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1.
Int J Cancer ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427315

RESUMO

Toxoplasma gondii (T gondii) is a common parasite that shows affinity to neural tissue and may lead to the formation of cysts in the brain. Previous epidemiologic studies have suggested an association between glioma and increased prevalence of T gondii infection, but prospective studies are lacking. Therefore, we examined the association between prediagnostic T gondii antibodies and risk of glioma in two prospective cohorts using a nested case-control study design. Cases and matched controls were selected from the American Cancer Society's Cancer Prevention Study-II Nutrition Cohort (CPSII-NC) (n = 37 cases and 74 controls) and the Norwegian Cancer Registry's Janus Serum Bank (Janus) (n = 323 cases and 323 controls). Blood samples collected prior to diagnosis were analyzed for antibodies to two T gondii surface antigens (p22 and sag-1), with individuals considered seropositive if antibodies to either antigen were detected. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for each cohort. In both cohorts, a suggestive increase in glioma risk was observed among those infected with T gondii (OR: 2.70; 95% CI: 0.96-7.62 for CPSII-NC; OR: 1.32, 95% CI: 0.85-2.07 for Janus), particularly among participants with high antibody titers specific to the sag-1 antigen (CPSII-NC OR: 3.35, 95% CI: 0.99-11.38; Janus OR: 1.79, 95% CI: 1.02-3.14). Our findings provide the first prospective evidence of an association between T gondii infection and risk of glioma. Further studies with larger case numbers are needed to confirm a potential etiologic role for T gondii in glioma.

2.
Microorganisms ; 8(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143263

RESUMO

Previously, we found that risk of colorectal cancer (CRC) is increased in individuals with serum antibody response to both Helicobacter pylori (HP) Vacuolating Cytotoxin (VacA) toxin or Streptococcus gallolyticus (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts. To examine whether combined SGG Gallo2178 and HP VacA sero-status was associated with CRC risk, we used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to dual sero-negative individuals, there was no increased risk for individuals sero-positive to SGG Gallo2178 only (OR: 0.93; 95% CI: 0.66-1.31) or to HP VacA only (OR: 1.08; 95% CI: 0.98-1.19). However, dual sero-positive individuals had a >50% increased odds of developing CRC (OR: 1.54; 95% CI: 1.16-2.04), suggesting an interaction between antibody responses to these two pathogens and CRC risk (pinteraction = 0.06). In conclusion, this study suggests that dual sero-positivity to HP VacA and SGG Gallo2178 is an indicator of increased risk of CRC.

3.
Eur J Epidemiol ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33128203

RESUMO

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.

4.
Prev Chronic Dis ; 17: E78, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762807

RESUMO

INTRODUCTION: Muscle-strengthening activity (MSA) has beneficial effects on hypertension, glucose homeostasis, and other health conditions; however, its association with mortality is not as well understood. METHODS: We analyzed data from the Cancer Prevention Study-II Nutrition Cohort (data collection 1982-2014), a prospective US cohort that consisted of 72,462 men and women who were free of major chronic diseases; 18,034 of the cohort died during 13 years of follow-up (2001-2014). We used Cox proportional hazards modeling, controlling for various potential confounding factors, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for MSA (none, >0 to <1 h/wk, 1 to <2 h/wk, and ≥2 h/wk) in relation to mortality risk, independent of and in combination with aerobic physical activity. RESULTS: The association between MSA and mortality appeared to be nonlinear (quadratic trend P value, <.001). After multivariable adjustment and comparison with no MSA, engaging in less than 2 hours per week of MSA was associated with lowered all-cause mortality (>0 to <1 h/wk: HR = 0.88, 95% CI, 0.82-0.94; 1 to <2 h/wk: HR = 0.90, 95% CI, 0.84-0.97), but engaging in 2 or more hours per week was not associated with reduced risk (HR = 1.01; 95% CI, 0.92-1.09). Associations were similar but not significant for cancer mortality. Engaging in >0 to <1 hr/wk of MSA was associated with a 19% lower risk (HR = 0.81; 95% CI, 0.71-0.92) of cardiovascular disease mortality, but more time spent in MSA was not associated with reduced risk (quadratic trend P value =.005). Associations did not vary by amount of moderate-to-vigorous aerobic physical activity. CONCLUSION: Engaging in ≥2 hours per week of MSA was associated with lower all-cause mortality, independent of aerobic activity. Reasons for the lack of association with higher amounts of MSA are unclear. Our findings support recommending muscle-strengthening activities for overall health.

5.
Int J Cancer ; 147(11): 3110-3118, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32506449

RESUMO

Cadmium and lead are persistent environmental toxins that are known or probable carcinogens, based on evidence for causality for nonhematologic cancers. Associations of these metals with risk of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are unknown but biologically plausible. To examine the associations of circulating levels of lead and cadmium exposure with risk of B-cell NHL (B-NHL) and multiple myeloma, we conducted a nested case-control study among 299 incident B-cell NHLs and 76 MM cases within the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). Each case was incidence-density matched to two eligible controls on age, race, sex and blood draw date. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for lymphoid malignancies overall and stratified by subtype. We observed a significant positive association between high erythrocyte lead concentration and risk of lymphoid malignancies overall (RR = 1.16, 95% CI: 1.02-1.33 per 17.6 µg/L (1 standard deviation [SD])) and follicular lymphoma in particular (RR = 1.80, 95% CI: 1.15-2.80 per SD). In contrast, there was no association between erythrocyte cadmium and risk of B-NHL (RR = 0.89, 95% CI: 0.75-1.06 per 0.37 µg/L [1 SD]), or any B-NHL subtypes; but a strong inverse association with MM risk (RR = 0.59, 95% CI: 0.38-0.89, per SD). Results from our study suggest a positive association between erythrocyte lead level and risk of lymphoid malignancies and a possible inverse association between cadmium and myeloma. Additional research is needed to confirm and further explore these findings.

6.
J Cancer Surviv ; 14(4): 518-526, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32166577

RESUMO

PURPOSE: Survivors of multiple primary cancers make up a sizable proportion of all cancer survivors, yet little is known about the health of this population. We examined the prevalence of medical conditions and physical function deficits among multiple primary survivors compared with single primary survivors and individuals without a cancer history. METHODS: Participants were enrolled in the Cancer Prevention Study (CPS)-II Nutrition Cohort in 1992/1993. Prevalent medical conditions (diabetes, heart conditions, cerebrovascular conditions, emphysema/chronic bronchitis, osteoporosis, osteoarthritis), physical function limitations, use of a cane or walker, balance difficulties, and falls within the past year were assessed on a follow-up survey completed in 2011. We estimated age- and sex-adjusted prevalence ratios (PRs), comparing multiple primary survivors (N = 1003) to single primary survivors (N = 12,849) and participants without cancer (N = 63,578). RESULTS: The prevalence of medical conditions did not differ substantially between multiple primary survivors and either comparison group. However, multiple primary survivors were more likely to report severe limitations in physical function than the single primary (PR = 1.48 (95% CI, 1.28-1.71)) and no-cancer (PR = 1.64 (95% CI, 1.42-1.88)) groups. Using a cane or walker and balance difficulties were also significantly more common among multiple primary survivors. CONCLUSIONS: Despite a similar prevalence of comorbid medical conditions, severe functional limitations were significantly more common among multiple primary survivors than single primary survivors or individuals without cancer. IMPLICATIONS FOR CANCER SURVIVORS: Assessment of functional status and treatment of physical deficits may be an especially critical component of care for older patients with a history of multiple cancer diagnoses.

7.
Am J Hum Genet ; 106(2): 264-271, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32004448

RESUMO

Severe aplastic anemia (SAA) is a rare disorder characterized by hypoplastic bone marrow and progressive pancytopenia. The etiology of acquired SAA is not understood but is likely related to abnormal immune responses and environmental exposures. We conducted a genome-wide association study of individuals with SAA genetically matched to healthy controls in discovery (359 cases, 1,396 controls) and validation sets (175 cases, 1,059 controls). Combined analyses identified linked SNPs in distinct blocks within the major histocompatibility complex on 6p21. The top SNP encodes p.Met76Val in the P4 binding pocket of the HLA class II gene HLA-DPB1 (rs1042151A>G, odds ratio [OR] 1.75, 95% confidence interval [CI] 1.50-2.03, p = 1.94 × 10-13) and was associated with HLA-DP cell surface expression in healthy individuals (p = 2.04 × 10-6). Phylogenetic analyses indicate that Val76 is not monophyletic and likely occurs in conjunction with different HLA-DP binding groove conformations. Imputation of HLA-DPB1 alleles revealed increased risk of SAA associated with Val76-encoding alleles DPB1∗03:01, (OR 1.66, p = 1.52 × 10-7), DPB1∗10:01 (OR 2.12, p = 0.0003), and DPB1∗01:01 (OR 1.60, p = 0.0008). A second SNP near HLA-B, rs28367832G>A, reached genome-wide significance (OR 1.49, 95% CI 1.22-1.78, p = 7.27 × 10-9) in combined analyses; the association remained significant after excluding cases with clonal copy-neutral loss-of-heterozygosity affecting class I HLA genes (8.6% of cases and 0% of controls). SNPs in the HLA class II gene HLA-DPB1 and possibly class I (HLA-B) are associated with SAA. The replacement of Met76 to Val76 in certain HLA-DPB1 alleles might influence risk of SAA through mechanisms involving DP peptide binding specificity, expression, and/or other factors affecting DP function.


Assuntos
Anemia Aplástica/etiologia , Marcadores Genéticos , Predisposição Genética para Doença , Cadeias beta de HLA-DP/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Anemia Aplástica/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
8.
J Natl Cancer Inst ; 112(7): 770, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101285
9.
Cancer Epidemiol Biomarkers Prev ; 29(5): 1074-1078, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32108027

RESUMO

BACKGROUND: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis. METHODS: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated (P < 5 × 10-8) with high-density lipoprotein (HDL, n = 164), low-density lipoprotein (LDL, n = 137), total cholesterol (TC, n = 161), and triglycerides (TG, n = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance-weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI). RESULTS: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00-1.30) and MZL (OR = 1.09; 95% CI, 1.01-1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83-0.99), all at nominal significance (P < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99-1.19; P = 0.087). No associations were noteworthy after adjusting for multiple testing. CONCLUSIONS: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes. IMPACT: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.

10.
Hum Mol Genet ; 29(1): 70-79, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600786

RESUMO

We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10-13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10-12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.

11.
J Natl Cancer Inst ; 112(9): 929-937, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31845728

RESUMO

BACKGROUND: Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk. METHODS: Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up. RESULTS: Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2-4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5-<9 kg lost: HR = 0.75, 95% CI = 0.63 to 0.90; ≥9 kg lost: HR = 0.68, 95% CI = 0.50 to 0.93). Women who lost at least 9 kg and gained back some (but not all) of it were also at a lower risk of breast cancer. Other patterns of weight loss and gain over the two intervals had a similar risk of breast cancer to women with stable weight. CONCLUSIONS: These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.

12.
Cancer Epidemiol Biomarkers Prev ; 28(9): 1489-1494, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31196856

RESUMO

INTRODUCTION: There is limited research on associations of moderate-to-vigorous physical activity (MVPA) and sitting with risk of myeloid neoplasms (MN) or MN subtypes. We examined these associations in the Cancer Prevention Study-II Nutrition Cohort. METHODS: Among 109,030 cancer-free participants (mean age 69.2, SD 6.1 years) in 1999, 409 were identified as having been diagnosed with a MN [n = 155 acute myeloid leukemia (AML), n = 154 myelodysplastic syndromes (MDS), n = 100 other ML] through June 2013. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations of MVPA (MET-h/wk) and sitting (h/d) with risk of all MN, myeloid leukemia only, MDS, and AML. RESULTS: Compared with insufficient MVPA [>0-<7.5 metabolic equivalent hours/week (MET)-h/wk], the HR (95% CI) for meeting physical activity guidelines (7.5-<15 MET-h/wk MVPA) and risk of MN was 0.74 (95% CI, 0.56-0.98) and for doubling guidelines (15-<22.5 MET-h/wk) was 0.75 (0.53-1.07); however, there was no statistically significant association for higher MVPA (22.5+ MET-h/wk, HR, 0.93; 95% CI, 0.73-1.20). Similarly, meeting/doubling guidelines was associated with lower risk of MDS (HR, 0.57; 95% CI, 0.35-0.92/HR, 0.51; 95% CI, 0.27-0.98), but there was no association for 22.5+ MET-h/wk (HR, 0.93; 95% CI, 0.63-1.37). MVPA was not associated with risk of myeloid leukemia or AML. Sitting time was not associated with risk of any outcome. CONCLUSIONS: These results suggest that there may be a nonlinear association between MVPA and risk of MDS and possibly other MN. IMPACT: Further studies are needed to better understand the dose-response relationships between MVPA and risk of MDS, a highly fatal and understudied cancer.


Assuntos
Exercício Físico/fisiologia , Leucemia Mieloide Aguda/etiologia , Síndromes Mielodisplásicas/etiologia , Transtornos Mieloproliferativos/etiologia , Postura Sentada , Idoso , Feminino , Humanos , Masculino
13.
Br J Haematol ; 186(2): 243-254, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30977126

RESUMO

There is insufficient evidence linking excess body weight to risk of myeloid malignancies. We investigated this association using data from the Cancer Prevention Study-II (CPS-II), and a meta-analysis of published cohort studies. Among 152 090 CPS-II participants, 387 acute myeloid leukaemias (AML), 100 chronic myeloid leukaemias (CML) and 170 MDS were identified over 21 years of follow-up. In CPS-II, body mass index (BMI) was weakly associated with risk of CML (hazard ratio [HR] = 1·04, 95% confidence interval [CI]: 0·99-1·09 per 1 unit increase in BMI), AML (HR = 1·01, 95% CI: 0·98-1·03) and MDS (HR = 1·03, 95% CI: 0·99-1·07). After controlling for other anthropometric factors, no clear association was observed for height, BMI at age 18 years or weight change. In the meta-analysis (n = 7117 myeloid leukaemias), BMI 25-29·9 kg/m2 (HRpooled  = 1·36, 95% CI: 1·12-1·59) and BMI ≥30 kg/m2 (HRpooled  = 1·43, 95% CI: 1·18-1·69) were associated with higher risk of myeloid leukaemia overall, compared to a BMI <25 kg/m2 . Likewise, BMI ≥25 kg/m2 was positively associated with both AML and CML risk individually in the meta-analysis. These results underscore the need for large studies to detect associations with rare cancers, and show a modest, but positive association between excess body weight and myeloid malignancy risk.


Assuntos
Estatura , Índice de Massa Corporal , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/fisiopatologia , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
14.
Int J Cancer ; 145(10): 2647-2660, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30737780

RESUMO

Benzene is considered a carcinogen, mostly based on evidence of causality for myeloid leukemia from high levels of exposure in occupational studies. We used United States Environmental Protection Agency National Ambient Toxics Assessment (NATA) estimates of low-level ambient benzene to examine potential associations for the general public between benzene exposure and risk of hematologic cancers. Exposure was estimated by linking participants' residential address to the NATA benzene estimates for that census tract. Among 115,996 American Cancer Society Cancer Prevention Study-II Nutrition cohort participants (52,554 men, 63,442 women), 2,595 were diagnosed with incident hematologic cancer between 1997 and 2013. Extended Cox regression modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Among all participants, ambient benzene was positively associated with myelodysplastic syndromes (HR = 1.16, 95% CI: 1.01-1.33 per µg/m3 ) and T-cell lymphoma (HR = 1.29, 95% CI: 1.08-1.53 per µg/m3 ). Among men, ambient benzene was also positively associated with any hematologic malignancy (HR = 1.07, 95% CI: 1.01-1.15 per µg/m3 ) and follicular lymphoma (HR = 1.28, 95% CI: 1.09-1.50 per µg/m3 ). No significant associations were observed for women only, but associations were suggestive for MDS and T-cell lymphoma. It is possible that the NATA ambient benzene estimates are a better proxy for benzene exposure for men than women in this cohort. The results of this study support an association between ambient benzene and risk of hematologic malignancies, particularly MDS, T-cell lymphoma and follicular lymphoma. More research in large scale or pooled studies is needed to further explore these associations.


Assuntos
Poluentes Atmosféricos/toxicidade , Benzeno/toxicidade , Neoplasias Hematológicas/epidemiologia , Características de Residência/estatística & dados numéricos , Idoso , Monitorização de Parâmetros Ecológicos/estatística & dados numéricos , Feminino , Seguimentos , Neoplasias Hematológicas/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores Sexuais , Inquéritos e Questionários/estatística & dados numéricos , Estados Unidos/epidemiologia
15.
Front Oncol ; 9: 1539, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32064237

RESUMO

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.

16.
Am J Epidemiol ; 188(1): 102-109, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30325407

RESUMO

Social isolation is associated with higher mortality in studies comprising mostly white adults, yet associations among black adults are unclear. In this prospective cohort study, we evaluated whether associations of social isolation with all-cause, cardiovascular disease, and cancer mortality differed by race and sex. Adults enrolled in Cancer Prevention Study II in 1982/1983 were followed for mortality through 2012 (n = 580,182). Sex- and race-specific multivariable-adjusted hazard ratios and 95% confidence intervals were estimated for associations of a 5-point social isolation score with risk of death. Social isolation was associated with all-cause mortality in all subgroups (P for trend ≤ 0.005); for the most isolated versus the least isolated, the hazard ratios were 2.34 (95% confidence interval (CI): 1.58, 3.46) and 1.60 (95% CI: 1.41, 1.82) among black men and white men, respectively (P for interaction = 0.40) and 2.13 (95% CI: 1.44, 3.15) and 1.84 (95% CI: 1.68, 2.01) among black women and white women, respectively (P for interaction = 0.89). The association did not differ between black men and black women (P for interaction = 0.33) but was slightly stronger in white women than in white men (P for interaction = 0.01). Social isolation was associated with cardiovascular disease mortality in each subgroup (P for trend < 0.03) but with cancer mortality only among whites (P for trend < 0.0001). Subgroup differences in the influence of specific social isolation components were identified. Identifying and intervening with socially isolated adults could improve health outcomes.


Assuntos
Afro-Americanos/estatística & dados numéricos , Doenças Cardiovasculares/mortalidade , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Neoplasias/mortalidade , Isolamento Social , Adulto , Idoso , Doenças Cardiovasculares/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etnologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores Raciais , Fatores de Risco , Fatores Sexuais , Participação Social , Fatores Socioeconômicos , Estados Unidos/epidemiologia
17.
Int J Cancer ; 144(5): 1010-1016, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30117163

RESUMO

Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case-control studies nested within the Cancer Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition - Italy (EPIC-Italy) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes from 1,435 cases and 1,433 controls using inductively coupled plasma-mass spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models with each study result weighted by the within- and between-study variances. I2 values were calculated to estimate proportion of between study variation. Using common cut-points, cadmium levels were not associated with breast cancer risk in the CPS-II cohort (continuous RR = 1.01, 95% CI 0.76-1.34), but were inversely associated with risk in the EPIC- Italy (continuous RR = 0.80, 95% CI 0.61-1.03) and NSHDS cohorts (continuous RR = 0.73, 95% CI 0.54-0.97). The inverse association was also evident in the meta-analysis (continuous RR = 0.84, 95% CI 0.69-1.01) with low between-study heterogeneity. Large differences in lead level distributions precluded a meta-analysis of their association with breast cancer risk; no associations were found in the three studies. Adult cadmium and lead levels were not associated with higher risk of breast cancer in our large meta-analysis.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/etiologia , Cádmio/sangue , Chumbo/sangue , Idoso , Idoso de 80 Anos ou mais , Carcinógenos/toxicidade , Estudos de Casos e Controles , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Suécia
18.
Nat Commun ; 9(1): 4182, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305637

RESUMO

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.


Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 6/genética , Predisposição Genética para Doença , Macroglobulinemia de Waldenstrom/genética , Sequência de Bases , Proliferação de Células , Família , Genes Reporter , Técnicas de Genotipagem , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Padrões de Herança/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Fatores de Risco
19.
CA Cancer J Clin ; 68(6): 446-470, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30303518

RESUMO

In the United States, it is estimated that more than 1.7 million people will be diagnosed with cancer, and more than 600,000 will die of the disease in 2018. The financial costs associated with cancer risk factors and cancer care are enormous. To substantially reduce both the number of individuals diagnosed with and dying from cancer and the costs associated with cancer each year in the United States, government and industry and the public health, medical, and scientific communities must work together to develop, invest in, and implement comprehensive cancer control goals and strategies at the national level and expand ongoing initiatives at the state and local levels. This report is the second in a series of articles in this journal that, together, describe trends in cancer rates and the scientific evidence on cancer prevention, early detection, treatment, and survivorship to inform the identification of priorities for a comprehensive cancer control plan. Herein, we focus on existing evidence about established, modifiable risk factors for cancer, including prevalence estimates and the cancer burden due to each risk factor in the United States, and established primary prevention recommendations and interventions to reduce exposure to each risk factor.


Assuntos
Efeitos Psicossociais da Doença , Detecção Precoce de Câncer/métodos , Promoção da Saúde/métodos , Neoplasias/prevenção & controle , Prevenção Primária/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Assistência à Saúde , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/tendências , Feminino , Promoção da Saúde/economia , Promoção da Saúde/tendências , Estilo de Vida Saudável , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/epidemiologia , Neoplasias/etiologia , Prevalência , Prevenção Primária/economia , Prevenção Primária/tendências , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto Jovem
20.
Cancer Epidemiol Biomarkers Prev ; 27(10): 1186-1194, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30038049

RESUMO

Background: Antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG) proteins, especially pilus protein Gallo2178, have been consistently associated with colorectal cancer risk. Previous case-control studies and prospective studies with up to 8 years of follow-up, however, were unable to decipher the temporality of antibody responses to SGG in the context of the long-term multistep development of colorectal cancer. In this study, we analyzed a large U.S. colorectal cancer cohort consortium with follow-up beyond 10 years for antibody responses to SGG.Methods: We applied multiplex serology to measure antibody responses to 9 SGG proteins in participants of 10 prospective U.S. cohorts (CLUE, CPSII, HPFS, MEC, NHS, NYUWHS, PHS, PLCO, SCCS, and WHI) including 4,063 incident colorectal cancer cases and 4,063 matched controls. Conditional logistic regression was used to assess whether antibody responses to SGG were associated with colorectal cancer risk, overall and by time between blood draw and diagnosis.Results: Colorectal cancer risk was increased among those with antibody responses to Gallo2178, albeit not statistically significant [OR, 1.23; 95% confidence interval (CI), 0.99-1.52]. This association was stronger for cases diagnosed <10 years after blood draw (OR, 1.40; 95% CI, 1.09-1.79), but was not found among cases diagnosed ≥10 years after blood draw (OR, 0.79; 95% CI, 0.50-1.24).Conclusions: In a large cohort consortium, we reproduced the association of antibody responses to SGG Gallo2178 with colorectal cancer risk for individuals diagnosed within 10 years after blood draw.Impact: This timing-specific finding suggests that antibody responses to SGG are associated with increased colorectal cancer risk only after tumorigenesis has begun. Cancer Epidemiol Biomarkers Prev; 27(10); 1186-94. ©2018 AACR.


Assuntos
Anticorpos Antibacterianos/sangue , Formação de Anticorpos/imunologia , Proteínas de Bactérias/imunologia , Neoplasias Colorretais/imunologia , Infecções Estreptocócicas/complicações , Streptococcus gallolyticus subspecies gallolyticus/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/imunologia , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Infecções Estreptocócicas/microbiologia , Adulto Jovem
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