| 1. |
- Machiela, Mitchell J, et al.
(författare)
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Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:5, s. 747-754
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.
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| 2. |
- Laskar, Ruhina S, et al.
(författare)
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Sex specific associations in genome wide association analysis of renal cell carcinoma.
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 27:10, s. 1589-1598
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.
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| 3. |
- Scelo, Ghislaine, et al.
(författare)
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Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
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| 4. |
- Preston, Mark A., et al.
(författare)
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Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate Cancer in Black Men
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 75:3, s. 399-407
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate-specific antigen (PSA) measurement in midlife predicts long-term prostate cancer (PCa) mortality among white men. Objective: To determine whether baseline PSA level during midlife predicts risk of aggressive PCa in black men. Design, setting, and participants: Nested case-control study among black men in the Southern Community Cohort Study recruited between 2002 and 2009. A prospective cohort in the southeastern USA with recruitment from community health centers. A total of 197 incident PCa patients aged 40–64 yr at study entry and 569 controls matched on age, date of blood draw, and site of enrollment. Total PSA was measured in blood collected and stored at enrollment. Outcome measurements and statistical analysis: Total and aggressive PCa (91 aggressive: Gleason ≥7, American Joint Committee on Cancer stage III/IV, or PCa-specific death). Exact conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) for PCa by category of baseline PSA. Results and limitations: Median PSA among controls was 0.72, 0.80, 0.94, and 1.03 ng/ml for age groups 40–49, 50–54, 55–59, and 60–64 yr, respectively; 90th percentile levels were 1.68, 1.85, 2.73, and 3.33 ng/ml. Furthermore, 95% of total and 97% of aggressive cases had baseline PSA above the age-specific median. Median follow-up was 9 yr. The OR for total PCa comparing PSA >90th percentile versus ≤median was 83.6 (95% CI, 21.2–539) for 40–54 yr and 71.7 (95% CI, 23.3–288) for 55–64 yr. For aggressive cancer, ORs were 174 (95% CI, 32.3–infinity) for 40–54 yr and 51.8 (95% CI, 11.0–519) for 55–64 yr. A composite endpoint of aggressive PCa based on stage, grade, and mortality was used and is a limitation. Conclusions: PSA levels in midlife strongly predicted total and aggressive PCa among black men. PSA levels among controls were similar to those among white controls in prior studies. Patient summary: Prostate-specific antigen (PSA) level during midlife strongly predicted future development of aggressive prostate cancer among black men. Targeted screening based on a midlife PSA might identify men at high risk while minimizing screening in those men at low risk. Prostate-specific antigen (PSA) level during midlife strongly predicted total and aggressive prostate cancer among black men. Risk-stratified screening based on midlife PSA might retain the benefits of screening while reducing harms.
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| 5. |
- Bosette, C, et al.
(författare)
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A pooled analysis of case-control studies of thyroid cancer. VII. Cruciferous and other vegetables (International)
- 2002
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Ingår i: Cancer Causes and Control. - 0957-5243 .- 1573-7225. ; 13:8, s. 765-775
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association between cruciferous and other vegetables and thyroid cancer risk we systematically reanalyzed the original data from 11 case-control studies conducted in the US, Asia, and Europe. Methods: A total of 2241 cases (1784 women, 457 men) and 3716 controls (2744 women, 972 men) were included. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Summary ORs for all studies combined were computed as the weighted average of the estimates from each study. Results: A decreased risk for the highest level of cruciferous vegetable intake, as compared to the lowest, was observed in Los Angeles, Hawaii, Connecticut, southeastern Sweden, Troms°, and Switzerland, the OR were above unity in Japan and Uppsala, whereas no material association was found in northern Sweden, Italy, or Greece. The OR values for all studies combined were 0.87 (95% CI 0.75-1.01) for moderate and 0.94 (95% CI 0.80-1.10) for high cruciferous vegetables intake. The results were similar in studies from iodine-rich areas and endemic goiter areas, and were consistent when the analysis was restricted to papillary carcinomas and women. The summary OR values for vegetables other than cruciferous were 1.04 (0.88-1.22) for moderate and 0.82 (0.69-0.98) for high consumption. Conclusions: This combined analysis indicates that cruciferous vegetables are not positively related to thyroid cancer risk. Their effect does not seem to be substantially different from that of other vegetables, which appear to be protective on this cancer.
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| 6. |
- Bosetti, C, et al.
(författare)
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A pooled analysis of case-control studies of thyroid cancer. VI. Fish and shellfish consumption
- 2001
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Ingår i: Cancer Causes and Control. - 0957-5243 .- 1573-7225. ; 12:4, s. 375-382
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To better understand the role of fish and shellfish on thyroid cancer risk, we systematically re-analyzed the original data from 13 case-control studies conducted in the US, Japan, China, and Europe. Methods: A total of 2497 cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Combined ORs were computed as the weighted average of the estimates from each study. Results: The ORs for the highest level of total fish consumption (three or more times per week) as compared to the lowest one (less than once per week) was above unity in Hawaii, Connecticut, Japan, Norway, Troms°, and Vaud. Conversely, the ORs for the studies in Los Angeles, Shanghai, southeastern Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The pattern of risk for salt water fish and shellfish was not substantially different from that of total fish. Fish was not associated with thyroid cancer risk in all studies combined (OR = 0.99, 95% CI 0.85-1.2 for moderate, and OR=0.88, 95% CI 0.71-1.1 for high total fish consumption), but there was a suggestion of a protective effect in endemic goiter areas (OR = 0.65, 95% CI 0.48-0.88). Conclusion: This combined analysis indicates that relatively elevated fish consumption does not appreciably increase thyroid cancer risk, and may have a favorable influence in areas where iodine deficiency is, or was, common.
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| 7. |
- Dal Maso, L, et al.
(författare)
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A pooled analysis of thyroid cancer studies. V. Anthropometric factors
- 2000
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Ingår i: Cancer Causes and Control. - 0957-5243 .- 1573-7225. ; 11:2, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the relation between anthropometric factors and thyroid cancer risk in a pooled analysis of individual data from 12 case-control studies conducted in the US, Japan, China and Europe. Methods: 2056 female and 417 male cases, 3358 female and 965 male controls were considered. Odds ratios (OR) were derived from logistic regression, conditioning on age, A-bomb exposure (Japan) and study, and adjusting for radiotherapy. Results: Compared to the lowest tertile of height, the pooled OR was 1.2 for females for the highest one, and 1.5 for males, and trends in risk were significant. With reference to weight at diagnosis, the OR for females was 1.2 for the highest tertile, and the trend in risk was significant, whereas no association was observed in males. Body mass index (BMI) at diagnosis was directly related to thyroid cancer risk in females (OR = 1.2 for the highest tertile), but not in males. No consistent pattern of risk emerged with BMI during the late teens. Most of the associations were observed both for papillary and follicular cancers, and in all age groups. However, significant heterogeneity was observed across studies. Conclusions: Height and weight at diagnosis are moderately related to thyroid cancer risk.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Preston, Mark A, et al.
(författare)
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Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal Prostate Cancer
- 2016
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 34:23, s. 2705-11
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific antigen (PSA) level in midlife predicted future prostate cancer (PCa) mortality in an unscreened Swedish population. Our purpose was to determine if a baseline PSA level during midlife predicts lethal PCa in a US population with opportunistic screening.We conducted a nested case-control study among men age 40 to 59 years who gave blood before random assignment in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and β-carotene among 22,071 US male physicians initiated in 1982 and then transitioned into a prospective cohort with 30 years of follow-up. Baseline PSA levels were available for 234 patients with PCa and 711 age-matched controls. Seventy-one participants who developed lethal PCa were rematched to 213 controls. Conditional logistic regression was used to estimate odds ratios and the area under the receiver operating characteristic curve, with 95% CIs, of the association between baseline PSA and risk of lethal PCa.Median PSA among controls was 0.68, 0.88, and 0.96 ng/mL for men age 40 to 49, 50 to 54, and 55 to 59 years, respectively. Risk of lethal PCa was strongly associated with baseline PSA in midlife: odds ratios (95% CIs) comparing PSA in the > 90th percentile versus less than or equal to median were 8.7 (1.0 to 78.2) at 40 to 49 years, 12.6 (1.4 to 110.4) at 50 to 54 years, and 6.9 (2.5 to 19.1) at 55 to 59 years. A total of 82%, 71%, and 86% of lethal cases occurred in men with PSA above the median at ages 40 to 49, 50 to 54, and 55 to 59 years, respectively.PSA levels in midlife strongly predict future lethal PCa in a US cohort subject to opportunistic screening. Risk-stratified screening on the basis of midlife PSA should be considered in men age 45 to 59 years.
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| 14. |
- Carlsson, Sigrid, 1982, et al.
(författare)
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A Provider-Facing Decision Support Tool for Prostate Cancer Screening in Primary Care: A Pilot Study
- 2024
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Ingår i: APPLIED CLINICAL INFORMATICS. - 1869-0327. ; 15:02, s. 274-281
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Our objective was to pilot test an electronic health record-embedded decision support tool to facilitate prostate-specific antigen (PSA) screening discussions in the primary care setting. Methods We pilot-tested a novel decision support tool that was used by 10 primary care physicians (PCPs) for 6 months, followed by a survey. The tool comprised (1) a risk-stratified algorithm, (2) a tool for facilitating shared decision-making (Simple Schema), (3) three best practice advisories (BPAs: <45, 45-75, and >75 years), and (4) a health maintenance module for scheduling automated reminders about PSA rescreening. Results All PCPs found the tool feasible, acceptable, and clear to use. Eight out of ten PCPs reported that the tool made PSA screening conversations somewhat or much easier. Before using the tool, 70% of PCPs felt confident in their ability to discuss PSA screening with their patient, and this improved to 100% after the tool was used by PCPs for 6 months. PCPs found the BPAs for eligible (45-75 years) and older men (>75 years) more useful than the BPA for younger men (<45 years). Among the 10 PCPs, 60% found the Simple Schema to be very useful, and 50% found the health maintenance module to be extremely or very useful. Most PCPs reported the components of the tool to be at least somewhat useful, with 10% finding them to be very burdensome. Conclusion We demonstrated the feasibility and acceptability of the tool, which is notable given the marked low acceptance of existing tools. All PCPs reported that they would consider continuing to use the tool in their clinic and were likely or very likely to recommend the tool to a colleague.
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| 15. |
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| 16. |
- Yim, Kendrick, et al.
(författare)
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Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial
- 2023
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Ingår i: The Journal of urology. - 1527-3792. ; 210:4, s. 630-638
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We studied whether adding percent free prostate-specific antigen (%fPSA) to total PSA improves prediction of clinically significant prostate cancer (csPCa) and fatal PCa.METHODS: 6727 men within the intervention arm of the Prostate, Lung, Colorectal and Ovarian Trial had baseline %fPSA. Of this cohort, 475 had csPCa and 98 had fatal PCa. Cumulative incidence and Cox analyses were conducted to evaluate the association between %fPSA/PSA and csPCa/fatal PCa. Harrell's concordance-index (C-index) evaluated predictive ability. Kaplan-Meier analysis assessed survival.RESULTS: Median follow-up was 19.7 years, median baseline PSA was 1.19 ng/mL, median %fPSA was 18%. Cumulative incidence of fatal PCa for men with baseline PSA≥2 ng/mL and %fPSA ≤10 was 3.2% and 6.1% at 15 and 25 years, compared to 0.03% and 1.1% for men with %fPSA >25%. In younger men (55-64 yr) with baseline PSA 2-10 ng/mL, C-index improved from 0.56 to 0.60 for csPCa and from 0.53 to 0.64 for fatal PCa with addition of %fPSA. In older men (65-74 yr), C-index improved for csPCa from 0.60 to 0.66, while no improvement in fatal PCa. Adjusting for age, digital rectal exam, family history of PCa, and total PSA, %fPSA was associated with csPCa (HR 1.05, P < .001) per 1% decrease. %fPSA improved prediction of csPCa and fatal PCA for all race groups. CONCLUSION: In a large US screening trial, the addition of %fPSA to total PSA in men with baseline PSA ≥2 ng/mL improved prediction of csPCa and fatal PCa. Free PSA should be used to risk-stratify screening and decrease unnecessary prostate biopsies.
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