| 191. |
- Stocks, Tanja, et al.
(författare)
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Metabolic risk score and cancer risk : pooled analysis of seven cohorts
- 2015
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 44:4, s. 1353-1363
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are few data on the joint influence of metabolic factors on risk of separate cancers. Methods: We analysed data on body mass index, blood pressure and plasma levels of glucose, total cholesterol and triglycerides from seven European cohorts comprising 564 596 men and women with a mean age of 44 years. We weighted those factors equally into a standardized metabolic risk score [MRS, mean = 0, standard deviation (SD) = 1], with an individual's level indicated as SDs from the sex-and cohort-specific means. Cancer hazard ratios were calculated by Cox regression with age as timescale and with relevant adjustments including smoking status. All statistical tests were two-sided. Results: During a mean follow-up of 12 years, 21 593 men and 14 348 women were diagnosed with cancer. MRS was linearly and positively associated with incident cancer in total and at sites (P<0.05). In men, risk per SD MRS was increased by 43% (95% confidence interval: 27-61) for renal cell cancer, 43% (16-76) for liver cancer, 29% (20-38) for colon cancer, 27% (5-54) for oesophageal cancer, 20% (9-31) for rectal cancer, 19% (4-37) for leukaemias, 15% (1-30) for oral cancer and 10% (2-19) for bladder cancer. In women, risk increases per SD MRS were 56% (42-70) for endometrial cancer, 53% (29-81) for pancreatic cancer, 40% (16-67) for renal cell cancer, 27% (9-47) for cervical cancer and 17% (3-32) for rectal cancer. Conclusion: This largest study to date on the joint influence of metabolic factors on risk of separate cancers showed increased risks for several cancers, in particular renal cell and liver cancer in men and endometrial and pancreatic cancer in women.
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| 192. |
- Sun, Ming, et al.
(författare)
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Metabolically (un)healthy obesity and risk of obesity-related cancers : a pooled study
- 2023
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:4, s. 456-467
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of obesity with or without metabolic aberrations, commonly termed metabolically unhealthy or healthy obesity, in relation to cancer risk are scarce.Methods: We investigated body mass index (normal weight, overweight, obesity) jointly and in interaction with metabolic health status in relation to obesity-related cancer risk (n = 23630) among 797193 European individuals. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to define metabolically healthy and unhealthy status. Hazard ratios (HRs) and multiplicative interactions were assessed using Cox regression, and additive interactions were assessed using the relative excess risk for interaction. All statistical tests were 2-sided.Results: Metabolically unhealthy obesity, with a baseline prevalence of 7%, was, compared with metabolically healthy normal weight, associated with an increased relative risk of any obesity-related cancer and of colon, rectal, pancreas, endometrial, liver, gallbladder, and renal cell cancer (P <. 05), with the highest risk estimates for endometrial, liver, and renal cell cancer (HR = 2.55-3.00). Metabolically healthy obesity showed a higher relative risk for any obesity-related cancer and colon (in men), endometrial, renal cell, liver, and gallbladder cancer, though the risk relationships were weaker. There were no multiplicative interactions, but there were additive, positive interactions between body mass index and metabolic health status on obesity-related and rectal cancer among men and on endometrial cancer (P <. 05).Conclusions: This study highlights that the type of metabolic obesity phenotype is important when assessing obesity-related cancer risk. In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.
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| 193. |
- Van Hemelrijck, Mieke, et al.
(författare)
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Longitudinal study of body mass index, dyslipidemia, hyperglycemia, and hypertension in 60,000 men and women in Sweden and Austria
- 2018
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is suggested to underlie development of other metabolic aberrations, but longitudinal relationships between metabolic factors at various ages has not been studied in detail. Methods: Data from 27,379 men and 32,275 women with in total 122,940 health examinations in the Västerbotten Intervention Project, Sweden and the Vorarlberg Health Monitoring and Prevention Programme, Austria were used to investigate body mass index (BMI), mid-blood pressure, and fasting levels of glucose, triglycerides, and total cholesterol at baseline in relation to 10-year changes of these factors and weight. We included paired examinations performed 10 +/- 2 years apart and used them for longitudinal analysis with linear regression of changes between the ages 30 and 40, 40 and 50, or 50 and 60 years. Results: Higher levels of BMI were associated with increases in glucose and mid-blood pressure as well as triglycerides levels, and, to a lesser extent, decreases in cholesterol levels. For instance, per 5 kg/m(2) higher BMI at age 40, glucose at age 50 increased by 0.24 mmol/l (95%Cl:0.22-0.26) and mid-blood pressure increased by 1.54 mm Hg (95%Cl: 1.35-1.74). The strongest association observed was between BMI at age 30 and mid-blood pressure, which was 2.12 mm Hg (95% CI: 1.79-2.45) increase over ten years per 5 kg/m(2) higher BMI level. This association was observed at an age when blood pressure levels on average remained stable. Other associations than those with BMI at baseline were much weaker. However, triglyceride levels were associated with future glucose changes among individuals with elevated BMI, particularly in the two older age groups. Conclusion: BMI was most indicative of long-term changes in metabolic factors, and the strongest impact was observed for increases in blood pressure between 30 and 40 years of age. Our study supports that lifestyle interventions preventing metabolic aberrations should focus on avoiding weight increases.
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| 194. |
- Vertosick, Emily A, et al.
(författare)
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Prespecified Four Kallikrein Marker Model (4Kscore) at Age 50 or 60 for Early Detection of Lethal Prostate Cancer in a Large Population-Based Cohort of Asymptomatic Men Followed for 20 Years.
- 2020
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Ingår i: Journal of Urology. - : Lippincott Williams & Wilkins. - 0022-5347 .- 1527-3792. ; 204:2, s. 281-288
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A prespecified statistical model based on 4 kallikrein markers in blood, commercially available as the 4Kscore®, has been shown to accurately detect high grade (greater than Grade Group 2) prostate cancer in men with moderately elevated prostate specific antigen. We assessed whether the model predicted prostate cancer metastasis or death in men not subject to prostate specific antigen screening.Materials and Methods: The cohort includes 43,692 unscreened prostate cancer-free men from a Swedish population based cohort with low rates of prostate specific antigen screening (Västerbotten Intervention Project). Using cryopreserved blood collected at ages 50 and 60 years from men in this cohort we analyzed the association between prostate specific antigen and other kallikrein marker levels in blood and risk of prostate cancer metastasis or death.Results: There were 308 with metastases and 172 prostate cancer deaths. Baseline prostate specific antigen was strongly associated with 20-year risk of prostate cancer death (c-index at age 50, 0.859, 95% CI 0.799–0.916; age 60, 0.840, 95% CI 0.799–0.878). Men 60 years old with prostate specific antigen below median (less than 1.2 ng/ml) had 0.4% risk of prostate cancer death at 20 years. Among men with moderately elevated prostate specific antigen (2.0 ng/ml or greater) the 4Kscore markedly improved discrimination (c-index 0.767 vs 0.828 and 0.774 vs 0.862 in men age 50 and 60, respectively). Long-term risk of prostate cancer death or metastasis in men with low 4Kscores was very low.Conclusions: Screening should focus on men in top prostate specific antigen quartile at age 60 years. Men with elevated prostate specific antigen but a low 4Kscore can safely be monitored with repeated blood markers in place of immediate biopsy.
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| 195. |
- Wirén, Sara, et al.
(författare)
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Pooled cohort study on height and risk of cancer and cancer death
- 2014
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Ingår i: Cancer Causes and Control. - : Springer Berlin/Heidelberg. - 0957-5243 .- 1573-7225. ; 25:2, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To assess the association between height and risk of cancer and cancer death.METHODS: The metabolic syndrome and cancer project is a prospective pooled cohort study of 585,928 participants from seven cohorts in Austria, Norway, and Sweden. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model.RESULTS: During a mean follow-up of 12.7 years (SD = 7.2), 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer. Increased height (per 5-cm increment) was associated with an increased overall cancer risk in women, HR 1.07 (95 % CI 1.06-1.09), and in men, HR 1.04 (95 % CI 1.03-1.06). The highest HR was seen for malignant melanoma in women, HR 1.17 (95 % CI 1.11-1.24), and in men HR 1.12 (95 % CI 1.08-1.19). Height was also associated with increased risk of cancer death in women, HR 1.03 (95 % CI 1.01-1.16), and in men, HR 1.03 (95 % CI 1.01-1.05). The highest HR was observed for breast cancer death in postmenopausal women (>60 years), HR 1.10 (95 % CI 1.00-1.21), and death from renal cell carcinoma in men, HR 1.18 (95 % CI 1.07-1.30). All these associations were independent of body mass index.CONCLUSION: Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.
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| 196. |
- Wood, Angela M., et al.
(författare)
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The Inverse Association of Body Mass Index with Lung Cancer : Exploring Residual Confounding, Metabolic Aberrations and Within-Person Variability in Smoking
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 30:8, s. 1489-1497
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Tidskriftsartikel (refereegranskat)abstract
- Background: The inverse observational association between body mass index (BMI) and lung cancer risk remains unclear. We assessed whether the association is explained by metabolic aberrations, residual confounding, and within-person variability in smoking, and compared against other smoking-related cancers. Methods: We investigated the association between BMI, and its combination with a metabolic score (MS) of mid-blood pressure, glucose, and triglycerides, with lung cancer and other smokingrelated cancers in 778,828 individuals. We used Cox regression, adjusted and corrected for within-person variability in smoking (status/pack-years), calculated from 600,201 measurements in 221,958 participants. Results: Over a median follow-up of 20 years, 20,242 smoking-related cancers (6,735 lung cancers) were recorded. Despite adjustment and correction for substantial within-person variability in smoking, BMI remained inversely associated with lung cancer [HR per standard deviation increase, 0.87 (95% confidence interval 0.85-0.89)]. Individuals with BMI less than 25 kg/m(2) and high MS had the highest risk [HR 1.52 (1.44-1.60) vs. BMI >= 25 with low MS]. These associations were weaker and nonsignificant among nonsmokers. Similar associations were observed for head and neck cancers and esophageal squamous cell carcinoma, whereas for other smoking-related cancers, we generally observed positive associations with BMI. Conclusions: The increased lung cancer risk with low BMI and high MS is unlikely due to residual confounding and withinperson variability in smoking. However, similar results for other cancers strongly related to smoking suggest a remaining, unknown, effect of smoking. Impact: Extensive smoking-adjustments may not capture all the effects of smoking on the relationship between obesity-related factors and risk of smoking-related cancers.
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| 197. |
- Arthur, R., et al.
(författare)
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Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:11, s. 2254-2262
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.
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| 198. |
- Beckmann, Kerri, et al.
(författare)
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Androgen Deprivation Therapies and Changes in Comorbidity : A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer
- 2019
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Ingår i: European Urology. - : ELSEVIER SCIENCE BV. - 0302-2838 .- 1873-7560. ; 75:4, s. 676-683
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.
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| 199. |
- Beckmann, Kerri, et al.
(författare)
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Spironolactone use is associated with lower prostate cancer risk : a population-wide case-control study
- 2020
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Ingår i: Prostate Cancer and Prostatic Diseases. - : NATURE PUBLISHING GROUP. - 1365-7852 .- 1476-5608. ; 23:3, s. 527-533
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Tidskriftsartikel (refereegranskat)abstract
- Background Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties. Methods A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides. Results Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings. Conclusion PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.
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| 200. |
- Berndt, Sonja I, et al.
(författare)
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Large-scale fine mapping of the HNF1B locus and prostate cancer risk
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3322-3329
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 × 10(-8) with the most significant association with rs4430796 (P = 1.62 × 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2)= 0.64), rs7405696 was also associated with risk (P = 9.35 × 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 × 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 × 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer.
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