Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 258
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Int J Epidemiol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566221

RESUMO

BACKGROUND: Obesity is an established risk factor for several cancers. Adult weight gain has been associated with increased cancer risk, but studies on timing and duration of adult weight gain are relatively scarce. We examined the impact of BMI (body mass index) and weight changes over time, as well as the timing and duration of excess weight, on obesity- and non-obesity-related cancers. METHODS: We pooled health data from six European cohorts and included 221 274 individuals with two or more height and weight measurements during 1972-2014. Several BMI and weight measures were constructed. Cancer cases were identified through linkage with national cancer registries. Hazard ratios (HRs) of cancer with 95% confidence intervals (CIs) were derived from time-dependent Cox-regression models. RESULTS: During follow-up, 27 881 cancer cases were diagnosed; 9761 were obesity-related. The HR of all obesity-related cancers increased with increasing BMI at first and last measurement, maximum BMI and longer duration of overweight (men only) and obesity. Participants who were overweight before age 40 years had an HR of obesity-related cancers of 1.16 (95% CI 1.02, 1.32) and 1.15 (95% CI 1.04, 1.27) in men and women, respectively, compared with those who were not overweight. The risk increase was particularly high for endometrial (70%), male renal-cell (58%) and male colon cancer (29%). No positive associations were seen for cancers not regarded as obesity-related. CONCLUSIONS: Adult weight gain was associated with increased risk of several major cancers. The degree, timing and duration of overweight and obesity also seemed to be important. Preventing weight gain may reduce the cancer risk.

2.
Clin Breast Cancer ; 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31303563

RESUMO

INTRODUCTION: Oncoplastic breast surgery (OBS) has been implemented with increasing frequency in the treatment of breast cancer. The aim of this study was to compare the oncologic outcome after OBS to the outcome after conventional breast-conserving surgery (BCS) in patients with invasive breast cancer. PATIENTS AND METHODS: In all, 197 patients treated with OBS were compared to 1399 patients treated with conventional BCS from 2008 to 2013. We evaluated nonradical primary tumor excision, time to initiation of adjuvant therapy, disease-free survival (risk of recurrent disease), and survival (cause specific and overall). Identification of patients and follow-up were made using the Danish Breast Cancer Cooperative Group registry and the Danish Cause of Death registry. Multivariate logistic regression and the Cox proportional hazard analysis were used to obtain odds ratios and hazard ratios with 95% confidence intervals (CI). RESULTS: There was a lower risk for nonradical primary tumor excision for patients undergoing OBS versus conventional BCS (adjusted odds ratio:95% CI, 0.50:0.29-0.84). No significant differences were found with regard to a delay in initiation of adjuvant chemotherapy (adjusted hazard ratio:95% CI, 1.14:0.89-1.45) or radiotherapy (0.91:0.71-1.16), disease-free survival (1.23:0.61-2.47), breast cancer as cause of death (1.46:0.52-4.09), breast cancer as underlying or multiple cause of death (0.90:0.34-2.37), or overall survival (0.90:0.51-1.60). CONCLUSION: We found no significant differences in oncologic outcome comparing OBS to conventional BCS. However, a lower risk of nonradical primary tumor excision was found for patients treated with OBS. These results indicate that OBS is a safe procedure.

3.
Breast Cancer Res ; 21(1): 84, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358030

RESUMO

BACKGROUND: Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts its functions through the vitamin D receptor (VDR), and the aim of the current study was to investigate if the expression of VDR in invasive breast tumors is associated with breast cancer prognosis. METHODS: VDR expression was evaluated in a tissue microarray of 718 invasive breast tumors. Covariation between VDR expression and established prognostic factors for breast cancer was analyzed, as well as associations between VDR expression and breast cancer mortality. RESULTS: We found that positive VDR expression in the nuclei and cytoplasm of breast cancer cells was associated with favorable tumor characteristics such as smaller size, lower grade, estrogen receptor positivity and progesterone receptor positivity, and lower expression of Ki67. In addition, both intranuclear and cytoplasmic VDR expression were associated with a low risk of breast cancer mortality, hazard ratios 0.56 (95% CI 0.34-0.91) and 0.59 (0.30-1.16) respectively. CONCLUSIONS: This study found that high expression of VDR in invasive breast tumors is associated with favorable prognostic factors and a low risk of breast cancer death. Hence, a high VDR expression is a positive prognostic factor.

4.
Int J Cancer ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

5.
BMC Cancer ; 19(1): 626, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238899

RESUMO

BACKGROUND: Sentinel node biopsy (SNB) is the standard procedure for axillary staging in patients with clinically lymph node negative invasive breast cancer. Completion axillary lymph node dissection (c-ALND) may not be necessary for all patients as a significant number of patients have no further metastases in non-sentinel nodes (non-SN) and c-ALND may not improve survival. The first aim of our study is to identify clinicopathological determinants associated with non-SN metastases. The second aim is to determine the impact of the number of sentinel node (SN) with macro-metastases and the type of SN metastases on metastatic involvement in non-SN. METHODS: This is a retrospective study of 602 patients with primary invasive breast cancer operated on with SNB and c-ALND in Lund and Malmö during 2008-2013. All these patients had micro- and/or macro-metastases in SNs. Information was retrieved from the national Information Network for Cancer Care (INCA). The risk of metastases to non-SNs were analyzed in relation to clinicopathological determinants such as age, screening mammography, tumour size, tumour type, histological grade, estrogen status, progesterone status, HER2 status, multifocality and lymphovascular invasion. Additionally, we compared the association between the number of the SN and the type of metastases in SN with the risk of metastases to non-SNs. Binary logistic regression was used, yielding odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We found that 211 patients (35%) had metastases in non-SNs and 391 patients (65%) had no metastases in non-SNs. Lobular type (18%) of breast cancer (1.73; 1.0 1-2.97) and multifocal (31.3%) tumours (2.20; 1.41-3.44) had a high risk of non-SNs metastases. As compared to only micro-metastases, the presence of macro-metastases in SNs was associated with a high risk of metastases to non-SNs (4.91; 3.01-8.05). The number of SN with macro-metastases, regardless of the number of SNs removed by surgery, increases the risk of finding non-SNs with metastases. The total number of SN removed by surgery had no impact on diagnosis of metastases in non-SNs. No statistically significant associations were observed regarding other studied determinants. CONCLUSION: We conclude in the present study that lobular cancer and multifocal tumours were associated with a high risk of non-SN involvement. The presence of the macro-metastases in SNs and the number of SN with macro-metastases has a positive association with presence of metastases in non-SNs. The total number of SNs removed by surgery had no impact on finding metastases in non-SNs. These factors may be valuable considering whether or not to omit c-ALND.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30958561

RESUMO

Objectives The aim of this study was to investigate if exposure to chemicals in the workplace was associated with an increased risk of postmenopausal breast cancer. Methods The study comprised women born 1923-1950 living in Malmö city, Sweden, 1991-1996, and enrolled for a prospective population cohort study. Occupational exposure to various chemicals was assessed from job-exposure matrices. An extensive set of individual data on hormonal breast cancer risk factors were collected via a baseline questionnaire and used for confounding control. First time diagnoses of invasive breast cancer were identified through the Swedish Cancer Registry until end of follow-up on 31 December 2013. Results Of 16 084 women, 1011 were diagnosed with breast cancer. Women exposed to chemicals in their occupational environment had a statistically significant increased risk [adjusted hazard ratio (HR adj) 1.26, 95% confidence interval (CI) 1.02-1.54] of breast cancer, and the risk correlated with duration of exposure. Investigation of risk in association with specific chemicals showed a non-significantly elevated risk after exposure to organic solvents. More than ten years of exposure to diesel exhaust was associated with an increased risk (HR adj1.69, 95% CI 1.01-2.82). Occupational chemical exposures account for 2% of the breast cancer cases in this population. Conclusions Occupational exposure to chemicals in general was associated with an elevated risk of breast cancer. A slight elevation of risk was seen after exposure to organic solvents. A statistically significant elevation of risk after >10 years of exposure to diesel exhaust was an unexpected finding.

7.
Int J Epidemiol ; 2019 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945727

RESUMO

BACKGROUND: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. METHODS: Altogether 510 471 individuals from six European cohorts, with a mean age of 43.1 years, were included. We used the triglyceride glucose product (TyG index) as a surrogate measure for insulin resistance. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with 10 common obesity-related cancers, and quantified the proportion of the effect of BMI mediated through TyG index on the log-transformed hazard ratio (HR) scale. RESULTS: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney HR per one standard deviation increase 1.13, 95% confidence interval: 1.07 to 1.20], liver (1.13, 1.04 to 1.23), pancreas (1.12, 1.06 to 1.19), colon (1.07, 1.03 to 1.10) and rectum (1.09, 1.04 to 1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%) and colon (20%); smaller proportions for kidney (15%) and liver (11%). Little or no mediation was observed for breast (postmenopausal), endometrial and ovarian cancer. Results were similar for males and females, except for pancreatic cancer where the proportions mediated were 20% and 91%, respectively. CONCLUSIONS: The TyG index was associated with increased risk of cancers of the digestive system and substantially mediated the effect of BMI, suggesting that insulin resistance plays a promoting role in the pathogenesis of gastrointestinal cancers.

8.
Int J Cancer ; 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30815851

RESUMO

Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age-course. We created two random 50-50% cohorts from six European cohorts comprising 813,927 individuals. In the "discovery cohort", we used Cox regression with attained age as time-scale and tested interactions between body mass index (BMI), blood pressure, plasma glucose, triglycerides and cholesterol, and attained age in relation to cancer risk. Results with a p-value below 0.05 were additionally tested in the "replication cohort" where a replicated result was considered evidence of a linear interaction with attained age. These findings were investigated by flexible parametric survival models for any age-plateaus in their shape of associations with cancer risk across age. Consistent with other studies, BMI was negatively related to breast cancer risk (n cases = 11,723) among younger (premenopausal) women. However, the association remained negative for several years after menopause and, although gradually weakening over age, the association became positive only at 62 years of age. This linear and positive age-interaction was also found for triglycerides and breast cancer, and for BMI and triglycerides in relation to liver cancer among men (n cases = 444). These findings are unlikely to be due to chance owing to the replication. The linear age-interactions in breast cancer may suggest an influence by other age-related factors than menopause; however, further investigation of age-related effect modifiers in both breast and liver cancer is needed.

9.
Cancer Epidemiol Biomarkers Prev ; 28(5): 935-942, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30700444

RESUMO

BACKGROUND: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. METHODS: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. RESULTS: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non-small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. CONCLUSIONS: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. IMPACT: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

10.
Carcinogenesis ; 40(3): 432-440, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30590402

RESUMO

DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case-control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10-1.24, P = 8.45 × 10-7) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89-0.95, P = 1.02 × 10-6) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What's more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 × 10-4). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer.

11.
Eur J Nutr ; 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30535794

RESUMO

PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases. CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

12.
Eur J Cancer Prev ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30422929

RESUMO

The World Cancer Research Fund International has concluded strong evidence for that high intake of dairy products and foods containing dietary fiber and low intake of processed meat are associated with decreased risk of colorectal cancer (CRC). As food items are consumed together, it is important to study dietary patterns. The aim of the present study was to examine the association between an a priori constructed dietary index and incident CRC and between intake of processed meat, fiber, and dairy products and CRC. In the Malmö Diet and Cancer study cohort, 923 cases of CRC were identified, during 502 136 person-years of follow-up. A Colorectal Diet Quality Index (CDQI) was constructed regarding intakes of processed meat, fiber, and dairy products in relation to CRC. Higher index indicated a higher dietary quality. Higher CDQI was associated with lower risk of CRC [hazard ratios (HR): 0.57 for highest compared with lowest quintile; 95% confidence interval (CI): 0.43, 0.75; P<0.001]. Intake of dairy products was inversely associated with risk of CRC [HR for highest vs. lowest quintile was 0.77 (CI: 0.62, 0.96); P=0.008], as was dietary fiber (HR for highest vs. lowest quintile was 0.77 (CI: 0.61, 0.98); P=0.043). High intake of processed meat was associated with CRC (HR for highest vs. lowest quintile was 1.31; CI: 1.05, 1.63; P=0.012). High adherence to a predefined CRC-specific diet quality index was inversely associated with the risk of CRC and gave a stronger association with CRC, than when analyzing the components of the CDQI individually.

13.
Cancer Res ; 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30425058

RESUMO

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between pre-diagnostic concentrations of 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)2D and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. Odds ratios (OR) for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest versus lowest study-specific fifth was 1.22, 95% CI 1.13-1.31; P trend<0.001). However, this association varied by disease aggressiveness (Pheterogeneity=0.014); higher circulating 25(OH)D was associated with a higher risk of non-aggressive disease (OR per 80 percentile increase=1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of non-aggressive prostate cancer may be influenced by detection bias.

14.
Plast Reconstr Surg Glob Open ; 6(8): e1912, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30324078

RESUMO

Background: Arm lymphedema is a well-recognized complication after breast cancer surgery that negatively impacts patients' quality of life, both physiologically and psychologically. Lymph stasis and inflammation result in excess formation of adipose tissue, which makes removal of the deposited subcutaneous fat necessary to eliminate the excess volume. Liposuction, combined with postoperative controlled compression therapy (CCT), is the only treatment that gives complete reduction of the excess volume. The aim of this study was to evaluate the 5-year results after liposuction in combination with CCT. Methods: Patients consecutively operated on between 1993 and 2012 were identified from the lymphedema registry, comprising all patients with nonpitting lymphedema treated with liposuction and CCT in our department. Standardized forms were used to collect pre-, peri-, and postoperative data. Results: One hundred five women with nonpitting edema were treated. The mean interval between the breast cancer operation and lymphedema start was 2.9 ± 5.0 years, the mean duration of lymphedema was 10 ± 7.4 years, and the preoperative mean excess volume was 1,573 ± 645 ml. The mean volume aspirated was 1,831 ± 599 ml. Postoperative mean reduction 5 years postoperatively was 117% ± 26% as compared with the healthy arm. Conclusion: Liposuction is an effective method for the treatment of chronic, nonpitting, arm lymphedema resistant to conservative treatment. The volume reduction remains complete after 5 years.

15.
Int J Cancer ; 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30259989

RESUMO

Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.

16.
Int J Epidemiol ; 47(6): 1760-1771, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29901778

RESUMO

Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls. We used conditional logistic regression to evaluate the association between circulating cotinine and lung cancer, and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration), using receiver-operating characteristic (ROC) curve analysis. Results: We observed a strong positive association between cotinine and lung cancer risk for current smokers [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32-1.47]. Cotinine concentrations consistent with active smoking (≥115 nmol/L) were common in former smokers (cases: 14.6%; controls: 9.2%) and rare in never smokers (cases: 2.7%; controls: 0.8%). Former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L) also showed increased lung cancer risk. For current smokers, the risk-discriminative performance of cotinine combined with self-reported smoking (AUCintegrated: 0.69, 95% CI: 0.68-0.71) yielded a small improvement over self-reported smoking alone (AUCsmoke: 0.66, 95% CI: 0.64-0.68) (P = 1.5x10-9). Conclusions: Circulating cotinine concentrations are consistently associated with lung cancer risk for current smokers and provide additional risk-discriminative information compared with self-report smoking alone.

17.
Int J Cancer ; 143(12): 3071-3082, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29756343

RESUMO

Previous studies on metabolic factors and bladder cancer (BC) risk have shown inconsistent results and have commonly not investigated associations separately by sex, smoking, and tumor invasiveness. Among 811,633 participants in six European cohorts, we investigated sex-specific associations between body mass index (BMI), mid-blood pressure (BP, [systolic + diastolic]/2), plasma glucose, triglycerides, total cholesterol and risk of BC overall, non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Among men, we additionally assessed additive interactions between metabolic factors and smoking on BC risk. During follow-up, 2,983 men and 754 women were diagnosed with BC. Among men, triglycerides and BP were positively associated with BC risk overall (hazard ratio [HR] per standard deviation [SD]: 1.17 [95% confidence interval (CI) 1.06-1.27] and 1.09 [1.02-1.17], respectively), and among women, BMI was inversely associated with risk (HR: 0.90 [0.82-0.99]). The associations for BMI and BP differed between men and women (pinteraction ≤ 0.005). Among men, BMI, cholesterol and triglycerides were positively associated with risk for NMIBC (HRs: 1.09 [95% CI 1.01-1.18], 1.14 [1.02-1.25], and 1.30 [1.12-1.48] respectively), and BP was positively associated with MIBC (HR: 1.23 [1.02-1.49]). Among women, glucose was positively associated with MIBC (HR: 1.99 [1.04-3.81]). Apart from cholesterol, HRs for metabolic factors did not significantly differ between MIBC and NMIBC, and there were no interactions between smoking and metabolic factors on BC. Our study supports an involvement of metabolic aberrations in BC risk. Whilst some associations were significant only in certain sub-groups, there were generally no significant differences in associations by smoking or tumor invasiveness.

18.
Eur Thyroid J ; 7(1): 27-33, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29594051

RESUMO

Objective: The aim was to compare the vitamin D levels in patients with Graves disease (GD) with the general population and to correlate the vitamin D levels with laboratory and clinical parameters in GD. Moreover, we examined the genetic variation in genes involved in the vitamin D metabolism and their association with GD. Methods: The levels of vitamin D were compared in 292 patients with newly diagnosed GD and 2,305 controls. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR), vitamin D binding protein (DBP), and 1-α-hydroxylase (CYP27B1) were examined for association with GD and/or Graves ophthalmopathy (GO) in 708 patients and 1,178 controls. Results: Patients with GD had significantly lower vitamin D levels compared to controls (55.0 ± 23.2 vs. 87.2 ± 27.6 nmol/L, p < 0.001). In patients with GD (n = 219), there was no association between the levels of vitamin D at diagnosis and free thyroxine (fT4), free triiodothyronine (fT3), thyrotropin receptor antibodies (TRAb), GO at diagnosis, or relapse after terminating treatment with antithyroid drugs. Two SNPs in VDR were associated with GD: rs10735810 (OR = 1.36, 95% CI: 1.02-1.36, p = 0.02) and rs1544410 (OR = 1.47, 95% CI: 1.03-1.47, p = 0.02). There was no difference in the mean vitamin D level between genotypes in either rs10735810 or rs154410. Conclusions: Patients with GD had lower vitamin D levels compared to the general population; however, the vitamin D levels did not affect the laboratory or clinical parameters of GD. SNPs in the VDR influenced the risk of GD through mechanisms other than reducing the vitamin D levels.

19.
World J Surg Oncol ; 16(1): 54, 2018 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-29530065

RESUMO

BACKGROUND: Axillary lymph node status is one of the most important prognostic factors for breast cancer. The aim of this study was to determine predictive factors for metastasis to sentinel node (SN) in primary invasive breast cancer. METHOD: This is a study of 3979 patients with primary breast cancer during 2008-2013 in Malmö and Lund scheduled for surgery and included in the information retrieved from Information Network for Cancer Care (INCA). The final study population included 2552 patients with primary invasive breast cancer. The risk of metastases to SN were examined in relation to potential clinicopathological factors such as age, screening mammography, tumor size, tumor type, histological grade, estrogen status, progesterone status, Her-2 status, multifocality, and lymphovascular invasion. Binary logistic regression was used; adjusted analyses yielded odds ratio (OR) with 95% confidence interval. RESULTS: Tumors detected by mammography screening were less likely to be associated with metastases to SN compared to those not found by mammography screening (0.63; 0.51-0.80). Negative hormonal status for estrogen associated with lower risk for SN metastases compared to tumor with positive estrogen status (0.64; 0.42-0.99). Tumors with a size more than 20 mm had higher risk to metastasize to SN (1.84; 1.47-2.33) compared to tumors less than 20 mm. Multifocality (1.90; 1.45-2.47) and lymphovascular invasion (3.74; 2.66-5.27) were also strong predictive factors for SN metastases. CONCLUSION: SN metastasis is less likely to occur in women with invasive breast cancer diagnosed by screening mammogram. Tumors with negative estrogen status are associated with low risk for SN metastases. Tumors larger than 20 mm, multifocality, or lymphovascular invasion are also factors associated with high risk for SN metastases.


Assuntos
Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Linfonodo Sentinela/patologia , Idoso , Axila , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Feminino , Seguimentos , Humanos , Metástase Linfática , Mamografia , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Suécia/epidemiologia
20.
Breast Cancer Res ; 20(1): 1, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29291743

RESUMO

BACKGROUND: It has been suggested that vitamin D might protect from breast cancer, although studies on levels of vitamin D in association with breast cancer have been inconsistent. Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) to be associated with vitamin D. The aim of this study was to investigate such vitamin D-SNP associations in relation to subsequent breast cancer risk. A first step included verification of these SNPs as determinants of vitamin D levels. METHODS: The Malmö Diet and Cancer Study included 17,035 women in a prospective cohort. Genotyping was performed and was successful in 4058 nonrelated women from this cohort in which 865 were diagnosed with breast cancer. Levels of vitamin D (25-hydroxyvitamin D) were available for 700 of the breast cancer cases and 643 of unaffected control subjects. SNPs previously associated with vitamin D in GWASs were identified. Logistic regression analyses yielding ORs with 95% CIs were performed to investigate selected SNPs in relation to low levels of vitamin D (below median) as well as to the risk of breast cancer. RESULTS: The majority of SNPs previously associated with levels of vitamin D showed a statistically significant association with circulating vitamin D levels. Heterozygotes of one SNP (rs12239582) were found to have a statistically significant association with a low risk of breast cancer (OR 0.82, 95% CI 0.68-0.99), and minor homozygotes of the same SNP were found to have a tendency towards a low risk of being in the group with low vitamin D levels (OR 0.72, 95% CI 0.52-1.00). Results from stratified analyses showed diverse associations with breast cancer risk for a few of the tested SNPs, depending on whether vitamin D level was high or low. CONCLUSIONS: SNPs associated with vitamin D may also be associated with the risk of breast cancer. Even if such a risk is small, the allele frequency of the SNP variants is high, and therefore the population attributable risk could be substantial. It is also possible that vitamin D levels may interact with genomic traits with regard to breast cancer risk.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA