| 1. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 2. |
- de Gonzalez, Amy Berrington, et al.
(författare)
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Body-Mass Index and Mortality among 1.46 Million White Adults.
- 2010
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 363:23, s. 2211-2219
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. Methods: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). Results: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. Conclusions: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9. N Engl J Med 2010;363:2211-9.
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| 3. |
- Dorans, Kirsten S., et al.
(författare)
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Alcohol and Incident Heart Failure Among Middle-Aged and Elderly Men Cohort of Swedish Men
- 2015
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Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 8:3, s. 422-427
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Tidskriftsartikel (refereegranskat)abstract
- Background Compared with no alcohol consumption, heavy alcohol intake is associated with a higher rate of heart failure (HF) whereas light-to-moderate intake may be associated with a lower rate. However, several prior studies did not exclude former drinkers, who may have changed alcohol consumption in response to diagnosis. This study aimed to investigate the association between alcohol intake and incident HF. Methods and Results We conducted a prospective cohort study of 33 760 men aged 45 to 79 years with no HF, diabetes mellitus, or myocardial infarction at baseline participating in the Cohort of Swedish Men Study. We excluded former drinkers. At baseline, participants completed a food frequency questionnaire and reported other characteristics. HF was defined as hospitalization for or death from HF, ascertained by Swedish inpatient and cause-of-death records from January 1, 1998, through December 31, 2011. We constructed Cox proportional hazards models to estimate multivariable-adjusted incidence rate ratios. During follow-up, 2916 men were hospitalized for (n=2139) or died (n=777) of incident HF. There was a U-shaped relationship between total alcohol intake and incident HF (P=0.0004). There was a nadir at light-to-moderate alcohol intake: consuming 7 to <14 standard drinks per week was associated with a 19% lower multivariable-adjusted rate of HF compared with never drinking (incidence rate ratio, 0.81; 95% confidence interval, 0.69-0.96). Conclusions In this cohort of Swedish men, there was a U-shaped relationship between alcohol consumption and HF incidence, with a nadir at light-to-moderate intake. Heavy intake did not seem protective.
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| 4. |
- Escala-Garcia, Maria, et al.
(författare)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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| 5. |
- Gaudet, Mia M., et al.
(författare)
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Anthropometry and head and neck cancer : a pooled analysis of cohort data
- 2015
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Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 44:2, s. 673-681
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Tidskriftsartikel (refereegranskat)abstract
- Background: Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed to evaluate these associations while minimizing biases found in previous studies. Methods: We pooled data from 1 941 300 participants, including 3760 cases, in 20 cohort studies and used multivariable-adjusted Cox proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of anthropometric measures with HNC risk overall and stratified by smoking status. Results: Greater waist circumference (per 5cm: HR = 1.04, 95% CI 1.03-1.05, P-value for trend = <0.0001) and waist-to-hip ratio (per 0.1 unit: HR = 1.07, 95% CI 1.05-1.09, P-value for trend = <0.0001), adjusted for body mass index (BMI), were associated with higher risk and did not vary by smoking status (P-value for heterogeneity = 0.85 and 0.44, respectively). Associations with BMI (P-value for interaction = <0.0001) varied by smoking status. Larger BMI was associated with higher HNC risk in never smokers (per 5 kg/m(2): HR = 1.15, 95% CI 1.06-1.24, P-value for trend = 0.0006), but not in former smokers (per 5 kg/m(2): HR = 0.99, 95% CI 0.93-1.06, P-value for trend = 0.79) or current smokers (per 5 kg/m(2): HR = 0.76, 95% CI 0.71-0.82, P-value for trend = <0.0001). Larger hip circumference was not associated with a higher HNC risk. Greater height (per 5cm) was associated with higher risk of HNC in never and former smokers, but not in current smokers. Conclusions: Waist circumference and waist-to-hip ratio were associated positively with HNC risk regardless of smoking status, whereas a positive association with BMI was only found in never smokers.
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| 6. |
- Khalili, Hamed, et al.
(författare)
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Diet Quality and Risk of Older-Onset Crohn's Disease and Ulcerative Colitis
- 2023
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:5, s. 746-753
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To assess the relationship between diet quality and risk of older-onset Crohn's disease (CD) and ulcerative colitis (UC).METHODS: We conducted a prospective cohort study of 83,147 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men. We used food frequency questionnaire to calculate adherence scores to multiple derived health diet patterns: Alternate Healthy Eating Index (AHEI), Healthy Eating Index-2015 (HEI-2015), Healthful Plant-Based Diet Index (HPDI), and modified Mediterranean Diet Score (mMED) at baseline in 1997 in both cohorts. Diagnoses of CD and UC were retrieved from the Swedish Patient Register. We used Cox proportional hazards modeling to estimate the adjusted hazard ratios (HRs) and 95% CIs.FINDINGS: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC. Comparing the highest to the lowest quartiles, the adjusted HRs of CD were 0.73 (95% CI, 0.48, 1.12, Ptrend = 0.123) for AHEI; 0.90 (0.57, 1.41, Ptrend = 0.736) for HEI 2015; 0.52 (95% CI 0.32, 0.85, Ptrend = 0.011) for HPDI; and 0.58 (95% CI 0.32, 1.06, Ptrend = 0.044) for mMED. In contrast, we did not observe an association between any diet quality score and risk of UC.INTERPRETATION: We found that several healthy eating patterns were associated with a lower risk of older-onset CD. Our findings provide a rationale for adapting different healthy dietary patterns based on individuals' food preferences and traditions for designing future prevention strategies for IBD.
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| 7. |
- Kitahara, Cari M., et al.
(författare)
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Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype : Pooled Analysis of 22 Prospective Studies
- 2016
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Ingår i: Thyroid. - : MARY ANN LIEBERT, INC. - 1050-7256 .- 1557-9077. ; 26:2, s. 306-318
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Tidskriftsartikel (refereegranskat)abstract
- Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5cm)=1.07 [1.04-1.10], BMI (per 5kg/m(2))=1.06 [1.02-1.10], waist circumference (per 5cm)=1.03 [1.01-1.05], young-adult BMI (per 5kg/m(2))=1.13 [1.02-1.25], and adulthood BMI gain (per 5kg/m(2))=1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p=0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.
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| 8. |
- Lin, Yulan, et al.
(författare)
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Dietary Intake of Lignans and Risk of Esophageal and Gastric Adenocarcinoma : A Cohort Study in Sweden
- 2013
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 22:2, s. 308-312
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Tidskriftsartikel (refereegranskat)abstract
- High intake of phytoestrogen lignans has been found to be associated with decreased risk of esophageal adenocarcinoma in our previous population-based case-control study in Sweden. To further evaluate this possible association, we tested the hypothesis of an inverse association between dietary lignan intake and risk of esophageal and gastric adenocarcinoma using a prospective design. In a population-based cohort study in Sweden, 81,670 participants who were cancer-free at baseline were followed up during 1998 to 2009. All participants completed a 96-item food frequency questionnaire (FFQ), which was used to assess dietary exposure to lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol, and syringaresinol). All cases of esophageal, gastroesophageal junctional, and gastric adenocarcinoma were identified through linkage to the Swedish Cancer Register. Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI), with adjustment for potential confounding factors. During an average follow-up of 9.9 years, a total of 211 cases were identified, including 83 cases of esophageal or junctional adenocarcinoma, and 128 cases of gastric adenocarcinoma. There was no statistically significant association between dietary intake of lignans and any of the studied adenocarcinomas. Compared with participants in the lowest quartile of lignan intake, the adjusted HR of the highest quartile was 0.96 (95% CI, 0.46-2.00; P-trend = 0.70) for adenocarcinoma of the esophagus or gastroesophageal junction, and 0.89 (95% CI, 0.52-1.55: P-trend = 0.78) for gastric adenocarcinoma. No clear support for a protective role of dietary intake of lignans in the development of esophageal or gastric adenocarcinoma was found. Cancer Epidemiol Biomarkers Prev; 22(2); 308-12. (c) 2012 AACR.
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| 9. |
- Lin, Yulan, et al.
(författare)
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Validation of FFQ-based assessment of dietary lignans compared with serum enterolactone in Swedish women
- 2013
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Ingår i: British Journal of Nutrition. - : CAMBRIDGE UNIV PRESS. - 0007-1145 .- 1475-2662. ; 109:10, s. 1873-1880
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Tidskriftsartikel (refereegranskat)abstract
- The validity of using FFQ to assess dietary lignans is uncertain. We aimed to validate the use of FFQ for the assessment of dietary intake of lignans compared to the serum biomarker enterolactone, the main product of dietary lignans' metabolism in human subjects. A random sample of women, aged 55-75 years, from the Swedish Mammography Cohort was selected. Information from two FFQ, the FFQ-87 (sixty-seven food items) and the FFQ-97 (ninety-three food items), and blood samples were collected. Dietary intake of lignans (secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol and syringaresinol) was assessed by the FFQ. Serum concentrations of enterolactone were analysed by time-resolved fluoroimmunoassay. The correlation coefficient between energy-adjusted lignan intake and serum enterolactone was estimated in crude and multivariable-adjusted models, taking into account the factors potentially influencing the serum enterolactone. Among the 135 participants aged 55-75 years, with a mean BMI of 26.7 kg/m(2), the average energy-adjusted intake of total lignans was 1616 (SD 424) and 1516 (SD 409) mu g/d according to the FFQ-87 (forty-five food items containing lignans) and the FFQ-97 (sixty-five food items containing lignans), respectively. The mean concentration of serum enterolactone was 23.2 (SD 15.4) nmol/l. The adjusted Pearson's correlation between dietary intake of lignans assessed by the FFQ-97 and serum enterolactone was statistically significant (r 0.22, P=0.01). No significant correlation was observed for the FFQ-87 (r 0.09, P=0.30). The present study indicates that the FFQ-97 might be better than the FFQ-87 for assessing dietary intake of lignans, although the correlation was low.
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| 10. |
- Mueller, Stefanie H., et al.
(författare)
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Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
- 2023
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Ingår i: Genome Medicine. - : BioMed Central (BMC). - 1756-994X .- 1756-994X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
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