101 results on '"Mariosa D"'
Search Results
2. Survival benefit and additional value of preoperative chemoradiotherapy in resectable gastric and gastro-oesophageal junction cancer: A direct and adjusted indirect comparison meta-analysis
- Author
-
Kumagai, K., Rouvelas, I., Tsai, J.A., Mariosa, D., Lind, P.A., Lindblad, M., Ye, W., Lundell, L., Schuhmacher, C., Mauer, M., Burmeister, B.H., Thomas, J.M., Stahl, M., and Nilsson, M.
- Published
- 2015
- Full Text
- View/download PDF
3. A Mendelian randomization study of lifestyle factors and glycemic traits and risk of pancreatic cancer
- Author
-
Dimou, Niki, primary, Peruchet-Noray, L., additional, Mariosa, D., additional, Lu, Y., additional, Gentiluomo, M., additional, Campa, D., additional, Viallon, V., additional, Freisling, H., additional, Murphy, N., additional, Gunter, M., additional, Canzian, F., additional, and Ferrari, P., additional
- Published
- 2022
- Full Text
- View/download PDF
4. Body size at different ages and risk of six cancers: a Mendelian randomization and prospective cohort study
- Author
-
Mariosa, D, Smith-Byrne, K, Richardson, TG, and Perez-Cornago, A
- Abstract
It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for 6 obesity-related cancers, we performed univariable and multivariable analyses using 1) Mendelian randomization (MR) analysis and 2) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger early life body size was associated with higher risk of endometrial (odds ratioMR = 1.61, 95% confidence interval = 1.23 to 2.11) and kidney (odds ratioMR = 1.40, 95% confidence interval = 1.09 to 1.80) cancer. These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life body mass index (BMI) was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI.
- Published
- 2022
5. Physical and cognitive fitness in young adulthood and risk of amyotrophic lateral sclerosis at an early age
- Author
-
Longinetti, E., Mariosa, D., Larsson, H., Almqvist, C., Lichtenstein, P., Ye, W., and Fang, F.
- Published
- 2017
- Full Text
- View/download PDF
6. Response to the letter ‘Type 2 diabetes and amyotrophic lateral sclerosis’
- Author
-
Mariosa, D. and Fang, F.
- Published
- 2016
- Full Text
- View/download PDF
7. Association between diabetes and amyotrophic lateral sclerosis in Sweden
- Author
-
Mariosa, D., Kamel, F., Bellocco, R., Ye, W., and Fang, F.
- Published
- 2015
- Full Text
- View/download PDF
8. Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer
- Author
-
Ferreiro-Iglesias, A. McKay, J.D. Brenner, N. Virani, S. Lesseur, C. Gaborieau, V. Ness, A.R. Hung, R.J. Liu, G. Diergaarde, B. Olshan, A.F. Hayes, N. Weissler, M.C. Schroeder, L. Bender, N. Pawlita, M. Thomas, S. Pring, M. Dudding, T. Kanterewicz, B. Ferris, R. Thomas, S. Brhane, Y. Díez-Obrero, V. Milojevic, M. Smith-Byrne, K. Mariosa, D. Johansson, M.J. Herrero, R. Boccia, S. Cadoni, G. Lacko, M. Holcátová, I. Ahrens, W. Lagiou, P. Lagiou, A. Polesel, J. Simonato, L. Merletti, F. Healy, C.M. Hansen, B.T. Nygård, M. Conway, D.I. Wright, S. Macfarlane, T.V. Robinson, M. Alemany, L. Agudo, A. Znaor, A. Amos, C.I. Waterboer, T. Brennan, P.
- Subjects
stomatognathic diseases ,virus diseases - Abstract
Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC. © 2021, The Author(s).
- Published
- 2021
9. No association between biopsy-verified celiac disease and subsequent amyotrophic lateral sclerosis – a population-based cohort study
- Author
-
Ludvigsson, J. F., Mariosa, D., Lebwohl, B., and Fang, F.
- Published
- 2014
- Full Text
- View/download PDF
10. Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers: Metaanálisis de la morbilidad postoperatoria y de la mortalidad perioperatoria en pacientes que reciben quimioterapia o quimiorradioterapia neoadyuvante por cánceres de esófago o de la unión gastroesofágica
- Author
-
Kumagai, K., Rouvelas, I., Tsai, J. A., Mariosa, D., Klevebro, F., Lindblad, M., Ye, W., Lundell, L., and Nilsson, M.
- Published
- 2014
11. Antidiabetics, statins and the risk of amyotrophic lateral sclerosis
- Author
-
Mariosa, D., primary, Kamel, F., additional, Bellocco, R., additional, Ronnevi, L.‐O., additional, Almqvist, C., additional, Larsson, H., additional, Ye, W., additional, and Fang, F., additional
- Published
- 2020
- Full Text
- View/download PDF
12. Antibiotics use and risk of amyotrophic lateral sclerosis in Sweden
- Author
-
Sun, J., primary, Zhan, Y., additional, Mariosa, D., additional, Larsson, H., additional, Almqvist, C., additional, Ingre, C., additional, Zagai, U., additional, Pawitan, Y., additional, and Fang, F., additional
- Published
- 2019
- Full Text
- View/download PDF
13. Comorbidity of mitochondrial disease and dementia in patients with idiopathic polyneuropathy
- Author
-
Samuelsson, K., primary, Mariosa, D., additional, Fang, F., additional, and Press, R., additional
- Published
- 2018
- Full Text
- View/download PDF
14. Physical and cognitive fitness in young adulthood and risk of amyotrophic lateral sclerosis at an early age
- Author
-
Longinetti, E., primary, Mariosa, D., additional, Larsson, H., additional, Almqvist, C., additional, Lichtenstein, P., additional, Ye, W., additional, and Fang, F., additional
- Published
- 2016
- Full Text
- View/download PDF
15. CHLORATE AND CHLORITE EXPOSURE VIA DRINKING WATER DURING PREGNANCY AND THE RISK OF CONGENITAL ANOMALIES
- Author
-
Righi, Elena, Bechtold, PETRA ELISABETH, Mariosa, D, Mastroianni, Katia, Giacobazzi, Pierluigi, Predieri, Guerrino, Calzolari, E, Astolfi, G, Lauriola, P, Tortorici, D, Fantuzzi, Guglielmina, and Aggazzotti, Gabriella
- Subjects
congenital anomalies ,chlorate ,chlorite ,drinking water ,disinfection by products - Published
- 2011
16. Systematic review and meta-analysis on the significance of salvage esophagectomy for persistent or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy
- Author
-
Kumagai, K., primary, Mariosa, D., additional, Tsai, J. A., additional, Nilsson, M., additional, Ye, W., additional, Lundell, L., additional, and Rouvelas, I., additional
- Published
- 2015
- Full Text
- View/download PDF
17. Esposizione attraverso l’acqua potabile a cloriti e clorati durante la gravidanza e rischio di anomalie congenite
- Author
-
Righi, Elena, Bechtold, PETRA ELISABETH, Mariosa, D, Mastroianni, Katia, Giacobazzi, Pierluigi, Predieri, Guerrino, Calzolari, E, Astolfi, G, Lauriola, P, Tortorici, D, Fantuzzi, Guglielmina, and Aggazzotti, Gabriella
- Subjects
cloriti ,clorati ,gravidanza ,acqua potabile ,anomalie congenite - Published
- 2010
18. Esposizione a sottoprodotti della disinfezione delle acque potabili durante la gravidanza e anomalie congenite: risultati di uno studio di caso-controllo condotto nella Regione di Emilia-Romagna
- Author
-
Righi, Elena, Bechtold, PETRA ELISABETH, Mariosa, D, Mastroianni, Katia, Giacobazzi, Pierluigi, Predieri, Guerrino, Calzolari, E, Astolfi, G, Lauriola, P, Tortorici, D, Fantuzzi, Guglielmina, and Aggazzotti, Gabriella
- Subjects
cloriti ,sottoprodotti della disinfezione delle acque potabili ,clorati ,malformazioni congenite ,trialometani - Published
- 2010
19. Studio caso-controllo sull’esposizione a trialometani durante al gravidanza e rischio di anomalie congenite nella regione Emilia Romagna
- Author
-
Righi, Elena, Bechtold, PETRA ELISABETH, Mariosa, D, Mastroianni, Katia, Giacobazzi, Pierluigi, Predieri, Guerrino, Calzolari, E, Astolfi, G, Lauriola, P, Tortorici, D, Fantuzzi, Guglielmina, and Aggazzotti, Gabriella
- Subjects
gravidanza ,sottoprodotti disinfezione acque potabili ,trialometani ,malformazioni congenite - Published
- 2010
20. Systematic review and meta-analysis on the significance of salvage esophagectomy for persistent or recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy.
- Author
-
Kumagai, K., Mariosa, D., Tsai, J. A., Nilsson, M., Ye, W., Lundell, L., and Rouvelas, I.
- Subjects
- *
ESOPHAGEAL cancer , *ESOPHAGECTOMY , *CANCER radiotherapy , *CANCER chemotherapy , *CANCER-related mortality , *SYSTEMATIC reviews , *META-analysis - Abstract
The therapeutic strategy to be recommended in case of recurrent or persistent squamous cell esophageal cancer after completed definitive chemoradiotherapy (dCRT) has to be documented. Salvage esophagectomy has traditionally been recognized as a viable option, but many clinicians oppose the use of surgery due to the associated excessive morbidity and mortality. 'Second-line' chemoradiotherapy (CRT) without surgery may offer a treatment alternative in these difficult and demanding clinical situations. Until now, no comprehensive attempt has been carried out to compare the respective therapeutic options. A systematic literature search was performed focusing on studies comparing survival and treatment-related mortality in patients submitted to salvage esophagectomy or second-line CRT for recurrent or persistent esophageal squamous cell carcinoma after dCRT. Hazard ratios and risk ratios were calculated to compare the effect of these therapeutic strategies on overall survival and treatment-related mortality, respectively. Four studies containing 219 patients, with persistent or recurrent esophageal squamous cell carcinoma after dCRT, were included in the meta-analysis. The analysis revealed an overall survival benefit following salvage esophagectomy with a pooled hazard ratio for death of 0.42 (95% confidence interval 0.21-0.86, P = 0.017) compared with second-line CRT. A treatment-related mortality of 10.3% was recorded in the 36 patients who were submitted to salvage esophagectomy, while it was impossible to perform a meta-analysis comparing treatment-related mortality between the groups. Salvage esophagectomy offers significant gain in long-term survival compared with second-line CRT, although the surgery is potentially at a price of a high treatment-related mortality. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
21. EXPOSURE TO DISINFECTION BY-PRODUCTS IN DRINKING WATER DURING PREGNANCY AND CONGENITAL ANOMALIES. A CASE-CONTROL STUDY IN THE EMILIA-ROMAGNA REGION (NORTHERN ITALY)
- Author
-
Elena Righi, Bechtold, P., Mariosa, D., Mastroianni, K., Giacobazzi, P., Predieri, G., Calzolari, E., Astolfi, G., Lauriola, P., Tortorici, D., Fantuzzi, G., and Aggazzotti, G.
- Subjects
trihalomethanes ,chlorite ,congenital anomalies ,disinfection by products ,drinking water disinfection ,chlorate
22. Antidiabetics, statins and the risk of amyotrophic lateral sclerosis
- Author
-
Freya Kamel, Henrik Larsson, Daniela Mariosa, Weimin Ye, Rino Bellocco, Lars-Olof Ronnevi, Catarina Almqvist, Fang Fang, Mariosa, D, Kamel, F, Bellocco, R, Ronnevi, L, Almqvist, C, Larsson, H, Ye, W, and Fang, F
- Subjects
medicine.medical_specialty ,Population ,Type 2 diabetes ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,amyotrophic lateral sclerosi ,030212 general & internal medicine ,Medical prescription ,Amyotrophic lateral sclerosis ,education ,Sweden ,education.field_of_study ,antidiabetic ,business.industry ,Amyotrophic Lateral Sclerosis ,statin ,Odds ratio ,Statin treatment ,medicine.disease ,Confidence interval ,Diabetes Mellitus, Type 2 ,risk factor ,Neurology ,diabete ,Case-Control Studies ,Female ,Neurology (clinical) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,030217 neurology & neurosurgery - Abstract
Background: Medications that are used for treatment of metabolic disorders have been suggested to be associated with the development of amyotrophic lateral sclerosis (ALS). Methods: To examine the associations of antidiabetics and statins with the subsequent risk of ALS we conducted a population-based nested case-control study of 2475 Swedish residents diagnosed with ALS during July 2006 to December 2013 and 12375 population controls (five for each ALS case). We extracted information on filled prescriptions of antidiabetics and statins for both cases and controls from the Swedish Prescribed Drug Register during the years before ALS diagnosis. Conditional logistic regression was used to calculate odds ratios (ORs) for the associations of these medications with ALS risk. Results: Patients with ALS were less likely to have been prescribed with antidiabetics compared with controls [OR, 0.76; 95% confidence intervals (CI), 0.65–0.90]. Conversely, statins were not associated with ALS risk overall (OR, 1.08; 95% CI, 0.98–1.19), although a positive association was noted among women (OR, 1.28; 95% CI, 1.10–1.48). The latter association was mostly explained by ALS cases being more likely to have a first prescription of statins during the year before diagnosis compared with controls (OR, 2.54; 95% CI, 1.84–3.49). Conclusions: The inverse association of antidiabetics with ALS is consistent with the previously reported inverse association between type 2 diabetes and ALS risk. The increase in prescription of statins during the year before ALS diagnosis deserves attention because it might reflect an acceleration of the course of ALS due to statin use.
- Published
- 2020
23. Body Mass Index and Amyotrophic Lateral Sclerosis: A Study of US Military Veterans
- Author
-
John D. Beard, Fang Fang, Silke Schmidt, Freya Kamel, David M. Umbach, Dale P. Sandler, Rino Bellocco, Weimin Ye, Daniela Mariosa, Kelli D. Allen, Jean Keller, Tracy L. Peters, Mariosa, D, Beard, J, Umbach, D, Bellocco, R, Keller, J, Peters, T, Allen, K, Ye, W, Sandler, D, Schmidt, S, Fang, F, and Kamel, F
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Epidemiology ,Original Contributions ,Veterans Health ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Weight Loss ,medicine ,Humans ,ALS, BMI, Epidemiology ,Registries ,Sex Distribution ,Amyotrophic lateral sclerosis ,Survival analysis ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,Amyotrophic Lateral Sclerosis ,Case-control study ,Odds ratio ,Middle Aged ,medicine.disease ,Survival Analysis ,United States ,Confidence interval ,Middle age ,Logistic Models ,030104 developmental biology ,Case-Control Studies ,Physical therapy ,Female ,business ,Body mass index ,030217 neurology & neurosurgery - Abstract
Amyotrophic lateral sclerosis (ALS) may be associated with low body mass index (BMI) at the time of diagnosis. However, the role of premorbid BMI in the development of ALS and survival after diagnosis remains unclear. In 2005–2010, we interviewed 467 patients with ALS from the US National Registry of Veterans with ALS and 975 frequency-matched veteran controls. In this sample, we evaluated the association of BMI and BMI change at different ages with ALS risk using unconditional logistic models and with survival after ALS diagnosis using Cox proportional hazards models. After adjustment for confounders, compared with a moderate increase in BMI between ages 25 and 40 years, stable or decreasing BMI was positively associated with ALS risk (odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.20, 2.16). A 1-unit increase in BMI at age 40 years (OR = 0.95, 95% CI: 0.91, 0.98) but not at age 25 years (OR = 0.99, 95% CI: 0.95, 1.03) was inversely associated with ALS. These associations were similar for bulbar and spinal ALS but stronger for those with a delay of less than 1 year between symptom onset and diagnosis. We found no association between prediagnosis BMI and survival. A decreasing BMI from early to middle age and a low BMI in middle age may be positively associated with ALS risk.
- Published
- 2017
24. Physical activity and body mass index as predictors of prostate cancer risk
- Author
-
Rino Bellocco, Steven N. Blair, Swann Arp Adams, Weimin Ye, Hans-Olov Adami, Alessandra Grotta, Olof Akre, Pär Stattin, Ylva Trolle Lagerros, Daniela Mariosa, Matteo Bottai, Olof Nyrén, Grotta, A, Bottai, M, Adami, H, Adams, S, Akre, O, Blair, S, Mariosa, D, Nyrén, O, Ye, W, Stattin, P, Bellocco, R, and Trolle Lagerros, Y
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Epidemiology ,Urology ,Motor Activity ,Lower risk ,Risk Assessment ,Body Mass Index ,Prostate cancer ,Risk Factors ,Surveys and Questionnaires ,Internal medicine ,medicine ,Humans ,Obesity ,Sweden ,Physical activity ,business.industry ,Incidence ,Incidence (epidemiology) ,Prostatic Neoplasms ,Middle Aged ,medicine.disease ,Cohort ,Cohort study ,business ,Body mass index ,Follow-Up Studies ,Forecasting - Abstract
Purpose: Physical activity and body mass index (BMI) are involved in prostate cancer etiology; possible biologic mechanisms include their effects on hormonal levels. Our aim was to investigate the relationship between physical activity, obesity, and prostate cancer. Methods: We followed a cohort of 13,109 Swedish men for 13 years and investigated the association of self-reported physical activity and BMI at baseline with prostate cancer incidence. We further analyzed whether BMI could modulate effects of physical activity. Occupational, recreational, and total physical activity were analyzed in relation to overall, localized, and advanced prostate cancer. Results: During the study follow-up, we observed a total of 904 cases of prostate cancer (429 localized, 407 advanced, and 68 unclassified). High levels of occupational physical activity were associated with a nonsignificantly decreased risk of overall (HR 0.81, 95 % CI 0.61–1.07), localized (HR 0.75, 95 % CI 0.51–1.12), and advanced (HR 0.85, 95 % CI 0.55–1.31) prostate cancer. We found no association between high BMI and risk of prostate cancer incidence: We observed, however, a significant interaction between BMI and leisure physical activity. Conclusion: No association was confirmed between total physical activity and localized or advanced prostate cancer. The highest, relative to the lowest, level of occupational physical activity tended to be linked to a lower risk of prostate cancer, with a suggested dose–response relationship. We found no association between high BMI and risk of prostate cancer incidence; however, our analyses suggested an interaction between BMI and physical activity during recreational time that merits further investigation in future studies.
- Published
- 2015
25. Cohort profile: The Swedish national march cohort
- Author
-
Daniela Mariosa, Ylva Trolle Lagerros, Weimin Ye, Alessandra Grotta, Hans-Olov Adami, Essi Hantikainen, Rino Bellocco, Francesca Ghilotti, Trolle Lagerros, Y, Hantikainen, E, Mariosa, D, Ye, W, Adami, H, Grotta, A, Ghilotti, F, and Bellocco, R
- Subjects
Gerontology ,Male ,medicine.medical_specialty ,lifestyle ,Health Behavior ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology ,Medicine ,Humans ,Fund raising ,030212 general & internal medicine ,Prospective Studies ,Registries ,Prospective cohort study ,Life Style ,Sweden ,exercise ,business.industry ,Life style ,Retrospective cohort study ,General Medicine ,questionnaires ,Cohort ,Chronic Disease ,Female ,epidemiology ,Health behavior ,business ,030217 neurology & neurosurgery ,Cohort studie ,Cohort study ,Demography - Published
- 2017
26. A prospective cohort study of the combined effects of physical activity and anthropometric measures on the risk of post-menopausal breast cancer
- Author
-
Rino Bellocco, Gaetano Marrone, Olof Nyrén, Hans-Olov Adami, Weimin Ye, Daniela Mariosa, Ylva Trolle Lagerros, Bellocco, R, Marrone, G, Ye, W, Nyrén, O, Adami, H, Mariosa, D, and Lagerros, Y
- Subjects
Adult ,medicine.medical_specialty ,Epidemiology ,Sedentary lifestyle ,Breast Neoplasms ,Motor Activity ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Obesity ,Prospective Studies ,Prospective cohort study ,Exercise ,Proportional Hazards Models ,Sweden ,Proportional hazards model ,business.industry ,Breast neoplasm ,Incidence (epidemiology) ,Incidence ,Hazard ratio ,Middle Aged ,Overweight ,medicine.disease ,Postmenopause ,030220 oncology & carcinogenesis ,Relative risk ,Cohort ,Physical therapy ,Waist circumference ,Female ,Sedentary Behavior ,business ,Follow-Up Studies - Abstract
Although keeping a healthy weight and being physically active are among the few modifiable risk factors for post-menopausal breast cancer, the possible interaction between these two risk factors remains to be established. We analyzed prospectively a cohort of 19,196 women who provided detailed self-report on anthropometric measures, physical activity and possible confounders at enrollment in 1997. We achieved complete follow-up through 2010 and ascertained 609 incident cases of post-menopausal invasive breast cancer. We calculated metabolic energy turnover (MET h/day) per day and fitted Cox proportional hazards models to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs). The incidence of post-menopausal breast cancer among obese women (BMI ≥ 30 kg/m2) was 58 % higher (HR 1.58, CI 1.16–2.16) than in women of normal weight (18.5 ≤ BMI < 25). Women in the lowest tertile of total physical activity (< 31.2 MET h/day) had 40 % higher incidence of post-menopausal breast cancer (HR 1.40, CI 1.11–1.75) than those in the highest tertile (≥ 38.2 MET h/day). The excess incidence linked to these two factors seemed to combine in an approximately additive manner; the incidence among the most obese and sedentary women was doubled (HR 2.07, CI 1.31–3.25) compared with the most physically active women with normal weight. No heterogeneity of the physical activity-linked risk ratios across strata of BMI was detected (p value for interaction = 0.98). This prospective study revealed dose-dependent, homogenous inverse associations between post-menopausal breast cancer incidence and physical activity across all strata of BMI, and between post-menopausal breast cancer incidence and BMI across all strata of physical activity, with no evidence of additive or multiplicative interaction between the two, suggesting independent effects.
- Published
- 2015
27. Dose-response relationship of total and leisure time physical activity to risk of heart failure: a prospective cohort study
- Author
-
Rino Bellocco, Johan Sundström, Olof Nyrén, Erik Ingelsson, Ylva Trolle Lagerros, Claes Held, Weimin Ye, Daniela Mariosa, Hans-Olov Adami, Kasper Andersen, Andersen, K, Mariosa, D, Adami, H, Held, C, Ingelsson, E, Lagerros, Y, Nyrén, O, Ye, W, Bellocco, R, and Sundström, J
- Subjects
Gerontology ,Adult ,Male ,medicine.medical_specialty ,primary prevention ,Motor Activity ,Risk Assessment ,Follow-Up Studie ,Young Adult ,Leisure Activities ,Risk Factors ,Surveys and Questionnaires ,Epidemiology ,Confidence Intervals ,Medicine ,Surveys and Questionnaire ,Humans ,Prospective Studies ,Young adult ,Prospective cohort study ,Exercise ,Life Style ,Aged ,Aged, 80 and over ,Heart Failure ,Sweden ,business.industry ,Incidence (epidemiology) ,Risk Factor ,Medicine (all) ,Incidence ,Middle Aged ,medicine.disease ,Confidence interval ,Prospective Studie ,Heart failure ,Leisure Activitie ,epidemiology ,Female ,Self Report ,Cardiology and Cardiovascular Medicine ,business ,Risk assessment ,Confidence Interval ,Cohort study ,cohort studie ,Human ,Follow-Up Studies - Abstract
Background— The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure. Methods and Results— In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed. Conclusions— Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.
- Published
- 2014
28. Association between diabetes and amyotrophic lateral sclerosis in Sweden
- Author
-
Daniela Mariosa, Weimin Ye, Fang Fang, Freya Kamel, Rino Bellocco, Mariosa, D, Kamel, F, Bellocco, R, Ye, W, and Fang, F
- Subjects
Registrie ,Adult ,Male ,Inverse Association ,medicine.medical_specialty ,Epidemiology ,Population ,Comorbidity ,Diabete ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Motor neuron disease ,Registries ,Amyotrophic lateral sclerosis ,education ,Neurological disorder ,Amyotrophic lateral sclerosi ,Insulin dependence ,Aged ,Aged, 80 and over ,Sweden ,education.field_of_study ,business.industry ,Amyotrophic Lateral Sclerosis ,Case-control study ,Odds ratio ,Neuromuscular disease ,Middle Aged ,medicine.disease ,Diabetes Mellitus, Type 1 ,Neurology ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Physical therapy ,Research method ,Female ,Neurology (clinical) ,Case-Control Studie ,business ,Metabolic and endocrine disorder ,Body mass index ,Human - Abstract
Background and purpose Energy metabolism is altered in patients with amyotrophic lateral sclerosis (ALS) but the role of diabetes is largely unknown. Methods A population-based case−control study was conducted of 5108 ALS cases and 25 540 individually matched population controls during 1991–2010. Information on ALS and pre-existing diabetes was retrieved from the Swedish Patient Register to explore the association of ALS with diabetes overall and with insulin-dependent or non-insulin-dependent diabetes specifically. Variation of the association by diabetes duration and age was also studied. Results In total, 224 ALS cases (4.39%) and 1437 controls (5.63%) had diabetes before the index date, leading to an overall inverse association between diabetes and ALS risk [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.68–0.91]. The association was strong for non-insulin-dependent diabetes (OR 0.66, 95% CI 0.53–0.81) but not for insulin-dependent diabetes (OR 0.83, 95% CI 0.60–1.15) and varied as a function of diabetes duration, with the strongest association observed around 6 years after first ascertainment of diabetes. The association was age-specific; the inverse association was noted only amongst individuals aged 70 or older. In contrast, for younger individuals (
- Published
- 2014
29. Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomization analysis.
- Author
-
Cornish N, Haycock P, Brenner H, Figueiredo JC, Galesloot TE, Grant RC, Johansson M, Mariosa D, McKay J, Pai R, Pellatt AJ, Samadder NJ, Shi J, Thibord F, Trégouët DA, Voegele C, Thirlwell C, Mumford A, and Langdon R
- Subjects
- Humans, Mendelian Randomization Analysis, Genome-Wide Association Study, Risk Factors, Venous Thromboembolism epidemiology, Venous Thromboembolism genetics, Pancreatic Neoplasms epidemiology, Pancreatic Neoplasms genetics
- Abstract
Background: People with cancer experience high rates of venous thromboembolism (VTE). Risk of subsequent cancer is also increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer., Methods: We used data from large genome-wide association study meta-analyses to perform bidirectional Mendelian randomization analyses to estimate causal associations between genetic liability to VTE and risk of 18 different cancers., Results: We found no conclusive evidence that genetic liability to VTE was causally associated with an increased incidence of cancer, or vice versa. We observed an association between liability to VTE and pancreatic cancer risk [odds ratio for pancreatic cancer: 1.23 (95% confidence interval: 1.08-1.40) per log-odds increase in VTE risk, P = 0.002]. However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence to suggest a causal relationship., Conclusions: These findings do not support the hypothesis that genetic liability to VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesize evidence for these mechanisms., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)
- Published
- 2024
- Full Text
- View/download PDF
30. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.
- Author
-
Yarmolinsky J, Robinson JW, Mariosa D, Karhunen V, Huang J, Dimou N, Murphy N, Burrows K, Bouras E, Smith-Byrne K, Lewis SJ, Galesloot TE, Kiemeney LA, Vermeulen S, Martin P, Albanes D, Hou L, Newcomb PA, White E, Wolk A, Wu AH, Le Marchand L, Phipps AI, Buchanan DD, Zhao SS, Gill D, Chanock SJ, Purdue MP, Davey Smith G, Brennan P, Herzig KH, Järvelin MR, Amos CI, Hung RJ, Dehghan A, Johansson M, Gunter MJ, Tsilidis KK, and Martin RM
- Subjects
- Adult, Humans, Mendelian Randomization Analysis, Risk, Inflammation genetics, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Neoplasms epidemiology, Neoplasms genetics
- Abstract
Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear., Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10
-8 ) cis-acting SNPs (i.e., in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r2 < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value ("q-value") <0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q-value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH4 ) >70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis., Findings: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10-1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20-1.69, q-value = 0.055, PPH4 = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53-0.81, q-value = 0.067, PPH4 = 81.8%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR: 0.92, 95% CI: 0.88-0.97, q-value = 0.15, PPH4 = 85.6%). These findings were replicated in pooled analyses with the FinnGen study. Though suggestive evidence was found to support an association of macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR: 2.46, 95% CI: 1.48-4.10, q-value = 0.072, PPH4 = 76.1%), this finding was not replicated when pooled with the FinnGen study. For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk., Interpretation: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated., Funding: Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654)., Competing Interests: Declaration of interests GDS reports Scientific Advisory Board Membership for Relation Therapeutics and Insitro. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
31. Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomisation analysis.
- Author
-
Cornish N, Haycock P, Brenner H, Figueiredo JC, Galesloot T, Grant RC, Johansson M, Mariosa D, McKay J, Pai R, Pellatt AJ, Samadder NJ, Shi J, Thibord F, Trégouët DA, Voegele C, Thirlwell C, Mumford A, and Langdon R
- Abstract
Background: People with cancer experience high rates of venous thromboembolism (VTE). Additionally, risk of subsequent cancer is increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer., Methods: We used data from large genome-wide association study meta-analyses to perform bi-directional Mendelian randomisation analyses to estimate causal associations between genetically-proxied lifetime risk of VTE and risk of 18 different cancers., Results: We found no conclusive evidence that genetically-proxied lifetime risk of VTE was causally associated with an increased incidence of cancer, or vice-versa. We observed an association between VTE and pancreatic cancer risk (odds ratio for pancreatic cancer 1.23 (95% confidence interval 1.08 - 1.40) per log-odds increase in risk of VTE, P = 0.002). However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence from Mendelian randomisation to suggest a causal relationship., Conclusions: These findings do not support the hypothesis that genetically-proxied lifetime risk of VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesise evidence for these mechanisms., Competing Interests: Conflict of interest Robert C Grant is an Advisory or Honoraria for Astrazeneca, Eisai and Knight Therapeutics and is in receipt of a Graduate Scholarship from Pfizer. No other conflicts of interest declared.
- Published
- 2023
- Full Text
- View/download PDF
32. Genetically proxied impaired GIPR signaling and risk of 6 cancers.
- Author
-
Rogers M, Gill D, Ahlqvist E, Robinson T, Mariosa D, Johansson M, Cortez Cardoso Penha R, Dossus L, Gunter MJ, Moreno V, Davey Smith G, Martin RM, and Yarmolinsky J
- Abstract
Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship between GIPR signaling and the risk of cancers influenced by impaired glucose homeostasis is unclear. We examined the association of a variant in GIPR , rs1800437 (E354Q), shown to impair long-term GIPR signaling and lower circulating glucose-dependent insulinotropic peptide concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis (breast, colorectal, endometrial, lung, pancreatic, and renal) in up to 235,698 cases and 333,932 controls. Each copy of E354Q was associated with a higher risk of overall and luminal A-like breast cancer and this association was consistent in replication and colocalization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concentrations. Our human genetics analysis suggests an adverse effect of the GIPR E354Q variant on breast cancer risk, supporting further evaluation of GIPR signaling in breast cancer prevention., Competing Interests: T.R. has received funding from Amgen and Daiichi-Sankyo to attend educational events unrelated to this work. All other authors declare no potential conflicts of interest. All other authors declare no competing interests., (© 2023 The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
33. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.
- Author
-
Yarmolinsky J, Robinson JW, Mariosa D, Karhunen V, Huang J, Dimou N, Murphy N, Burrows K, Bouras E, Smith-Byrne K, Lewis SJ, Galesloot TE, Kiemeney LA, Vermeulen S, Martin P, Albanes D, Hou L, Newcomb PA, White E, Wolk A, Wu AH, Marchand LL, Phipps AI, Buchanan DD, Zhao SS, Gill D, Chanock SJ, Purdue MP, Smith GD, Brennan P, Herzig KH, Jarvelin MR, Dehghan A, Johansson M, Gunter MJ, Tsilidis KK, and Martin RM
- Abstract
Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear., Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis -Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,162 cancer cases and up to 824,556 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant ( P < 5.0 x 10
-8 ) cis -acting SNPs (i.e. in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r2 < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P -value (" q -value") < 0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q -value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH4 ) > 70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes., Results: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR 1.19, 95% CI 1.10-1.29, q -value=0.033, PPH4 =84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR 1.42, 95% CI 1.20-1.69, q -value=0.055, PPH4 =73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR 0.66, 95% CI 0.53-0.81, q -value=0.067, PPH4 =81.8%), macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR 1.14, 95% CI 1.05-1.23, q -value=0.072, PPH4 =76.1%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR 0.92, 95% CI 0.88-0.97, q -value=0.15), PPH4 =85.6%). For 22 of 30 cancer outcomes examined, there was little evidence ( q -value ≥ 0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk., Conclusion: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 5 circulating inflammatory markers in risk of 5 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated.- Published
- 2023
- Full Text
- View/download PDF
34. The association between genetically elevated polyunsaturated fatty acids and risk of cancer.
- Author
-
Haycock PC, Borges MC, Burrows K, Lemaitre RN, Burgess S, Khankari NK, Tsilidis KK, Gaunt TR, Hemani G, Zheng J, Truong T, Birmann BM, OMara T, Spurdle AB, Iles MM, Law MH, Slager SL, Saberi Hosnijeh F, Mariosa D, Cotterchio M, Cerhan JR, Peters U, Enroth S, Gharahkhani P, Le Marchand L, Williams AC, Block RC, Amos CI, Hung RJ, Zheng W, Gunter MJ, Smith GD, Relton C, and Martin RM
- Subjects
- Humans, Fatty Acid Desaturases genetics, Fatty Acid Desaturases metabolism, Fatty Acids, Unsaturated metabolism, Polymorphism, Single Nucleotide, Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms, Fatty Acids, Omega-3, Inflammatory Bowel Diseases, Colorectal Neoplasms
- Abstract
Background: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain., Methods: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures., Findings: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; P
heterogeneity = 0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding., Interpretation: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease., Funding: Cancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973)., Competing Interests: Declaration of interests TRG has received funding from the Medical Research Council, Cancer Research UK and Biogen. BMB has received funding from the US National Institutes of Health/National Cancer Institute, American Institute of Cancer Research and Harvard Chan-NIEHS Center. JRC has received funding from the National Cancer Institute. GDS has received funding from the Medical Research Council. PG has received funding from the National Health and Medical Research Council. RM and PCH have received funding from Cancer Research UK. SB has received funding from the Wellcome Trust and the Medical Research Council. GDS reports Scientific Advisory Board Membership for Relation Therapeutics and Insitro., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
35. Design and quality control of large-scale two-sample Mendelian randomization studies.
- Author
-
Haycock PC, Borges MC, Burrows K, Lemaitre RN, Harrison S, Burgess S, Chang X, Westra J, Khankari NK, Tsilidis KK, Gaunt T, Hemani G, Zheng J, Truong T, O'Mara TA, Spurdle AB, Law MH, Slager SL, Birmann BM, Saberi Hosnijeh F, Mariosa D, Amos CI, Hung RJ, Zheng W, Gunter MJ, Davey Smith G, Relton C, and Martin RM
- Subjects
- Humans, Mendelian Randomization Analysis, Reproducibility of Results, Fatty Acids, Quality Control, Genome-Wide Association Study, Neoplasms epidemiology, Neoplasms genetics
- Abstract
Background: Mendelian randomization (MR) studies are susceptible to metadata errors (e.g. incorrect specification of the effect allele column) and other analytical issues that can introduce substantial bias into analyses. We developed a quality control (QC) pipeline for the Fatty Acids in Cancer Mendelian Randomization Collaboration (FAMRC) that can be used to identify and correct for such errors., Methods: We collated summary association statistics from fatty acid and cancer genome-wide association studies (GWAS) and subjected the collated data to a comprehensive QC pipeline. We identified metadata errors through comparison of study-specific statistics to external reference data sets (the National Human Genome Research Institute-European Bioinformatics Institute GWAS catalogue and 1000 genome super populations) and other analytical issues through comparison of reported to expected genetic effect sizes. Comparisons were based on three sets of genetic variants: (i) GWAS hits for fatty acids, (ii) GWAS hits for cancer and (iii) a 1000 genomes reference set., Results: We collated summary data from 6 fatty acid and 54 cancer GWAS. Metadata errors and analytical issues with the potential to introduce substantial bias were identified in seven studies (11.6%). After resolving metadata errors and analytical issues, we created a data set of 219 842 genetic associations with 90 cancer types, generated in analyses of 566 665 cancer cases and 1 622 374 controls., Conclusions: In this large MR collaboration, 11.6% of included studies were affected by a substantial metadata error or analytical issue. By increasing the integrity of collated summary data prior to their analysis, our protocol can be used to increase the reliability of downstream MR analyses. Our pipeline is available to other researchers via the CheckSumStats package (https://github.com/MRCIEU/CheckSumStats)., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)
- Published
- 2023
- Full Text
- View/download PDF
36. Opioid medications: an emerging cancer risk factor?
- Author
-
Sheikh M, Brennan P, Mariosa D, and Robbins HA
- Subjects
- Humans, Analgesics, Opioid adverse effects, Risk Factors, Opioid-Related Disorders epidemiology, Opioid-Related Disorders drug therapy, Neoplasms drug therapy
- Published
- 2023
- Full Text
- View/download PDF
37. Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study.
- Author
-
Papadimitriou N, Bull CJ, Jenab M, Hughes DJ, Bell JA, Sanderson E, Timpson NJ, Smith GD, Albanes D, Campbell PT, Küry S, Le Marchand L, Ulrich CM, Visvanathan K, Figueiredo JC, Newcomb PA, Pai RK, Peters U, Tsilidis KK, Boer JMA, Vincent EE, Mariosa D, Gunter MJ, Richardson TG, and Murphy N
- Subjects
- Adult, Humans, Child, Middle Aged, Adiposity genetics, Risk Factors, Mendelian Randomization Analysis, Genome-Wide Association Study, Body Mass Index, Polymorphism, Single Nucleotide, Pediatric Obesity, Colonic Neoplasms
- Abstract
Background: Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk., Methods: We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants., Results: Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05)., Conclusions: Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood., (© 2022. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
38. Body Size at Different Ages and Risk of 6 Cancers: A Mendelian Randomization and Prospective Cohort Study.
- Author
-
Mariosa D, Smith-Byrne K, Richardson TG, Ferrari P, Gunter MJ, Papadimitriou N, Murphy N, Christakoudi S, Tsilidis KK, Riboli E, Muller D, Purdue MP, Chanock SJ, Hung RJ, Amos CI, O'Mara TA, Amiano P, Pasanisi F, Rodriguez-Barranco M, Krogh V, Tjønneland A, Halkjær J, Perez-Cornago A, Chirlaque MD, Skeie G, Rylander C, Borch KB, Aune D, Heath AK, Ward HA, Schulze M, Bonet C, Weiderpass E, Davey Smith G, Brennan P, and Johansson M
- Subjects
- Adult, Body Mass Index, Body Size, Cohort Studies, Genome-Wide Association Study, Humans, Obesity complications, Obesity epidemiology, Obesity genetics, Prospective Studies, Mendelian Randomization Analysis, Neoplasms etiology, Neoplasms genetics
- Abstract
It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for 6 obesity-related cancers, we performed univariable and multivariable analyses using 1) Mendelian randomization (MR) analysis and 2) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger early life body size was associated with higher risk of endometrial (odds ratioMR = 1.61, 95% confidence interval = 1.23 to 2.11) and kidney (odds ratioMR = 1.40, 95% confidence interval = 1.09 to 1.80) cancer. These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life body mass index (BMI) was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI., (© World Health Organization, 2022. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)
- Published
- 2022
- Full Text
- View/download PDF
39. The relationship between blood pressure and risk of renal cell carcinoma.
- Author
-
Alcala K, Mariosa D, Smith-Byrne K, Nasrollahzadeh Nesheli D, Carreras-Torres R, Ardanaz Aicua E, Bondonno NP, Bonet C, Brunström M, Bueno-de-Mesquita B, Chirlaque MD, Christakoudi S, Heath AK, Kaaks R, Katzke V, Krogh V, Ljungberg B, Martin RM, May A, Melander O, Palli D, Rodriguez-Barranco M, Sacerdote C, Stocks T, Tjønneland A, Travis RC, Vermeulen R, Chanock S, Purdue M, Weiderpass E, Muller D, Brennan P, and Johansson M
- Subjects
- Blood Pressure, Humans, Prospective Studies, Risk Factors, Carcinoma, Renal Cell epidemiology, Hypertension epidemiology, Kidney Neoplasms epidemiology
- Abstract
Background: The relation between blood pressure and kidney cancer risk is well established but complex and different study designs have reported discrepant findings on the relative importance of diastolic blood pressure (DBP) and systolic blood pressure (SBP). In this study, we sought to describe the temporal relation between diastolic and SBP with renal cell carcinoma (RCC) risk in detail., Methods: Our study involved two prospective cohorts: the European Prospective Investigation into Cancer and Nutrition study and UK Biobank, including >700 000 participants and 1692 incident RCC cases. Risk analyses were conducted using flexible parametric survival models for DBP and SBP both separately as well as with mutuality adjustment and then adjustment for extended risk factors. We also carried out univariable and multivariable Mendelian randomization (MR) analyses (DBP: ninstruments = 251, SBP: ninstruments = 213) to complement the analyses of measured DBP and SBP., Results: In the univariable analysis, we observed clear positive associations with RCC risk for both diastolic and SBP when measured ≥5 years before diagnosis and suggestive evidence for a stronger risk association in the year leading up to diagnosis. In mutually adjusted analysis, the long-term risk association of DBP remained, with a hazard ratio (HR) per standard deviation increment 10 years before diagnosis (HR10y) of 1.20 (95% CI: 1.10-1.30), whereas the association of SBP was attenuated (HR10y: 1.00, 95% CI: 0.91-1.10). In the complementary multivariable MR analysis, we observed an odds ratio for a 1-SD increment (ORsd) of 1.34 (95% CI: 1.08-1.67) for genetically predicted DBP and 0.70 (95% CI: 0.56-0.88) for genetically predicted SBP., Conclusion: The results of this observational and MR study are consistent with an important role of DBP in RCC aetiology. The relation between SBP and RCC risk was less clear but does not appear to be independent of DBP., (© World Health Organization, 2022. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)
- Published
- 2022
- Full Text
- View/download PDF
40. Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer.
- Author
-
Wade KH, Yarmolinsky J, Giovannucci E, Lewis SJ, Millwood IY, Munafò MR, Meddens F, Burrows K, Bell JA, Davies NM, Mariosa D, Kanerva N, Vincent EE, Smith-Byrne K, Guida F, Gunter MJ, Sanderson E, Dudbridge F, Burgess S, Cornelis MC, Richardson TG, Borges MC, Bowden J, Hemani G, Cho Y, Spiller W, Richmond RC, Carter AR, Langdon R, Lawlor DA, Walters RG, Vimaleswaran KS, Anderson A, Sandu MR, Tilling K, Davey Smith G, Martin RM, and Relton CL
- Subjects
- Causality, Humans, Nutritional Status, Risk Factors, Mendelian Randomization Analysis methods, Neoplasms etiology, Neoplasms genetics
- Abstract
Dietary factors are assumed to play an important role in cancer risk, apparent in consensus recommendations for cancer prevention that promote nutritional changes. However, the evidence in this field has been generated predominantly through observational studies, which may result in biased effect estimates because of confounding, exposure misclassification, and reverse causality. With major geographical differences and rapid changes in cancer incidence over time, it is crucial to establish which of the observational associations reflect causality and to identify novel risk factors as these may be modified to prevent the onset of cancer and reduce its progression. Mendelian randomization (MR) uses the special properties of germline genetic variation to strengthen causal inference regarding potentially modifiable exposures and disease risk. MR can be implemented through instrumental variable (IV) analysis and, when robustly performed, is generally less prone to confounding, reverse causation and measurement error than conventional observational methods and has different sources of bias (discussed in detail below). It is increasingly used to facilitate causal inference in epidemiology and provides an opportunity to explore the effects of nutritional exposures on cancer incidence and progression in a cost-effective and timely manner. Here, we introduce the concept of MR and discuss its current application in understanding the impact of nutritional factors (e.g., any measure of diet and nutritional intake, circulating biomarkers, patterns, preference or behaviour) on cancer aetiology and, thus, opportunities for MR to contribute to the development of nutritional recommendations and policies for cancer prevention. We provide applied examples of MR studies examining the role of nutritional factors in cancer to illustrate how this method can be used to help prioritise or deprioritise the evaluation of specific nutritional factors as intervention targets in randomised controlled trials. We describe possible biases when using MR, and methodological developments aimed at investigating and potentially overcoming these biases when present. Lastly, we consider the use of MR in identifying causally relevant nutritional risk factors for various cancers in different regions across the world, given notable geographical differences in some cancers. We also discuss how MR results could be translated into further research and policy. We conclude that findings from MR studies, which corroborate those from other well-conducted studies with different and orthogonal biases, are poised to substantially improve our understanding of nutritional influences on cancer. For such corroboration, there is a requirement for an interdisciplinary and collaborative approach to investigate risk factors for cancer incidence and progression., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
41. Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma.
- Author
-
Riscal R, Bull CJ, Mesaros C, Finan JM, Carens M, Ho ES, Xu JP, Godfrey J, Brennan P, Johansson M, Purdue MP, Chanock SJ, Mariosa D, Timpson NJ, Vincent EE, Keith B, Blair IA, Skuli N, and Simon MC
- Subjects
- Cell Line, Tumor, Cell Proliferation genetics, Cholesterol therapeutic use, Humans, Phosphatidylinositol 3-Kinases metabolism, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology
- Abstract
Clear cell renal cell carcinoma (ccRCC) is characterized by large intracellular lipid droplets containing free and esterified cholesterol; however, the functional significance of cholesterol accumulation in ccRCC cells is unknown. We demonstrate that, surprisingly, genes encoding cholesterol biosynthetic enzymes are repressed in ccRCC, suggesting a dependency on exogenous cholesterol. Mendelian randomization analyses based on 31,000 individuals indicate a causal link between elevated circulating high-density lipoprotein (HDL) cholesterol and ccRCC risk. Depriving ccRCC cells of either cholesterol or HDL compromises proliferation and survival in vitro and tumor growth in vivo; in contrast, elevated dietary cholesterol promotes tumor growth. Scavenger Receptor B1 (SCARB1) is uniquely required for cholesterol import, and inhibiting SCARB1 is sufficient to cause ccRCC cell-cycle arrest, apoptosis, elevated intracellular reactive oxygen species levels, and decreased PI3K/AKT signaling. Collectively, we reveal a cholesterol dependency in ccRCC and implicate SCARB1 as a novel therapeutic target for treating kidney cancer., Significance: We demonstrate that ccRCC cells are auxotrophic for exogenous cholesterol to maintain PI3K/AKT signaling pathway and ROS homeostasis. Blocking cholesterol import through the HDL transporter SCARB1 compromises ccRCC cell survival and tumor growth, suggesting a novel pharmacologic target for this disease. This article is highlighted in the In This Issue feature, p. 2945., (©2021 American Association for Cancer Research.)
- Published
- 2021
- Full Text
- View/download PDF
42. Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer.
- Author
-
Ferreiro-Iglesias A, McKay JD, Brenner N, Virani S, Lesseur C, Gaborieau V, Ness AR, Hung RJ, Liu G, Diergaarde B, Olshan AF, Hayes N, Weissler MC, Schroeder L, Bender N, Pawlita M, Thomas S, Pring M, Dudding T, Kanterewicz B, Ferris R, Thomas S, Brhane Y, Díez-Obrero V, Milojevic M, Smith-Byrne K, Mariosa D, Johansson MJ, Herrero R, Boccia S, Cadoni G, Lacko M, Holcátová I, Ahrens W, Lagiou P, Lagiou A, Polesel J, Simonato L, Merletti F, Healy CM, Hansen BT, Nygård M, Conway DI, Wright S, Macfarlane TV, Robinson M, Alemany L, Agudo A, Znaor A, Amos CI, Waterboer T, and Brennan P
- Subjects
- Aged, Antibodies, Viral biosynthesis, Capsid Proteins genetics, Capsid Proteins immunology, Case-Control Studies, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA Antigens classification, HLA Antigens genetics, Haplotypes, Human papillomavirus 16 pathogenicity, Humans, Male, Meta-Analysis as Topic, Middle Aged, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Mouth Neoplasms virology, Oncogene Proteins, Viral genetics, Oncogene Proteins, Viral immunology, Oropharyngeal Neoplasms genetics, Oropharyngeal Neoplasms pathology, Oropharyngeal Neoplasms virology, Papillomavirus Infections genetics, Papillomavirus Infections pathology, Papillomavirus Infections virology, Quantitative Trait Loci, Repressor Proteins genetics, Repressor Proteins immunology, Risk Factors, Smoking physiopathology, HLA Antigens immunology, Human papillomavirus 16 immunology, Immunity, Humoral, Mouth Neoplasms immunology, Oropharyngeal Neoplasms immunology, Papillomavirus Infections immunology
- Abstract
Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
43. Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study.
- Author
-
Dimou NL, Papadimitriou N, Mariosa D, Johansson M, Brennan P, Peters U, Chanock SJ, Purdue M, Bishop DT, Gago-Dominquez M, Giles GG, Moreno V, Platz EA, Tangen CM, Wolk A, Zheng W, Wu X, Campbell PT, Giovannucci E, Lin Y, Gunter MJ, and Murphy N
- Subjects
- Adiponectin blood, Adiponectin genetics, Body Mass Index, Carcinoma, Renal Cell complications, Colorectal Neoplasms complications, Correlation of Data, Endometrial Neoplasms complications, Female, Genome-Wide Association Study, Humans, Leptin blood, Leptin genetics, Mendelian Randomization Analysis, Ovarian Neoplasms complications, Pancreatic Neoplasms complications, Plasminogen Activator Inhibitor 1 blood, Plasminogen Activator Inhibitor 1 genetics, Principal Component Analysis, Receptors, Leptin blood, Receptors, Leptin genetics, Risk Factors, Adipokines blood, Adipokines genetics, Carcinoma, Renal Cell genetics, Colorectal Neoplasms genetics, Endometrial Neoplasms genetics, Obesity complications, Ovarian Neoplasms genetics, Pancreatic Neoplasms genetics
- Abstract
Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines (adiponectin, leptin, soluble leptin receptor [sOB-R] and plasminogen activator inhibitor-1 [PAI-1]) with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma [RCC], ovarian and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin and 4 for both sOB-R and PAI-1 (P value for inclusion<5 × 10
-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer (odds ratio per 1 μg/mL increment in adiponectin concentration: 0.90 [95% confidence interval = 0.84-0.97]; P = .01); but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, RCC, ovarian cancer and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R and PAI-1 concentrations on the development of five obesity-related cancers., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)- Published
- 2021
- Full Text
- View/download PDF
44. Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study.
- Author
-
Seyed Khoei N, Carreras-Torres R, Murphy N, Gunter MJ, Brennan P, Smith-Byrne K, Mariosa D, Mckay J, O'Mara TA, Jarrett R, Hjalgrim H, Smedby KE, Cozen W, Onel K, Diepstra A, Wagner KH, and Freisling H
- Subjects
- Biomarkers analysis, Breast Neoplasms drug therapy, Genome-Wide Association Study, Humans, Risk Factors, Bilirubin genetics, Breast Neoplasms genetics, Mendelian Randomization Analysis methods, Polymorphism, Single Nucleotide genetics
- Abstract
Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin's lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin's lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated ( p < 5 × 10
-8 ) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 ( UGT1A1) gene explained 16.9% and the remaining 114 SNPs (non- UGT1A1 SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non- UGT1A1 SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin's lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73-0.99, P 0.04 and OR 0.64, 95% CI 0.42-0.99, p 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04-1.20, p 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin's lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers.- Published
- 2021
- Full Text
- View/download PDF
45. The role of genomics in global cancer prevention.
- Author
-
Ginsburg O, Ashton-Prolla P, Cantor A, Mariosa D, and Brennan P
- Subjects
- Brazil, Cost-Benefit Analysis, Founder Effect, Genetic Predisposition to Disease, Genomics economics, Germ-Line Mutation, Humans, Mendelian Randomization Analysis, Mutation, Neoplasms epidemiology, United States, Genomics methods, Neoplasms genetics, Neoplasms prevention & control
- Abstract
Despite improvements in the understanding of cancer causation, much remains unknown regarding the mechanisms by which genomic and non-genomic factors initiate carcinogenesis, drive cell invasion and metastasis, and enable cancer to develop. Technological advances have enabled the analysis of whole genomes, comprising thousands of tumours across populations worldwide, with the aim of identifying mutation signatures associated with particular tumour types. Large collaborative efforts have resulted in the identification and improved understanding of causal factors, and have shed light on new opportunities to prevent cancer. In this new era in cancer genomics, discoveries from studies conducted on an international scale can inform evidence-based strategies in cancer control along the cancer care continuum, from prevention to treatment. In this Review, we present the relevant history and emerging frontiers of cancer genetics and genomics from the perspective of global cancer prevention. We highlight the importance of local context in the adoption of new technologies and emergent evidence, with illustrative examples from worldwide. We emphasize the challenges in implementing important genomic findings in clinical settings with disparate resource availability and present a conceptual framework for the translation of such findings into clinical practice, and evidence-based policies in order to maximize the utility for a population.
- Published
- 2021
- Full Text
- View/download PDF
46. Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow-up.
- Author
-
Yazdani S, Mariosa D, Hammar N, Andersson J, Ingre C, Walldius G, and Fang F
- Subjects
- Aged, Amyotrophic Lateral Sclerosis epidemiology, Biomarkers blood, Cohort Studies, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Neurodegenerative Diseases blood, Neurodegenerative Diseases epidemiology, Neurodegenerative Diseases immunology, Parkinson Disease epidemiology, Prospective Studies, Sweden epidemiology, Time Factors, Amyotrophic Lateral Sclerosis blood, Amyotrophic Lateral Sclerosis immunology, Immunity, Cellular immunology, Parkinson Disease blood, Parkinson Disease immunology
- Abstract
Objective: To assess the associations of several blood immune biomarkers with the future risks of amyotrophic lateral sclerosis and Parkinson disease in a prospective cohort study with 20 years of follow-up., Methods: The Swedish Apolipoprotein-Related Mortality Risk study is a longitudinal cohort study including 812,073 participants with repeated blood biomarker measurements between 1985 and 1996 and a follow-up until 2011. Using a Cox model, we first estimated hazard ratios of amyotrophic lateral sclerosis and Parkinson disease in relation to leukocytes, immunoglobulin G, haptoglobin, and uric acid. We further described the temporal changes of these biomarkers during the 20 years prior to the diagnosis of these diseases., Results: A total of 585 incident cases of amyotrophic lateral sclerosis and 3,769 incident cases of Parkinson disease were identified during the follow-up. Increasing concentrations of leukocytes, haptoglobin, and uric acid were associated with a lower risk of Parkinson disease. No statistically significant association was, however, noted between the studied biomarkers and amyotrophic lateral sclerosis. Parkinson disease patients appeared to have lower levels of leukocytes and haptoglobin between 20 and 10 years before diagnosis and lower levels of uric acid during the 20 years before diagnosis, compared to controls, although statistically significant differences were only noted during parts of the respective time intervals after multivariable adjustment. No clear differences were noted between patients with amyotrophic lateral sclerosis and controls., Interpretation: If verified in studies of independent populations, our findings may suggest a different role of systemic inflammation on the risk of Parkinson disease compared to amyotrophic lateral sclerosis. ANN NEUROL 2019;86:913-926., (© 2019 American Neurological Association.)
- Published
- 2019
- Full Text
- View/download PDF
47. Lipids, Apolipoproteins, and the Risk of Parkinson Disease.
- Author
-
Fang F, Zhan Y, Hammar N, Shen X, Wirdefeldt K, Walldius G, and Mariosa D
- Subjects
- Adult, Case-Control Studies, Cohort Studies, Female, Humans, Lipids blood, Lipids genetics, Male, Middle Aged, Parkinson Disease epidemiology, Prospective Studies, Risk Factors, Sweden epidemiology, Apolipoproteins blood, Apolipoproteins genetics, Mendelian Randomization Analysis methods, Parkinson Disease blood, Parkinson Disease genetics
- Abstract
Rationale: A complete picture of the associations of the most common lipid fractions, including total cholesterol (TC), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), triglycerides, and apolipoproteins, with the risk of Parkinson disease (PD), is lacking., Objective: To assess the associations of lipids and apolipoproteins with the future risk of PD., Methods and Results: In the AMORIS (Apolipoprotein-Related Mortality Risk) Study, we enrolled ≈600 000 participants during 1985 to 1996 in Stockholm, Sweden, with repeated measurements of TC, LDL-C, HDL-C, triglycerides, ApoB (apolipoprotein B), and ApoA-I (apolipoprotein A-I). The cohort was followed until the end of 2011, and incident cases of PD were identified through the Swedish Patient Register. We first used Cox models to estimate the associations of these biomarkers with later risk of PD. We further applied a Mendelian randomization analysis for TC, LDL-C, and triglycerides using the GWAS (Genome-wide association study) summary statistics from the public PD GWAS data and 23andMe PD cohorts with >800 000 individuals. One SD increase of TC was associated with a lower hazard of PD (hazard ratio, 0.90; 95% CI, 0.87-0.94). Similar associations were observed for LDL-C (hazard ratio, 0.93; 95% CI, 0.88-0.98), triglycerides (hazard ratio, 0.94; 95% CI, 0.90-0.97), and ApoB (hazard ratio, 0.91; 95% CI, 0.85-0.97). A clear dose-response relation was also noted when using these biomarkers as categorical variables. A causal inverse association of TC, LDL-C, and triglycerides with PD risk was further suggested by the Mendelian randomization analysis., Conclusions: Our findings reinforce that higher levels of TC, LDL-C, and triglycerides are associated with a lower future risk of PD and further suggest that these associations may be causal. The findings for ApoB in relation to PD risk are novel, and whether such association is causal needs to be examined.
- Published
- 2019
- Full Text
- View/download PDF
48. Commentary: What can Mendelian randomization tell us about causes of cancer?
- Author
-
Mariosa D, Carreras-Torres R, Martin RM, Johansson M, and Brennan P
- Subjects
- Biological Specimen Banks, Humans, Overweight epidemiology, United Kingdom epidemiology, Causality, Mendelian Randomization Analysis, Neoplasms epidemiology, Obesity epidemiology
- Published
- 2019
- Full Text
- View/download PDF
49. The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.
- Author
-
Johansson M, Carreras-Torres R, Scelo G, Purdue MP, Mariosa D, Muller DC, Timpson NJ, Haycock PC, Brown KM, Wang Z, Ye Y, Hofmann JN, Foll M, Gaborieau V, Machiela MJ, Colli LM, Li P, Garnier JG, Blanche H, Boland A, Burdette L, Prokhortchouk E, Skryabin KG, Yeager M, Radojevic-Skodric S, Ognjanovic S, Foretova L, Holcatova I, Janout V, Mates D, Mukeriya A, Rascu S, Zaridze D, Bencko V, Cybulski C, Fabianova E, Jinga V, Lissowska J, Lubinski J, Navratilova M, Rudnai P, Benhamou S, Cancel-Tassin G, Cussenot O, Weiderpass E, Ljungberg B, Tumkur Sitaram R, Häggström C, Bruinsma F, Jordan SJ, Severi G, Winship I, Hveem K, Vatten LJ, Fletcher T, Larsson SC, Wolk A, Banks RE, Selby PJ, Easton DF, Andreotti G, Beane Freeman LE, Koutros S, Männistö S, Weinstein S, Clark PE, Edwards TL, Lipworth L, Gapstur SM, Stevens VL, Carol H, Freedman ML, Pomerantz MM, Cho E, Wilson KM, Gaziano JM, Sesso HD, Freedman ND, Parker AS, Eckel-Passow JE, Huang WY, Kahnoski RJ, Lane BR, Noyes SL, Petillo D, Teh BT, Peters U, White E, Anderson GL, Johnson L, Luo J, Buring J, Lee IM, Chow WH, Moore LE, Eisen T, Henrion M, Larkin J, Barman P, Leibovich BC, Choueiri TK, Lathrop GM, Deleuze JF, Gunter M, McKay JD, Wu X, Houlston RS, Chanock SJ, Relton C, Richards JB, Martin RM, Davey Smith G, and Brennan P
- Subjects
- Blood Glucose analysis, Blood Pressure, Body Mass Index, Carcinoma, Renal Cell genetics, Diabetes Mellitus, Type 2 complications, Female, Genetic Markers, Genome-Wide Association Study, Humans, Insulin blood, Kidney Neoplasms genetics, Lipids blood, Male, Mendelian Randomization Analysis, Obesity genetics, Risk Factors, Carcinoma, Renal Cell etiology, Kidney Neoplasms etiology, Obesity complications
- 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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: TE declared employment, research support, and stock in AstraZeneca and research support from Bayer and Pfizer. PCH is a population health fellow of Cancer Research UK. GDS is a member of the Editorial Board of PLOS Medicine.
- Published
- 2019
- Full Text
- View/download PDF
50. Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis.
- Author
-
Fang F, Peters TL, Beard JD, Umbach DM, Keller J, Mariosa D, Allen KD, Ye W, Sandler DP, Schmidt S, and Kamel F
- Subjects
- Adult, Age Distribution, Age of Onset, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis blood, Amyotrophic Lateral Sclerosis mortality, Biomarkers blood, Disease Progression, Female, Humans, Male, Middle Aged, Peptides blood, Proportional Hazards Models, Registries, Risk Assessment, Sex Distribution, Survival Analysis, United States epidemiology, Amyotrophic Lateral Sclerosis etiology, Bone Remodeling, Collagen Type I blood, Lead blood, Veterans Health statistics & numerical data
- Abstract
Blood lead and bone turnover may be associated with the risk of amyotrophic lateral sclerosis (ALS). We aimed to assess whether these factors were also associated with time from ALS diagnosis to death through a survival analysis of 145 ALS patients enrolled during 2007 in the National Registry of Veterans with ALS. Associations of survival time with blood lead and plasma biomarkers of bone resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay, site of onset, and score on the Revised ALS Functional Rating Scale. Hazard ratios were calculated for each doubling of biomarker concentration. Blood lead, plasma CTX, and plasma PINP were mutually adjusted for one another. Increased lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival, whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42, 0.83), after ALS diagnosis. No interactions were observed between lead or bone turnover and other prognostic indicators. Lead toxicity and bone metabolism may be involved in ALS pathophysiology., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.