| 1. |
- Anantharaman, Devasena, et al.
(författare)
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No causal association identified for human papillomavirus infections in lung cancer
- 2014
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 74:13, s. 3525-3534
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case-control studies (retrospective) and one nested case-control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer. (C) 2014 AACR.
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| 2. |
- Bosetti, Cristina, et al.
(författare)
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High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries
- 2011
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 129:1, s. 173-179
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Tidskriftsartikel (refereegranskat)abstract
- Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.
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| 3. |
- Honda, Kazufumi, et al.
(författare)
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CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer : a prospective evaluation
- 2019
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 144:8, s. 1877-1887
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.
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| 4. |
- Johansson, Mattias, et al.
(författare)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 5. |
- Koivisto-Korander, Riitta, et al.
(författare)
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Second primary malignancies among women with uterine sarcoma
- 2012
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 126:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Uterine sarcomas (US) are rare malignancies with unclear aetiology. Studies on uterine sarcomas in the setting of second primary malignant tumours can provide clues to aetiology and identify side effects of different treatments. Methods. A cohort of 8606 cases of US was extracted from the data from 13 cancer registries and followed for second primary cancers within the period 1943-2000. Standardized incidence ratios (SIRs) were calculated, and Poisson regression analyses were performed. Results. There were 499 cancer cases observed after a first diagnosis of US (SIR 1.26, 95%CI 1.16-1.38). SIRs were elevated for cancers of the mouth and pharynx (2.16, 95%CI 1.15-3.69), colorectum (1.60, 95%CI 1.28-1.98), lung (1.73, 95%CI 1.27-2.29), breast (1.25, 95%CI 1.05-1.49), urinary bladder (1.74, 95%CI 1.02-2.79), kidney (2.00, 95%CI 1.24-3.06), thyroid gland (2.74, 95%CI 1.42-4.79), and soft tissue sarcoma (5.23, 95%CI 2.51-9.62). The risk of breast cancer increased along with increasing age of US diagnosis (p trend 0.040). The risk of kidney cancer increased along with decreasing age of US diagnosis (p trend 0.004) and short time since the US diagnosis (p trend 0.018). Conclusions. Our study demonstrated increased risk of certain cancers following a diagnosis of US. The elevated risk for breast cancer may indicate shared hormonal aetiology, while the increased risk of colorectal and bladder cancers after US may be caused by radiation therapy of US. The clustering of smoking-related cancers after US is worth exploring in the future. (c) 2012 Elsevier Inc. All rights reserved.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Maule, Milena, et al.
(författare)
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Second malignancies after childhood noncentral nervous system solid cancer: results from 13 cancer registries
- 2011
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 129:8, s. 1940-1952
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Tidskriftsartikel (refereegranskat)abstract
- Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adverse late effects, including second malignant neoplasm. The aim of our study was to assess the risk of specific second malignancies after a childhood NCNSSC. Diagnosis and follow-up data on 10,988 cases of NCNSSC in children (0-14 years) were obtained from 13 registries. Standardized incidence ratios (SIRs) with 95% confidence intervals (CI) and cumulative incidence of second malignancies were computed. We observed 175 second malignant neoplasms, yielding a SIR of 4.6, 95% CI: 3.9-5.3. When considering second cancers with at least 10 occurrences, highest relative risks were found for second malignant bone tumors (SIR = 26.4, 16.6-40.0), soft tissue sarcomas (SIR = 14.1, 6.7-25.8) and myeloid leukemia (SIR = 12.7, 6.3-22.8). Significant increased risks for all malignancies combined were observed after sympathetic nervous system tumors (SIR = 11.4, 5.2-21.6), retinoblastomas (SIR = 7.3, 5.4-9.8), renal tumors (SIR = 5.7, 3.8-8.0), malignant bone tumors (SIR = 5.6, 3.7-8.2), soft tissue sarcomas (SIR = 4.7, 3.2-6.8), germ-cell, trophoblastic and other gonadal neoplasms (SIR = 2.5, 1.1-4.9), carcinomas and other malignant epithelial neoplasms (SIR = 2.2, 1.4-3.3). The highest risk of a second malignancy of any type occurred 5 to 9 years after NCNSSC (SIR = 9.9, 6.8-13.9). The cumulative incidence of second malignancies 10 years after the first neoplasm was eight times higher among NCNSSC survivors than in the general population, with the absolute difference between observed and expected cumulative incidence still increasing after 50 years of follow-up. Children who survived a NCNSSC experience a large increased risk of developing a new malignancy, even many years after their initial diagnosis.
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| 9. |
- McKay, James D., et al.
(författare)
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Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes
- 2017
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 49:7, s. 1126-1132
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Tidskriftsartikel (refereegranskat)abstract
- Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
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| 10. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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