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Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (Ptrend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.
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Adenocarcinoma de Células Claras/etiologia , Adenocarcinoma Mucinoso/etiologia , Biomarcadores/sangue , Cistadenocarcinoma Seroso/etiologia , Neoplasias do Endométrio/etiologia , Neoplasias Ovarianas/etiologia , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/epidemiologia , Adulto , Hormônio Antimülleriano/sangue , Estudos de Casos e Controles , Estudos de Coortes , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/epidemiologia , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/epidemiologia , Pré-Menopausa , Prognóstico , Adulto JovemRESUMO
Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing Genome-wide association study (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2028 cases and 2109 controls to examine gene-smoking interactions at pathway/gene/single nucleotide polymorphism (SNP) level. Using the likelihood ratio test nested in logistic regression models and ingenuity pathway analysis (IPA), we examined 172 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, 3 manually curated gene sets, 3 nicotine dependency gene ontology pathways, 17 912 genes and 468 114 SNPs. None of the individual pathway/gene/SNP showed significant interaction with smoking after adjusting for multiple comparisons. Six KEGG pathways showed nominal interactions (P < 0.05) with smoking, and the top two are the pancreatic secretion and salivary secretion pathways (major contributing genes: RAB8A, PLCB and CTRB1). Nine genes, i.e. ZBED2, EXO1, PSG2, SLC36A1, CLSTN1, MTHFSD, FAT2, IL10RB and ATXN2 had P interaction < 0.0005. Five intergenic region SNPs and two SNPs of the EVC and KCNIP4 genes had P interaction < 0.00003. In IPA analysis of genes with nominal interactions with smoking, axonal guidance signaling $$\left(P=2.12\times 1{0}^{-7}\right)$$ and α-adrenergic signaling $$\left(P=2.52\times 1{0}^{-5}\right)$$ genes were significantly overrepresented canonical pathways. Genes contributing to the axon guidance signaling pathway included the SLIT/ROBO signaling genes that were frequently altered in pancreatic cancer. These observations need to be confirmed in additional data set. Once confirmed, it will open a new avenue to unveiling the etiology of smoking-associated pancreatic cancer.
Assuntos
Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Neoplasias Pancreáticas/etiologia , Transdução de Sinais , Fumar , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
BACKGROUND: Magnetic resonance imaging (MRI) yields important information on the development and current status of many different diseases. Whole-body MRI was accordingly made a part of the multicenter, population-based NAKO Health Study. The present analysis concerns the feasibility of the baseline MRI examination and various aspects of quality assurance over the period 2014-2019. METHODS: 32 252 participants in the NAKO Health Study, aged 20 to 74, who had no contraindication to MRI were invited to undergo scanning in one of five MRI study centers across Germany. The whole-body MRI scan took about one hour and consisted of sequences for the visualization of structural and functional features of the brain, musculoskeletal system, cardiovascular system, and thoracoabdominal system. A comprehensive quality-assurance assessment was carried out, with evaluation of adverse events, the completeness of the MRI protocols, the participants' subjective perceptions, and image quality. RESULTS: 31 578 participants (97.9%) were successfully included in the MRI study. They reported a high level of comfort and suffered no severe adverse events; mild adverse events occurred in only four participants. Depending on the imaging sequence, the image quality was rated as excellent in 80.2% to 96.8% of cases. Quality assessment with respect to structural features of the brain revealed high consistency across study centers, as well as with regard to age-and sex-based differences in brain volume (men, 1203.81 ± 102.06 cm³; women, 1068.10 ± 86.69 cm³). CONCLUSION: Whole-body MRI was successfully implemented in the NAKO baseline examination and was associated with high patient comfort and very good image quality. The imaging biomarkers of the brain confirmed previously observed differences based on age and sex, underscoring the feasibility of data pooling.
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OBJECTIVE: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. METHODS: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. RESULTS: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. INTERPRETATION: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure.
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Esclerose Lateral Amiotrófica/etiologia , Esclerose Lateral Amiotrófica/mortalidade , Fumar/efeitos adversos , Adulto , Fatores Etários , Idoso , Esclerose Lateral Amiotrófica/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Risco , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3'-untranslated region, which may influence VDR mRNA stability. METHODS: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. RESULTS: The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). CONCLUSIONS: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status.
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Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Adulto , Idoso , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Pessoa de Meia-Idade , Estudos Prospectivos , RiscoRESUMO
A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.
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Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Linfoma não Hodgkin/genética , Estudos de Casos e Controles , Feminino , Heterogeneidade Genética , Estudo de Associação Genômica Ampla/métodos , Heterozigoto , Humanos , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: To identify reproductive, lifestyle, hormonal, and other correlates of circulating antimüllerian hormone (AMH) concentrations in mostly late premenopausal women. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): A total of 671 premenopausal women not known to have cancer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Concentrations of AMH were measured in a single laboratory using the picoAMH ELISA. Multivariable-adjusted median (and interquartile range) AMH concentrations were calculated using quantile regression for several potential correlates. RESULT(S): Older women had significantly lower AMH concentrations (≥40 [n = 444] vs. <35 years [n = 64], multivariable-adjusted median 0.73 ng/mL vs. 2.52 ng/mL). Concentrations of AMH were also significantly lower among women with earlier age at menarche (<12 [n = 96] vs. ≥14 years [n = 200]: 0.90 ng/mL vs. 1.12 ng/mL) and among current users of oral contraceptives (n = 27) compared with never or former users (n = 468) (0.36 ng/mL vs. 1.15 ng/mL). Race, body mass index, education, height, smoking status, parity, and menstrual cycle phase were not significantly associated with AMH concentrations. There were no significant associations between AMH concentrations and androgen or sex hormone-binding globulin concentrations or with factors related to blood collection (e.g., sample type, time, season, and year of blood collection). CONCLUSION(S): Among premenopausal women, lower AMH concentrations are associated with older age, a younger age at menarche, and currently using oral contraceptives, suggesting these factors are related to a lower number or decreased secretory activity of ovarian follicles.
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Hormônio Antimülleriano/sangue , Estilo de Vida , Reserva Ovariana , Pré-Menopausa/sangue , Adulto , Fatores Etários , Ásia , Biomarcadores/sangue , Anticoncepcionais Orais Hormonais/uso terapêutico , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Globulina de Ligação a Hormônio Sexual/análise , Congêneres da Testosterona/sangue , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. METHODS: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. RESULTS: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. CONCLUSIONS: These data suggest several plausible genetic links between DLBCL and SLE.
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OBJECTIVE: The association between consumption of fruit and vegetables and risk of ovarian cancer is still unclear from a prospective point of view. METHODS: Female participants (n = 325,640) of the European Prospective Investigation into Cancer and Nutrition study, free of any cancer at baseline, were followed on average for 6.3 years to develop ovarian cancer. During 2,049,346 person-years, 581 verified cases of primary, invasive epithelial ovarian cancer were accrued. Consumption of fruits and vegetables as well as subgroups of vegetables, estimated from validated dietary questionnaires and calibrated thereafter, was related to ovarian cancer incidence in multivariable hazard regression models. Histologic subtype specific analyses were done. RESULTS: Total intake of fruit and vegetables, separately or combined, as well as subgroups of vegetables (fruiting, root, leafy vegetables, cabbages) was unrelated to risk of ovarian cancer. A high intake of garlic/onion vegetables was associated with a borderline significant reduced risk of this cancer. The examination by histologic subtype indicated some differential effects of fruit and vegetable intake on ovarian cancer risk. CONCLUSION: Overall, a high intake of fruits and vegetables did not seem to protect from ovarian cancer. Garlic/onion vegetables may exert a beneficial effect. The study of the histologic subtype of the tumor warrants further investigation.
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Dieta , Frutas , Neoplasias Ovarianas/prevenção & controle , Verduras , Adulto , Idoso , Estudos Epidemiológicos , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Estilo de Vida , Pessoa de Meia-Idade , Inquéritos Nutricionais , Neoplasias Ovarianas/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
High circulating concentration of insulin-like growth factor-I (IGF-I) and low circulating concentration of IGF binding protein-3 (IGFBP-3) have been associated with increased risk for breast, prostate, and colorectal cancers. Building on previous work in the Multiethnic Cohort (MEC) showing significant differences in IGF-I levels across racial/ethnic groups, we investigated which lifestyle and dietary factors are associated with levels of IGF-I and IGFBP-3 in a random sample of 1,000 MEC participants, which included Native Hawaiian, African American, Japanese, Latino, and White men and women. Crude analyses confirmed the existence of differences in protein levels with race/ethnicity, sex, age, and body size. Reproductive, physical activity, smoking, and diet variables had less consistent effects. In multivariate analyses, IGF-I levels were lower and IGFBP-3 were higher in females versus males. IGF-I and IGFBP-3 declined with increasing age in both genders. Women in the highest quartile of body mass index showed depressed IGF-I and IGFBP-3 levels; in men, height was significantly positively associated with both proteins. In women, alcohol was directly associated with IGFBP-3. Both proteins were lowest among female Latinos. IGF-I was highest among female African Americans. In men, IGFBP-3 was lowest among African Americans. Overall, although these factors were statistically significant determinants of IGF-related protein levels, they did not explain much of the variation in these levels. A positive correlation was found between IGF-I levels (ng/mL) and colon cancer incidence rates (per 100,000) within the MEC by race/ethnicity for both sexes but not for either breast or prostate cancer.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias Colorretais/epidemiologia , Etnicidade , Comportamento Alimentar , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Estilo de Vida , Neoplasias da Próstata/epidemiologia , Fatores Etários , Idoso , Neoplasias da Mama/sangue , Estudos de Coortes , Neoplasias Colorretais/sangue , Comparação Transcultural , Estudos Transversais , Feminino , Havaí , Humanos , Los Angeles , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Valores de Referência , Fatores de Risco , Fatores Sexuais , Estatística como AssuntoRESUMO
BACKGROUND: A moderate association exists between body mass index (BMI) and colorectal cancer. Less is known about the effect of weight change. OBJECTIVE: We investigated the relation between BMI and weight change and subsequent colon and rectal cancer risk. DESIGN: This was studied among 328,781 participants in the prospective European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating study (mean age: 50 y). Body weight was assessed at recruitment and on average 5 y later. Self-reported weight change (kg/y) was categorized in sex-specific quintiles, with quintiles 2 and 3 combined as the reference category (men: -0.6 to 0.3 kg/y; women: -0.4 to 0.4 kg/y). In the subsequent years, participants were followed for the occurrence of colon and rectal cancer (median period: 6.8 y). Multivariable Cox proportional hazards regression analyses were used to study the association. RESULTS: A total of 1261 incident colon cancer and 747 rectal cancer cases were identified. BMI at recruitment was statistically significantly associated with colon cancer risk in men (HR: 1.04; 95% CI: 1.02, 1.07). Moderate weight gain (quintile 4) in men increased risk further (HR: 1.32; 95% CI: 1.04, 1.68), but this relation did not show a clear trend. In women, BMI or weight gain was not related to subsequent risk of colon cancer. No statistically significant associations for weight loss and colon cancer or for BMI and weight changes and rectal cancer were found. CONCLUSIONS: BMI attained at adulthood was associated with colon cancer risk. Subsequent weight gain or loss was not related to colon or rectal cancer risk in men or women.
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Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Aumento de Peso , Redução de Peso , Adulto , Índice de Massa Corporal , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Incidência , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Atividade Motora , Estado Nutricional , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND: There is limited evidence for an association between the pattern of lifetime alcohol use and cause-specific risk of death. METHODS: Multivariable hazard ratios were estimated for different causes of death according to patterns of lifetime alcohol consumption using a competing risks approach: 111 953 men and 268 442 women from eight countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study were included. Self-reported alcohol consumption at ages 20, 30, 40 or 50 years and at enrollment were used for the analysis; 26 411 deaths were observed during an average of 12.6 years of follow-up. RESULTS: The association between lifetime alcohol use and death from cardiovascular diseases was different from the association seen for alcohol-related cancers, digestive, respiratory, external and other causes. Heavy users (>5 drinks/day for men and >2.5 drinks/day for women), regardless of time of cessation, had a 2- to 5-times higher risk of dying due to alcohol-related cancers, compared with subjects with lifetime light use (≤1 and ≤0.5 drink/week for men and women, respectively). Compared with lifetime light users, men who used <5 drinks/day throughout their lifetime had a 24% lower cardiovascular disease mortality (95% confidence interval 2-41). The risk of death from coronary heart disease was also found to be 34-46% lower among women who were moderate to occasionally heavy alcohol users compared with light users. However, this relationship was only evident among men and women who had no chronic disease at enrollment. CONCLUSIONS: Limiting alcohol use throughout life is associated with a lower risk of death, largely due to cardiovascular disease but also other causes. However, the potential health benefits of alcohol use are difficult to establish due to the possibility of selection bias and competing risks related to diseases occurring later in life.
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Consumo de Bebidas Alcoólicas/epidemiologia , Doenças Cardiovasculares/mortalidade , Neoplasias/mortalidade , Adulto , Idoso , Causas de Morte , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. METHODS: Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. RESULTS: Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, P(trend) = 2 x 10(-26)), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, P(trend) = 1 x 10(-10)) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, P(trend) = 5 x 10(-8)) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, P(trend) = 2 x 10(-5); rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, P(trend) = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. CONCLUSIONS: In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.
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Povo Asiático/genética , Cromossomos Humanos Par 15 , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 6 , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Fumar/efeitos adversos , Tabagismo/etnologia , Tabagismo/genética , População Branca/genética , Adenocarcinoma/etnologia , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá/epidemiologia , Carcinoma de Células Grandes/etnologia , Carcinoma de Células Grandes/genética , Carcinoma de Células Pequenas/etnologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Europa (Continente) , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Homozigoto , Humanos , Cooperação Internacional , Japão/epidemiologia , Coreia (Geográfico)/epidemiologia , Desequilíbrio de Ligação/genética , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Controle de Qualidade , Medição de Risco , Fatores de Risco , Singapura/epidemiologia , Fumar/genética , Estados Unidos/epidemiologiaRESUMO
Insulin-like growth factor (IGF-I) and prolactin have been found to be associated with breast cancer risk and with mammographic density. In a pooled analysis from 4 geographic locations, we investigated the association of percent mammographic density with serum levels of IGF-I, IGFBP-3 and prolactin. The pooled data set included 1,327 pre- and postmenopausal women: Caucasians from Norway, Arizona and Hawaii, Japanese from Hawaii and Japan, Latina from Arizona, and Native Hawaiians from Hawaii. Serum samples were assayed for IGF-I, IGFBP-3 and prolactin levels using ELISA assays. Mammographic density was quantified using a computer-assisted density method. After stratification by menopausal status, multiple regression models estimated the relation between serum analytes and breast density. All serum analytes except prolactin among postmenopausal women differed significantly by location/ethnicity group. Among premenopausal subjects, IGF-I levels and the molar ratio were highest in Hawaii, intermediate in Japan and lowest in Arizona. For IGFBP-3, the order was reversed. Among postmenopausal subjects, Norwegian women had the highest IGF-I levels and women in Arizona had the lowest while women in Japan and Hawaii had intermediate levels. We observed no significant relation between percent density and IGF-I or prolactin levels among pre-and postmenopausal women. The significant differences in IGF-I levels by location but not ethnicity suggest that environmental factors influence IGF-I levels, whereas percent breast density varies more according to ethnic background than by location. Based on this analysis, the influence of circulating levels of IGF-I, IGFBP-3, and prolactin on percent density appears to be very small.
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Mama/patologia , Etnicidade , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Mamografia , Prolactina/sangue , Arizona/etnologia , Povo Asiático , Índice de Massa Corporal , Ensaio de Imunoadsorção Enzimática , Feminino , Havaí/etnologia , Hispânico ou Latino , Humanos , Japão/etnologia , Pessoa de Meia-Idade , Noruega/etnologia , Pós-Menopausa , Pré-Menopausa , População BrancaRESUMO
Insulin-like growth factor-I (IGF-I) has been proposed as the link between diet and breast cancer risk. Due to their estrogen-like structure, soy isoflavones may affect IGF-I levels in a similar way as exogenous estrogens. In a cross-sectional design, we compared IGF-I levels between women with high and low soy intake. The analysis included 611 pre- and postmenopausal women: Japanese in Japan and Japanese and Caucasians in Hawaii. The subjects had participated in a previous study, were never diagnosed with breast cancer, provided a screening mammogram and a blood sample, and completed validated food-frequency questionnaires. The same laboratory analyzed all serum samples for IGF-I and IGF binding protein (IGFBP)-3 by enzyme-linked immunosorbent assay. We estimated covariate-adjusted mean IGF-I and IGFBP-3 levels by tofu intake. The respective mean IGF-I levels were 213, 257, and 255 ng/ml for Japanese in Japan, Japanese in Hawaii, and Caucasians in Hawaii. Tofu intake was higher in Japan than among Japanese and Caucasians in Hawaii (11.0 vs. 9.4 and 4.9 g/1,000 kcal). Mean IGF-I levels were 11% lower among women in the highest tofu intake category compared with the lowest, but the difference in IGF-I levels between the highest and lowest tofu category was only significant among women in Japan. Inclusion of total energy, total protein, meat, and dairy intake did not materially alter the association between tofu consumption and IGF-I levels. These findings suggest that a diet rich in soy foods and low in meats may be related to lower IGF-I levels, but it is unclear whether soy or other characteristics of diet and lifestyle are responsible for this association.
Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Alimentos de Soja , Neoplasias da Mama/diagnóstico por imagem , Estudos Transversais , Inquéritos sobre Dietas , Ensaio de Imunoadsorção Enzimática , Feminino , Havaí/epidemiologia , Humanos , Isoflavonas/administração & dosagem , Japão/epidemiologia , Japão/etnologia , Mamografia , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Alterations in the insulin-like growth factor-I (IGF-I) system have been proposed as a metabolic link between nutritional factors and cancer risk. AIM OF THE STUDY: This study explored dietary determinants of circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels among premenopausal women from different ethnic groups. METHODS: In a cross-sectional design, 258 women with a mean age of 43 +/- 2.7 years donated blood approximately 5 days after ovulation and completed a validated Food Frequency Questionnaire. The majority of the 97 Caucasian, 96 Asian, and 65 Mixed/Other subjects were born in the US. Serum concentrations of IGF-I and IGFBP-3 were measured by double-antibody ELISA. After creating quartiles for 13 food and 13 nutrient density variables, least-square means of IGF-I, IGFBP-3, and the IGF-I/IGFBP-3 ratio were calculated by quartile, while adjusting for age, ethnicity, body mass index, and year of laboratory analysis. RESULTS: Whereas body mass index and dietary intakes varied significantly by ethnicity, IGF-I, IGFBP-3, and their ratio were similar by group. As the only food, fish showed a suggestive inverse association with IGF-I and the IGF-I/ IGFBP-3 ratio. Dietary fiber and vitamin A were positively related to IGF-I (p = 0.004 and 0.03), zinc with IGFB-3 (p = 0.0008), and iron with the IGF-I/IGFBP-3 ratio (p = 0.048), but the differences between the bottom and top quartile were less than 10%. Total energy, protein, carbohydrates, and total fat intake were not related to any serum measurements. CONCLUSIONS: This study detected no ethnic differences in serum IGF-I, but it showed weak associations with dietary variables that require further investigation.
Assuntos
Etnicidade/estatística & dados numéricos , Comportamento Alimentar , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Pré-Menopausa/sangue , Adulto , Ásia/etnologia , Índice de Massa Corporal , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/métodos , Comportamento Alimentar/etnologia , Feminino , Havaí , Humanos , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Pré-Menopausa/etnologia , Fatores de Risco , Inquéritos e Questionários , População Branca/estatística & dados numéricosRESUMO
Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.
Assuntos
Dieta , Glycine max , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Pré-Menopausa/sangue , Adulto , Distribuição de Qui-Quadrado , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Isoflavonas/urina , Pessoa de Meia-Idade , Alimentos de Soja , Proteínas de Soja/administração & dosagemRESUMO
Our study investigated the association of breast cancer risk as assessed by mammographic density with insulin-like growth factor I (IGF-I) and one of its binding proteins (IGFBP-3) in healthy premenopausal women with different ethnic backgrounds. In a cross-sectional design, we analyzed the baseline mammograms and fasting serum samples (collected 5 days after ovulation) of premenopausal women entering a nutritional intervention. Serum concentrations of IGF-I and IGFBP-3 were measured by double-antibody ELISA. Mammographic densities were assessed using a computer-assisted method. We calculated Spearman correlation coefficients between mammographic characteristics and analytes and estimated means of mammographic characteristics by quartiles of IGF-I and IGFBP-3 while adjusting for age, body mass index (BMI) and reproductive factors. In this group of 240 women, IGF-I, IGFBP-3 and percent densities did not differ significantly by ethnicity. Whereas mammographic densities were not associated with IGF-I, we found an inverse relation with IGFBP-3 (r(s) = -0.15, p = 0.02) and a positive association with the IGF-I/IGFBP-3 ratio (r(s) = 0.13, p = 0.04). The size of the dense areas was not associated with the analytes, but the size of the nondense areas was correlated directly with IGFBP-3 (r(s) = 0.20, p = 0.002) and inversely with the molar ratio (r(s) = -0.19, p = 0.004). These associations were limited to women with a BMI of less than 25 kg/m(2). These results suggest that the balance of circulating IGF-I and IGFBP-3 levels may influence the growth of the fatty part of the breast more than the epithelial and stromal breast tissue, but the exact mechanism of action needs to be explored in more detail.