestyle was associated with a 22% (95% confidence interval [CI]: 18–26%) and 40% (95% CI: 36–44%) lower risk of cancer incidence and mortality, respectively, compared to an unfavorable lifestyle. No significant effect modification by family history was observed but there was a null association between lifestyle and cancer incidence among subjects with two or more affected first-degree relatives. The observed relative risk estimates comparing an unfavorable with a favorable lifestyle corresponded to standardized 10-year cancer incidence rates of 11.2 vs. 9.5% in the MDCS, and 4.4 vs. 3.2% in the MPP, and a reduction in 20-year cancer mortality rate from 11.7% to 7.4% in the MDCS and 6.7% to 3.9% in the MPP. Improved adherence to cancer prevention recommendations may reduce cancer incidence and mortality risk in the general population, however, further studies are needed to assess the impact of lifestyle on cancer incidence among subjects with strong familial or polygenic risk for specific cancers.
|
|
| 2. |
- Fritz, Josef, et al.
(författare)
-
The triglyceride-glucose index as a measure of insulin resistance and risk of obesity-related cancers
- 2020
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 49:1, s. 193-204
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified.METHODS: Altogether 510 471 individuals from six European cohorts, with a mean age of 43.1 years, were included. We used the triglyceride glucose product (TyG index) as a surrogate measure for insulin resistance. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with 10 common obesity-related cancers, and quantified the proportion of the effect of BMI mediated through TyG index on the log-transformed hazard ratio (HR) scale.RESULTS: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney HR per one standard deviation increase 1.13, 95% confidence interval: 1.07 to 1.20], liver (1.13, 1.04 to 1.23), pancreas (1.12, 1.06 to 1.19), colon (1.07, 1.03 to 1.10) and rectum (1.09, 1.04 to 1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%) and colon (20%); smaller proportions for kidney (15%) and liver (11%). Little or no mediation was observed for breast (postmenopausal), endometrial and ovarian cancer. Results were similar for males and females, except for pancreatic cancer where the proportions mediated were 20% and 91%, respectively.CONCLUSIONS: The TyG index was associated with increased risk of cancers of the digestive system and substantially mediated the effect of BMI, suggesting that insulin resistance plays a promoting role in the pathogenesis of gastrointestinal cancers.
|
|
| 3. |
- Mutie, Pascal M., et al.
(författare)
-
Different domains of self-reported physical activity and risk of type 2 diabetes in a population-based Swedish cohort : the Malmö diet and Cancer study
- 2020
-
Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: While a dose-response relationship between physical activity and risk of diabetes has been demonstrated, few studies have assessed the relative importance of different measures of physical activity on diabetes risk. The aim was to examine the association between different self-reported measures of physical activity and risk of type 2 diabetes in a prospective cohort study. METHODS: Out of 26,615 adults (45-74 years, 60% women) in the population-based Swedish Malmö Diet and Cancer Study cohort, 3791 type 2 diabetes cases were identified from registers during 17 years of follow-up. Leisure-time (17 activities), occupational and domestic physical activity were assessed through a questionnaire, and these and total physical activity were investigated in relation to type 2 diabetes risk. RESULTS: All physical activity measures showed weak to modest associations with type 2 diabetes risk. The strongest association was found in the lower end of leisure-time physical activity in dose-response analysis at levels approximately below 22 MET-hrs/week (300 min/week) representing around 40% of the population. Compared with the lowest quintile, the moderate leisure-time physical activity category had a 28% (95% CI: 0.71, 0.87) decreased risk of type 2 diabetes. Total physical activity showed a similar, but weaker, association with diabetes risk as to that of leisure-time physical activity. Domestic physical activity was positively and linearly related to diabetes risk, HR = 1.11 (95% CI: 0.99, 1.25) comparing highest to lowest quintile. There was no association between occupational physical activity and diabetes risk. CONCLUSION: A curvilinear association was observed between leisure-time physical activity and risk of diabetes. Beyond a threshold level of approximately 22 MET-hrs/week or 300 min/week, no additional risk reduction was observed with increase in physical activity.
|
|
| 4. |
- Nagel, Gabriele, et al.
(författare)
-
Metabolic factors and the risk of small intestine cancers : pooled study of 800 000 individuals in the Metabolic syndrome and Cancer project
- 2021
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 149:1, s. 66-74
-
Tidskriftsartikel (refereegranskat)abstract
- To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Amongst 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HR) of small intestine cancer by levels of BMI, mean arterial pressure (MAP), and plasma total cholesterol, triglycerides and glucose. We also calculated HRs for these factors combined (metabolic score; MetS) and used Wald test statistics to investigate pairwise interactions between metabolic factors on risk. We also performed analyses separately per subtype (neuroendocrine tumors (NETs) and adenocarcinomas). During a median follow-up of 16.9 years, 144 women and 195 men were diagnosed with small intestine cancer, including 184 NETs and 99 adenocarcinomas. Among men, no main associations or interactions between metabolic factors were observed in relation to the risk of small intestine cancer. Among women, triglycerides were positively and linearly associated with risk (HR per standard deviation [SD]: 1.23, 95% CI 1.04 to 1.46), and a positive association was also observed for the MetS (HR per SD: 1.25, 95% CI 1.02 to 1.52). Positive interactions were observed among women between triglycerides and cholesterol (p=0.0005), and between MAP and glucose (p=0.009), on risk. Glucose was positively associated with adenocarcinomas among women. This large, prospective study suggests that elevated triglycerides, and metabolic factors in interaction, confer an increased risk of small intestine cancer among women, but not among men.
|
|
| 5. |
- Sun, Ming, et al.
(författare)
-
Interaction of leisure-time physical activity with body mass index on the risk of obesity-related cancers : A pooled study
- 2022
-
Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:6, s. 859-868
-
Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) has been associated with a lower risk of some obesity-related cancers, but the combined association and interaction of PA and body weight on obesity-related cancer risk is less clear. We examined the association of leisure-time PA (high/low) and its combination with body mass index (BMI, <25 [low]/≥25 [high] kg/m2) on obesity-related cancer risk in 570 021 individuals, aged 43 years on average at baseline, in five Scandinavian cohorts. We used Cox regression to calculate hazard ratios of obesity-related cancers (n = 19 074) and assessed multiplicative and additive interactions between PA and BMI on risk. High leisure-time PA, recorded in 19% of the individuals, was associated with a 7% (95% confidence interval [CI] 4%-10%) lower risk of any obesity-related cancer compared to low PA, with similar associations amongst individuals with a low and a high BMI (6% [1%-11%] and 7% [2%-11%]). High PA was also associated with decreased risks of renal cell (11% [9%-31%]) and colon cancer (9% [2%-16%]). When high PA and low BMI were combined, the relative risk reduction for all obesity-related cancers was 24% (95% CI 20%-28%); endometrial cancer, 47% (35%-57%); renal cell cancer, 39% (27%-51%); colon cancer, 27% (19%-35%); multiple myeloma, 23% (2%-40%) and pancreatic cancer, 21% (4%-35%), compared to low PA-high BMI. There were no additive or multiplicative interactions between PA and BMI on risk. The result of our study suggests a reduced risk of obesity-related cancer by leisure-time PA in both normal weight and overweight individuals, which further decreased for PA and normal weight combined.
|
|
| 6. |
- Teleka, Stanley, et al.
(författare)
-
Association between blood pressure and BMI with bladder cancer risk and mortality in 340,000 men in three Swedish cohorts
- 2021
-
Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 10:4, s. 1431-1438
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The relation between obesity, blood pressure (BP) and bladder cancer (BC) risk and mortality remains unclear, partially due to potential confounding by smoking, the strongest risk factor for BC, and not accounting for tumor stage and grade in such studies. We investigated body mass index (BMI) and BP in relation to BC risk by stage and grade, and BC-specific mortality, including separately among never-smokers aimed at minimizing confounding by smoking. Methods: We analyzed 338,910 men from three Swedish cohorts, with 4895 incident BC's (940 among never-smokers) during follow-up. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals adjusted for smoking status. HRs for BMI and BP were corrected for their regression dilution ratios, calculated from 280,456 individuals with 758,641 observations. Results: Body mass index was positively associated with non-muscle invasive BC (NMIBC, HR per 5 kg/m2, 1.10 [1.02–1.19]) and NMIBC grade 3 (HR 1.17 [1.01–1.34]) in the full cohort, with similar effect sizes, albeit non-significant, among never-smokers. Systolic BP was positively associated with muscle-invasive BC (MIBC, HR per 10 mmHg, 1.25 [1.00–1.55]) and BC-specific mortality (HR 1.10 [1.01–1.20]) among never-smokers, with weaker and non-significant associations in the full cohort. Conclusions: In an analyses of BMI, BP and BC risk by stage and grade among men, we found modest positive associations between BMI and NMIBC and NMIBC grade 3. SBP was positively associated with MIBC and BC-specific mortality in an analysis of never-smokers, which may reflect the association, un-confounded by smoking, also in a broader population.
|
|
| 7. |
- Teleka, Stanley, et al.
(författare)
-
Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis
- 2020
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11 November
-
Tidskriftsartikel (refereegranskat)abstract
- The association between blood pressure (BP) and bladder cancer (BC) risk remains unclear with confounding by smoking being of particular concern. We investigated the association between BP and BC risk among men using conventional survival-analysis, and by Mendelian Randomization (MR) analysis in an attempt to disconnect the association from smoking. We additionally investigated the interaction between BP and N-acetyltransferase-2 (NAT2) rs1495741, an established BC genetic risk variant, in the association. Populations consisting of 188,167 men with 502 incident BC's in the UK-biobank and 27,107 men with 928 incident BC's in two Swedish cohorts were used for the analysis. We found a positive association between systolic BP and BC risk in Cox-regression survival analysis in the Swedish cohorts, (hazard ratio [HR] per standard deviation [SD]: 1.14 [95% confidence interval 1.05-1.22]) and MR analysis (odds ratio per SD: 2-stage least-square regression, 7.70 [1.92-30.9]; inverse-variance weighted estimate, 3.43 [1.12-10.5]), and no associations in the UK-biobank (HR systolic BP: 0.93 [0.85-1.02]; MR OR: 1.24 [0.35-4.40] and 1.37 [0.43-4.37], respectively). BP levels were positively associated with muscle-invasive BC (MIBC) (HRs: Systolic BP, 1.32 [1.09-1.59]; diastolic BP, 1.27 [1.04-1.55]), but not with non-muscle invasive BC, which could be analyzed in the Swedish cohorts only. There was no interaction between BP and NAT2 in relation to BC on the additive or multiplicative scale. These results suggest that BP might be related to BC, more particularly MIBC. There was no evidence to support interaction between BP and NAT2 in relation to BC in our study.
|
|
| 8. |
- Teleka, Stanley, et al.
(författare)
-
Interaction between blood pressure and genetic risk score for bladder cancer, and risk of urothelial carcinoma in men.
- 2022
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1, s. 18336-
-
Tidskriftsartikel (refereegranskat)abstract
- There is substantial genetic predisposition to bladder cancer (BC). Recently, blood pressure (BP) was positively associated with BC risk in men, but the potential interaction with genetic susceptibility for BC is unknown. We investigated a weighted genetic risk score (wGRS) of 18 BC genetic variants, BP, and their interaction, in relation to incident urothelial cancer (UC, n = 385) risk in 10,576 men. We used Cox regression, the likelihood ratio test, and the relative excess risk for interaction to calculate hazard ratios (HR) of UC, multiplicative interaction and additive interaction respectively. There was evidence of a positive additive interaction between SBP and the wGRS in relation to aggressive (P = 0.02) but not non-aggressive (P = 0.60) UC. The HR of aggressive UC was for SBP ≥ 140 mmHg and the upper 50% of the wGRS combined 1.72 (95% CI 1.03-2.87) compared to the counterpart group. Additionally, the 20-year risk of aggressive UC in 60 year-old men was 0.78% in the low SBP/low wGRS group and 1.33% in the high SBP/high wGRS group. Our findings support a potential additive interaction between the wGRS and SBP on aggressive UC among men. If replicated, the findings on interaction may provide biological and public health insight to prevent aggressive UC.
|
|
| 9. |
- Teleka, Stanley
(författare)
-
Metabolic factors and bladder cancer risk and mortality. Studies to approach causal associations and interactions with smoking and genetic variants.
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Urothelial bladder cancer (BC) is one of the most common cancers in developed countries. It has one of the highest recurrence rates among solid tumors, resulting in regular treatment and follow-up, making it one of the most expensive cancers to treat, and a significant public health burden. Derangement of metabolic factors such as body mass index (BMI), blood pressure (BP), glucose, triglycerides (TG) and cholesterol (TC) has resulted inglobal epidemics such as obesity, hypertension, diabetes and dyslipidemia, which collectively impact cardiovascular disease and certain cancers. Previous studies investigating the link between metabolic factors andBC have shown inconsistent results, furthermore, additive and multiplicative interactions, which may inform biological mechanisms, are rarely investigated in such studies.This thesis aimed to clarify the link between metabolic factors and BC, especially BP, by investigating the association between metabolic factors and BC risk (total, and separately into sub-groups based on tumor characteristics) and BC-specific mortality, using conventional survival analysis and additionally for BP, MendelianRandomization (MR) analysis, and to assess additive and multiplicative interaction with smoking and BC genetic variants in such associations.In studies that spanned several prospective cohorts, we found, as main findings among men: a positive association between systolic BP (SBP) and muscle-invasive BC (MIBC)/aggressive urothelial cancer risk (paper Ⅰ-Ⅳ), and a stronger association among never-smokers, both in conventional survival analysis and MR analysis of a Swedish cohort, a positive association between BMI, TG and TC and non-muscle invasive BC (NMIBC) risk, and a positive association between SBP and TG and risk of BC-specific mortality. Among women (paper Ⅰ), we found aninverse association between BMI and total BC risk, a positive association between glucose and MIBC risk, and a positive association between TG and risk of BC-specific mortality. In the interaction analysis among men, SBP and DBP did not interact with NAT2 in relation to total BC risk; however, SBP and a genetic score for BC positively interacted on an additive scale, in relation to MIBC risk.In conclusion, aberrations in metabolic factors was associated with BC outcomes; the associations differed depending on the sub-group of population and the specific outcome being investigated. Among men, SBP consistently showed a positive association with MIBC risk, furthermore, SBP and the genetic risk of BC positively interacted on an additive scale. The thesis highlights the importance of investigating associations in specific subgroups of the population and specific BC outcomes, and assessing interaction to explore potential biological mechanisms and inform public health.
|
|
| 10. |
- Teleka, Stanley, et al.
(författare)
-
Risk of bladder cancer by disease severity in relation to metabolic factors and smoking : A prospective pooled cohort study of 800,000 men and women
- 2018
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 143:12, s. 3071-3082
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies on metabolic factors and bladder cancer (BC) risk have shown inconsistent results and have commonly not investigated associations separately by sex, smoking, and tumor invasiveness. Among 811,633 participants in six European cohorts, we investigated sex-specific associations between body mass index (BMI), mid-blood pressure (BP, [systolic + diastolic]/2), plasma glucose, triglycerides, total cholesterol and risk of BC overall, non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Among men, we additionally assessed additive interactions between metabolic factors and smoking on BC risk. During follow-up, 2,983 men and 754 women were diagnosed with BC. Among men, triglycerides and BP were positively associated with BC risk overall (hazard ratio [HR] per standard deviation [SD]: 1.17 [95% confidence interval (CI) 1.06–1.27] and 1.09 [1.02–1.17], respectively), and among women, BMI was inversely associated with risk (HR: 0.90 [0.82–0.99]). The associations for BMI and BP differed between men and women (pinteraction ≤ 0.005). Among men, BMI, cholesterol and triglycerides were positively associated with risk for NMIBC (HRs: 1.09 [95% CI 1.01–1.18], 1.14 [1.02–1.25], and 1.30 [1.12–1.48] respectively), and BP was positively associated with MIBC (HR: 1.23 [1.02–1.49]). Among women, glucose was positively associated with MIBC (HR: 1.99 [1.04–3.81]). Apart from cholesterol, HRs for metabolic factors did not significantly differ between MIBC and NMIBC, and there were no interactions between smoking and metabolic factors on BC. Our study supports an involvement of metabolic aberrations in BC risk. Whilst some associations were significant only in certain sub-groups, there were generally no significant differences in associations by smoking or tumor invasiveness.
|
|
| 11. |
- Teleka, Stanley, et al.
(författare)
-
The interaction between smoking and bladder cancer genetic variants on urothelial cancer risk by disease aggressiveness
- 2022
-
Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 11:15, s. 2896-2905
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSmoking has shown interactions with bladder cancer (BC) genetic variants, especially N-acetyltransferase-2 (NAT2), a tobacco smoke metabolism gene, on BC risk. The interactions by disease aggressiveness are unknown.MethodsWe investigated the interaction between smoking and 18 single nucleotide polymorphisms (SNPs) for BC, individually and in a genetic risk score (GRS), on urothelial cancer (UC) risk including BC. We analysed data from 25,453 individuals with 520 incident UCs during follow-up, 339 non-aggressive (non-fatal, non-muscle invasive) and 163 aggressive (all other) UCs. Hazard ratios (HRs), absolute risks and additive and multiplicative interactions for two-by-two combinations of never/ever smoking with low/high genetic risk were calculated.ResultsSmoking and NAT2 rs1495741 interacted strongly, positively on aggressive UC on both the multiplicative (p = 0.004) and additive (p = 0.0002) scale, which was not observed for non-aggressive UC (pinteractions ≥ 0.6). This manifested in a higher HR of aggressive UC by ever smoking for the slow acetylation NAT2 genotype (HR, 5.00 [95% confidence interval, 2.67–9.38]) than for intermediate/fast acetylation NAT2 (HR, 1.50 [0.83–2.71]), and in differences in absolute risks by smoking and NAT2 genotype. Smoking also interacted additively and positively with the GRS on any UC (p = 0.01) and non-aggressive UC (p = 0.02), but not on aggressive UC (p = 0.1). Gene-smoking interactions of lesser magnitude than for NAT2 were found for SNPs in APOBEC3A, SLC14A1 and MYNN.ConclusionsThis study suggests that smoking increases UC risk more than expected when combined with certain genetic risks. Individuals with the slow acetylation NAT2 variant might particularly benefit from smoking intervention to prevent lethal UC; however, replication in larger studies is needed.
|
|
