| 1. |
- Borgquist, Signe, et al.
(författare)
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Apo-lipoproteins, lipids and risk of cancer.
- 2016
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 138:11, s. 2648-2656
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Tidskriftsartikel (refereegranskat)abstract
- The epidemiological evidence for an obesity-cancer association is solid, whereas the association between obesity-associated lipoprotein levels and cancer is less evident. We investigated circulating levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) and association to risk of overall cancer and common cancer forms. The Malmö Diet and Cancer Study, a population-based prospective cohort study, enrolled 17,035 women and 11,063 men (1991-1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow-up, Jan 1(st) 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort, and HDL-C and LDL-C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HRadj ApoA1=0.98, 95%CI: 0.95,1.01; HRadj ApoB=1.01, 95%CI: 0.98-1.04). Among men, ApoB was positively associated with cancer risk (HRadj ApoB=1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HRadj =0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HRadj =0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HRadj =1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HRadj =1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung, and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer. This article is protected by copyright. All rights reserved.
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| 2. |
- Drake, Isabel, et al.
(författare)
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Lifestyle and cancer incidence and mortality risk depending on family history of cancer in two prospective cohorts
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:5, s. 1198-1207
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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.
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| 3. |
- Drake, Isabel, et al.
(författare)
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Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 141:6, s. 1170-1180
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44–73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow-up, and body mass index (BMI) and waist circumference (WC) at baseline. Multivariable cause-specific hazard ratios (HR) and subdistribution hazard ratios (sHR), taking into account noncancer deaths, were estimated using Cox- and competing risk regression. During follow-up (mean 17 years), 7,061 incident cancers (3,220 obesity-related cancer types) and 2,848 cancer deaths occurred. BMI and WC were associated with increased risk of obesity-related cancer incidence and cancer mortality. In T2D subjects, risk of obesity-related cancer was elevated among men (HR = 1.31, 95% CI: 1.12–1.54; sHR = 1.29, 95% CI: 1.10–1.52), and cancer mortality among both men and women (HR = 1.34, 95% CI: 1.20–1.49; sHR = 1.30, 95% CI: 1.16–1.45). There was no elevated actual risk of cancer death in T2D patients with long disease duration (sHR = 1.00, 95% CI: 0.83–1.20). There was a significant additive effect of T2D and adiposity on risk of obesity-related cancer and cancer mortality. In conclusion, detection bias may partially explain the increased risk of cancer morbidity among T2D patients. Both excess risk of competing events among patients with T2D and depletion of susceptibles due to earlier cancer detection will lower the actual risk of cancer, particularly with longer diabetes duration and at older ages.
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| 4. |
- Jochems, Sylvia H.J., et al.
(författare)
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Height, body mass index, and prostate cancer risk and mortality by way of detection and cancer risk category
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 147:12, s. 3328-3338
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a risk factor for advanced, but not localised, prostate cancer (PCa), and for poor prognosis. However, the detection of localised PCa through asymptomatic screening might influence these associations. We investigated height and body mass index (BMI) among 431 902 men in five Swedish cohorts in relation to PCa risk, according to cancer risk category and detection mode, and PCa-specific mortality using Cox regression. Statistical tests were two-sided. Height was positively associated with localised intermediate-risk PCa (HR per 5 cm, 1.03, 95% CI 1.01 to 1.05), while overweight and obesity were negatively associated with localised low- and intermediate-risk PCa (HRs per 5 kg/m2 , 0.86, 95% CI 0.81 to 0.90, and 0.92, 95% CI 0.88 to 0.97). However, these associations were partially driven by PCa's detected by asymptomatic screening and, for height, also by symptoms unrelated to PCa. The HR of localised PCa's, per 5 kg/m2 , was 0.88, 95% CI 0.83 to 0.92 for screen-detected PCa's, and 0.96, 95% CI 0.90 to 1.01 for PCa's detected through lower urinary tract symptoms. BMI was positively associated with PCa-specific mortality in the full population and in case-only analysis of each PCa risk category (HRs per 5 kg/m2 , 95% CI 1.11 to 1.22, P for heterogeneity = 0.14). More active health-seeking behaviour among tall and normal-weight men may partially explain their higher risk of localised PCa. The higher PCa-specific mortality among obese men accros all PCa risk categories in our study suggests obesity as a potential target to improve the prognosis of obese PCa patients.
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| 5. |
- Jochems, Sylvia, et al.
(författare)
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Waist circumference and a body shape index and prostate cancer risk and mortality
- 2021
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Ingår i: Cancer Medicine. - : Blackwell Publishing. - 2045-7634. ; 10:8, s. 2885-2896
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Tidskriftsartikel (refereegranskat)abstract
- We recently found a negative association between body mass index (BMI) and the risk of localised prostate cancer (PCa), no association with advanced PCa, and a positive association with PCa‐specific mortality. In a 15% subpopulation of that study, we here investigated the measures of abdominal adiposity including waist circumference (WC) and A Body Shape Index (ABSI) in relation to PCa risk and mortality. We used data from 58,457 men from four Swedish cohorts to assess WC and ABSI in relation to PCa risk according to cancer risk category, including localised asymptomatic and symptomatic PCa and advanced PCa, and PCa‐specific mortality. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During, on average, 10 years of follow‐up, 3290 men were diagnosed with PCa and 387 died of PCa. WC was negatively associated with the risk of total PCa (HR per 10 cm, 0.95; 95% CI 0.92–0.99), localised PCa (HR per 10 cm, 0.93, 95% CI 0.88–0.96) and localised asymptomatic PCa cases detected through a prostate‐specific antigen (PSA) test (HR per 10 cm, 0.87, 95% CI 0.81–0.94). WC was not associated with the risk of advanced PCa (HR per 10 cm, 1.02, 95% CI 0.93–1.14) or with PCa‐specific mortality (HR per 10 cm, 1.04, 95% CI 0.92–1.19). ABSI showed no associations with the risk of PCa or PCa‐specific mortality. While the negative association between WC and the risk of localised PCa was partially driven by PSA‐detected PCa cases, no association was found between abdominal adiposity and clinically manifest PCa in our population.
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| 6. |
- Orho-Melander, Marju, et al.
(författare)
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Blood lipid genetic scores, the HMGCR gene and cancer risk : A Mendelian randomization study
- 2018
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 47:2, s. 495-505
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unclear whether there are causal associations between blood lipids, statin use and cancer risks. Under certain assumptions, Mendelian randomization analysis of a genetic marker for an exposure eliminates reverse causation and confounding. Methods: We applied Mendelian randomization analysis to genetic scores, comprising 26–41 single-nucleotide polymorphisms (SNPs), as instrumental variables (IVs) for triglycerides and low- and high-density lipoprotein cholesterol (LDLC, HDLC), using a prospective cohort of 26 904 individuals in which there were 6607 incident cancers. We also investigated cancer risk for a SNP (rs12916) in the gene encoding hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the targeted enzyme in statin treatment. We used logistic regression and SNP pleiotropy-adjusted analyses to estimate the odds ratio per standard deviation (OR). Results: The OR for the triglyceride IV as a predictor of any cancer was 0.91 [95% confidence interval (CI): 0.80–1.03] unadjusted, and 0.87 (95% CI: 0.78–0.95) from the pleiotropy-adjusted analysis. For the HMGCR rs12916 per LDLC-lowering T-allele, the OR was 1.09 (95% CI: 1.01–1.18) for prostate cancer and 0.89 (95% CI: 0.82–0.96) for breast cancer. The LDLC IV was not associated with prostate cancer or breast cancer. There were no associations between IVs and cancers of the lung, colon or bladder. Conclusions: Under the assumptions of Mendelian randomization, there is a causal and negative association between serum triglycerides and risk of any cancer. Further, the HMGCR genetic variant might be associated with risks of prostate and breast cancers but the biological mechanisms behind these findings are unclear, as the LDLC IV was not associated with these cancers.
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| 7. |
- Rukh, Gull, et al.
(författare)
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Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age
- 2016
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 40:2, s. 252-259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVE: Genome-wide-association studies have identified numerous body mass index (BMI)-associated variants, but it is unclear how these relate to weight gain in adults at different ages.METHODS: We examined the association of a genetic risk score (GRS), consisting of 31 BMI-associated variants, with an annual weight change (AWC) and a substantial weight gain (SWG) of 10% by comparing self-reported weight at 20 years (y) with baseline weight (mean: 58 y; s.d.: 8 y) in 21407 participants from the Malmö Diet and Cancer Study (MDCS), and comparing baseline weight to weight at follow-up (mean: 73 y; s.d.: 6 y) among 2673 participants. Association between GRS and AWG and SWG was replicated in 4327 GLACIER (Gene x Lifestyle interactions And Complex traits Involved in Elevated disease Risk) participants (mean: 45 y; s.d.: 7 y) with 10 y follow-up. Cohort-specific results were pooled by fixed-effect meta-analyses.RESULTS: In MDCS, the GRS was associated with increased AWC (β: 0.003; s.e: 0.01; P: 7 × 10(-8)) and increased odds for SWG (odds ratio (OR) 1.01 (95% confidence interval (CI): 1.00, 1.02); P: 0.013) per risk-allele from age 20y, but unexpectedly with decreased AWC (β: -0.006; s.e: 0.002; P: 0.009) and decreased odds for SWG OR 0.96 (95% CI: 0.93, 0.98); P: 0.001) between baseline and follow-up. Effect estimates from age 20 y to baseline differed significantly from those from baseline to follow-up (P: 0.0002 for AWC and P: 0.0001 for SWG). Similar to MDCS, the GRS was associated with decreased odds for SWG OR 0.98 (95% CI: 0.96, 1.00); P: 0.029) from baseline to follow-up in GLACIER. In meta-analyses (n=7000), the GRS was associated with decreased AWC (β: -0.005; s.e.m. 0.002; P: 0.002) and decreased odds for SWG OR 0.97 (95% CI: 0.96, 0.99); P: 0.001) per risk-allele.CONCLUSIONS: Our results provide convincing evidence for a paradoxical inversed relationship between a high number of BMI-associated risk-alleles and less weight gain during and after middle-age, in contrast to the expected increased weight gain seen in younger age.
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| 8. |
- Teleka, Stanley, et al.
(författare)
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Association between blood pressure and BMI with bladder cancer risk and mortality in 340,000 men in three Swedish cohorts
- 2021
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 10:4, s. 1431-1438
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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.
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| 9. |
- Teleka, Stanley, et al.
(författare)
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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
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11 November
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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.
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| 10. |
- Teleka, Stanley, et al.
(författare)
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Interaction between blood pressure and genetic risk score for bladder cancer, and risk of urothelial carcinoma in men.
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1, s. 18336-
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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.
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