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1.
Gerontology ; : 1-7, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600755

RESUMO

BACKGROUND: Studies show that regular moderate to vigorous physical activity is associated with a lower risk of cardiovascular disease, certain cancers, and premature death, but few studies have examined associations of light-intensity physical activity (LPA) and mortality, especially among older adults. OBJECTIVES: The aim of this study was to investigate the association of LPA with the risks of death from all causes, cancer, cardiovascular diseases, and respiratory diseases among older adults in the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). METHODS: Analyses included 123,232 participants in CPS-II NC, among whom 46,829 died during follow-up (1993-2014). Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for self-reported leisure time LPA associated with mortality. RESULTS: Engaging in little or no LPA (<3 metabolic equivalent [MET]-h/week) was associated with a 16% higher risk of all-cause mortality (HR 1.16, 95% CI 1.12-1.20) compared to engaging in some LPA (3 to <9 MET-h/week) after adjusting for moderate to vigorous physical activity. However, there was no evidence of a dose-response relationship. A statistically significant interaction with age suggested that more LPA was associated with a lower risk of respiratory disease mortality only among participants aged ≥70 years (21+ vs. 3 to <9 MET-h/week, HR 0.78, 95% CI 0.66-0.91; pint = 0.003). CONCLUSIONS: In this prospective study of older adults, accumulating little/no leisure time LPA was associated with a higher risk of mortality. It is of substantial public health value to demonstrate the potential benefits of engaging in any activity, even if light in intensity, among older adults given the aging US population.

2.
Am J Epidemiol ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602476

RESUMO

Higher body mass index (BMI) is associated with increased risk of pancreatic cancer in epidemiologic studies but BMI has usually been assessed at older ages, potentially underestimating the full impact of excess weight. We examined the association between BMI and pancreatic cancer mortality among 963,317 adults aged 30-89 years at enrollment into Cancer Prevention Study-II in 1982. During follow-up through 2014, 8,354 participants died of pancreatic cancer. Hazard ratios (HRs) per 5 BMI-units, calculated using proportional hazards regression, declined steadily with age at BMI assessment, from 1.25 (95% confidence interval (CI) 1.18, 1.33) in those aged 30-49 at enrollment to 1.13 (95% CI 1.02, 1.26) in those aged 70-89 (p-trend=0.005). Based on a HR of 1.25 per 5 BMI-units at age 45, we estimate 28% of US pancreatic cancer deaths in those born from 1970-74 will be attributable to BMI≥25, nearly twice the equivalent proportion in those born in the 1930s, a birth cohort with much lower BMI in middle age. These results suggest BMI before age 50 is more strongly associated with pancreatic cancer risk than BMI at older ages and underscore the importance of avoiding excess weight gain before middle age for preventing this highly fatal cancer.

3.
Eur Urol Oncol ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31378665

RESUMO

BACKGROUND: Little is known about the underlying molecular mechanisms of prostate cancer, especially advanced and fatal prostate cancer. OBJECTIVE: To examine associations of prediagnostic plasma metabolomic profiles with advanced and fatal prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: In a case-cohort study of the Cancer Prevention Study-II Nutrition Cohort, of 14 210 cancer-free men with a blood sample in 1998-2001, 129 were diagnosed with advanced prostate cancer (T3-T4 or N1 or M1) through June 2013 and 112 died from prostate cancer through December 2014. Plasma samples from advanced and fatal cases, and a randomly selected subcohort of 347 men were metabolically profiled using untargeted mass spectroscopy-based platforms. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prentice-weighted Cox proportional hazards regression models were used to assess associations of 699 known metabolites with advanced and fatal prostate cancer. RESULTS AND LIMITATIONS: Two metabolites derived from fatty acid metabolism (ethylmalonate and butyrylcarnitine), aspartate, sphingomyelin (d18:1/18:0), and two γ-glutamyl amino acids (γ-glutamylmethionine and γ-glutamylglutamine) were statistically significantly associated (false discovery rate <0.2) with fatal prostate cancer. One standard deviation (SD) increase in each γ-glutamyl amino acid was associated with 34-38% decreased risk, whereas one SD increase in each of the other metabolites was associated with 45-53% increased risk. A metabolic risk score based on four of these metabolites (excluding butyrylcarnitine and γ-glutamylglutamine, which were not independent predictors) was strongly associated with fatal prostate cancer (relative risk per SD: 2.72, 95% confidence interval: 2.05-3.60). No metabolites were statistically significantly associated with advanced prostate cancer. These results were observational and may not be causal. CONCLUSIONS: These findings identified metabolic pathways that are altered in the development of fatal prostate cancer. Further research into these pathways may provide insights into the etiology of fatal prostate cancer. PATIENT SUMMARY: In a large follow-up study of cancer-free men, those with a certain metabolomic profile had a higher risk of dying from prostate cancer.

4.
Sci Rep ; 9(1): 12524, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467304

RESUMO

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

5.
Breast Cancer Res Treat ; 177(3): 679-689, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31264062

RESUMO

PURPOSE: In a screened population, breast cancer-specific mortality is lower for screen-detected versus symptom-detected breast cancers; however, it is unclear whether this association varies by follow-up time and/or tumor characteristics. To further understand the prognostic utility of mode of detection, we examined its association with breast cancer-specific mortality, overall and by follow-up time, estrogen receptor status, tumor size, and grade. METHODS: In the Cancer Prevention Study-II Nutrition Cohort, 3975 routinely screened women were diagnosed with invasive breast cancer (1992-2015). Among 2686 screen-detected and 1289 symptom-detected breast cancers, 206 and 209 breast cancer deaths, respectively, occurred up to 24 years post diagnosis. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox proportional hazard regression models. RESULTS: Controlling for prognostic factors, symptom detection was associated with higher risk of breast cancer-specific death up to 5 years after diagnosis (HR≤5years = 1.88, 95% CI 1.21-2.91) this association was attenuated in subsequent follow-up (HR>5years = 1.26, 95% CI 0.98-1.63). Within tumor characteristic strata, there was a 1.3-2.7-fold higher risk of breast cancer death associated with symptom-detected cancers ≤ 5 years of follow-up, although associations were only significant for women with tumors < 2 cm (HR≤5years = 2.42, 95% CI 1.19-4.93) and for women with grade 1 or 2 tumors (HR≤5years = 2.72, 95% CI 1.33-5.57). In subsequent follow-up, associations were closer to the null. CONCLUSIONS: Screen detection is a powerful prognostic factor for short-term survival. Among women who survived at least 5 years after breast cancer diagnosis, other clinical factors may be more predictive of breast cancer survival.

6.
Cancer Epidemiol Biomarkers Prev ; 28(9): 1489-1494, 2019 Sep.
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.

7.
Eur J Nutr ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31240448

RESUMO

PURPOSE: Evidence supports a role of whole grains in colorectal cancer (CRC) prevention, but the association between gluten intake and CRC risk in healthy populations is unclear. We examined the association of grain and gluten intake with risk of CRC overall and by subsite among Cancer Prevention Study-II Nutrition Cohort participants. METHODS: In 1999, 50,118 men and 62,031 women completed food frequency questionnaires assessing grain intake. Gluten intake was estimated using the protein content of grain products. Multivariable-adjusted hazards ratio (HR) and 95% confidence interval (CI) of CRC risk were estimated using Cox proportional hazards regression. RESULTS: During follow-up through 2013, 1742 verified CRC cases occurred. For the highest vs. lowest quintiles of whole grain intake, HRs (95% CIs) of CRC risk were 0.77 (0.61-0.97; P trend = 0.03) among men and 1.10 (95% CI 0.88-1.36; P trend = 0.14) among women (P interaction by sex = 0.01). Men in the highest vs. lowest quintile of whole grain intake had a 43% lower risk of rectal cancer (HR = 0.57, 95% CI 0.35-0.93, P trend = 0.04). Gluten intake was not associated with CRC risk overall (HR = 1.10, 95% CI 0.93-1.32, P trend = 0.10), but was associated with risk of proximal colon cancer among men and women, combined (HR = 1.37, 95% CI 1.07-1.75, quintile 5 vs. 1, P trend = 0.001) and separately. Refined grains and grain-based sweets were not associated with CRC risk. CONCLUSIONS: We found that higher whole grain intake was associated with lower CRC risk among older US men, but not women. The positive association of gluten intake with the risk of proximal colon cancer deserves further study.

8.
J Natl Cancer Inst ; 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127946

RESUMO

BACKGROUND: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. METHODS: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random effects meta-analysis produced summary estimates. All statistical tests were two-sided. RESULTS: Over a period of 38,369,156 person-years of follow-up, 1,391 gallbladder, 758 intrahepatic bile duct, 1,208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (e.g., current versus never smokers hazard ratio [HR] = 1.69, 95% confidence interval [CI] = 1.34 to 2.13 and 2.22, 95%CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all P-trend<0.01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (e.g., >40 cigarettes/day versus never smokers HR = 2.15, 95%CI: 1.15 to 4.00; P-trend=0.001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming ≥5 versus 0 drinks/day (HR = 2.35, 95%CI = 1.46 to 3.78; P-trend=0.04). There was evidence of statistical heterogeneity between several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. CONCLUSIONS: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.

9.
Cancer Res ; 79(15): 3973-3982, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31113819

RESUMO

Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.

10.
Br J Haematol ; 186(2): 243-254, 2019 Jul.
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.

11.
Am J Prev Med ; 56(5): 736-741, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30905483

RESUMO

INTRODUCTION: Excess sitting is a risk factor for early mortality. This may be resulting, at least in part, from the displacement of physical activity with sedentary behaviors. The purpose of this observational study was to examine the mortality risk reductions associated with replacing 30minutes/day sitting for an equivalent duration of light or moderate to vigorous physical activity (MVPA). METHODS: Participants included 37,924 men and 54,617 women in the Cancer Prevention Study-II Nutrition Cohort, of which 14,415 men and 13,358 women died during follow-up (1999-2014). An isotemporal substitution approach to the Cox proportional hazards regression model was used to estimate adjusted hazard ratios and 95% CIs for mortality associated with the substitution of 30minutes/day self-reported sitting for light physical activity or MVPA. Analyses were conducted in 2018. RESULTS: Among the least active participants (≤17minutes/day MVPA), the replacement of 30minutes/day sitting with light physical activity was associated with a 14% mortality risk reduction (hazard ratio=0.86, 95% CI=0.81, 0.89) and replacement with MVPA was associated with a 45% mortality risk reduction (hazard ratio=0.55, 95% CI=0.47, 0.62). Similar associations were seen among moderately active participants (light physical activity replacement, hazard ratio=0.94, 95% CI=0.91, 0.97; MVPA replacement, hazard ratio=0.83, 95% CI=0.76, 0.88). However, for the most active (MVPA >38 minutes/day), substitution of sitting time with light physical activity or MVPA was not associated with a reduction in mortality risk (hazard ratio=1.00, 95% CI=0.97, 1.03, and hazard ratio=0.99, 95% CI=0.95, 1.02, respectively). CONCLUSIONS: These findings suggest that the replacement of modest amounts of sitting time with even light physical activity may have the potential to reduce the risk of premature death among less active adults.

12.
Int J Cancer ; 145(10): 2647-2660, 2019 Nov 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.

15.
CA Cancer J Clin ; 69(2): 88-112, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30548482

RESUMO

The prevalence of excess body weight and the associated cancer burden have been rising over the past several decades globally. Between 1975 and 2016, the prevalence of excess body weight in adults-defined as a body mass index (BMI) ≥ 25 kg/m2 -increased from nearly 21% in men and 24% in women to approximately 40% in both sexes. Notably, the prevalence of obesity (BMI ≥ 30 kg/m2 ) quadrupled in men, from 3% to 12%, and more than doubled in women, from 7% to 16%. This change, combined with population growth, resulted in a more than 6-fold increase in the number of obese adults, from 100 to 671 million. The largest absolute increase in obesity occurred among men and boys in high-income Western countries and among women and girls in Central Asia, the Middle East, and North Africa. The simultaneous rise in excess body weight in almost all countries is thought to be driven largely by changes in the global food system, which promotes energy-dense, nutrient-poor foods, alongside reduced opportunities for physical activity. In 2012, excess body weight accounted for approximately 3.9% of all cancers (544,300 cases) with proportion varying from less than 1% in low-income countries to 7% or 8% in some high-income Western countries and in Middle Eastern and Northern African countries. The attributable burden by sex was higher for women (368,500 cases) than for men (175,800 cases). Given the pandemic proportion of excess body weight in high-income countries and the increasing prevalence in low- and middle-income countries, the global cancer burden attributable to this condition is likely to increase in the future. There is emerging consensus on opportunities for obesity control through the multisectoral coordinated implementation of core policy actions to promote an environment conducive to a healthy diet and active living. The rapid increase in both the prevalence of excess body weight and the associated cancer burden highlights the need for a rejuvenated focus on identifying, implementing, and evaluating interventions to prevent and control excess body weight.

16.
Int J Cancer ; 145(1): 58-69, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561796

RESUMO

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.

17.
JAMA Oncol ; 5(3): 384-392, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30589925

RESUMO

Importance: Excess body weight (EBW) is an established cause of cancer. Despite variations in the prevalence of EBW among US states, there is little information on the EBW-related cancer burden by state; this information would be useful for setting priorities for cancer-control initiatives. Objective: To calculate the population attributable fraction (PAF) of incident cancer cases attributable to EBW among adults 30 years or older in 2011 to 2015 in all 50 states and the District of Columbia. Design, Setting, and Participants: State-level, self-reported body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) data from the Behavioral Risk Factor Surveillance System were adjusted by sex, age, race/ethnicity, and education using objectively measured BMI values from the National Health and Nutrition Examination Survey. Age- and sex-specific cancer incidence data by state were obtained from the US Cancer Statistics database. All analyses were performed between February 15, 2018, and July 17, 2018. Main Outcomes and Measures: Sex-, age-, and state-specific adjusted prevalence estimates for 4 high BMI categories and corresponding relative risks from large-scale pooled analyses or meta-analyses were used to compute the PAFs for each US state for esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colorectum, liver, gallbladder, pancreas, female breast, corpus uteri, ovary, kidney and renal pelvis, and thyroid. Results: Each year, an estimated 37 670 cancer cases in men (4.7% of all cancer cases excluding nonmelanoma skin cancers) and 74 690 cancer cases in women (9.6%) 30 years or older in the United States were attributable to EBW from 2011 to 2015. In both men and women, there was at least a 1.5-fold difference in the proportions of cancers attributable to EBW between states with the highest and lowest PAFs. Among men, the PAF ranged from 3.9% (95% CI, 3.6%-4.3%) in Montana to 6.0% (95% CI, 5.6%-6.4%) in Texas. The PAF for women was approximately twice as high as for men, ranging from 7.1% (95% CI, 6.7%-7.6%) in Hawaii to 11.4% (95% CI, 10.7%-12.2%) in the District of Columbia. The largest PAFs were found mostly in southern and midwestern states, as well as Alaska and the District of Columbia. Conclusions and Relevance: The proportion of cancers attributable to EBW varies among states, but EBW accounts for at least 1 in 17 of all incident cancers in each state. Broad implementation of known community- and individual-level interventions is needed to reduce access to and marketing of unhealthy foods (eg, through a tax on sugary drinks) and to promote and increase access to healthy foods and physical activity, as well as preventive care.

19.
Genome Med ; 10(1): 99, 2018 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-30583724

RESUMO

BACKGROUND: Prior research has established that the prevalence of pathogenic/likely pathogenic (P/LP) variants across all of the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes is approximately 0.8-5%. We investigated the prevalence of P/LP variants in the 24 ACMG SF v2.0 cancer genes in a family-based cancer research cohort (n = 1173) and in cancer-free ethnicity-matched controls (n = 982). METHODS: We used InterVar to classify variants and subsequently conducted a manual review to further examine variants of unknown significance (VUS). RESULTS: In the 24 genes on the ACMG SF v2.0 list associated with a cancer phenotype, we observed 8 P/LP unique variants (8 individuals; 0.8%) in controls and 11 P/LP unique variants (14 individuals; 1.2%) in cases, a non-significant difference. We reviewed 115 VUS. The median estimated per-variant review time required was 30 min; the first variant within a gene took significantly (p = 0.0009) longer to review (median = 60 min) compared with subsequent variants (median = 30 min). The concordance rate was 83.3% for the variants examined by two reviewers. CONCLUSION: The 115 VUS required database and literature review, a time- and labor-intensive process hampered by the difficulty in interpreting conflicting P/LP determinations. By rigorously investigating the 24 ACMG SF v2.0 cancer genes, our work establishes a benchmark P/LP variant prevalence rate in a familial cancer cohort and controls.


Assuntos
Genes Neoplásicos/genética , Predisposição Genética para Doença , Mutação , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Coortes , Análise Mutacional de DNA , Grupos Étnicos , Feminino , Humanos , Masculino
20.
Artigo em Inglês | MEDLINE | ID: mdl-30420439

RESUMO

BACKGROUND: Acrylamide, an industrial chemical and probable human carcinogen, can be formed in primarily carbohydrate-containing foods during high heat cooking or processing. Most epidemiological studies show no associations of dietary acrylamide intake with most cancer outcomes, but limited prospective evidence suggests a positive association with renal cell carcinoma (RCC). METHODS: In 1999, 102,154 men and women from the Cancer Prevention Study-II Nutrition Cohort completed a questionnaire on diet, lifestyle and cancer risk factors and were followed through June 30, 2013. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between estimated dietary acrylamide intake and risk of RCC. RESULTS: After 1,137,441 person-years of follow-up, 412 cases of invasive RCC occurred. In multivariable adjusted models, there was no association between acrylamide intake and risk of RCC (HR=1.09, 95% CI 0.82-1.43) for the highest vs. lowest quartile of intake. Associations were not modified by sex or smoking history. CONCLUSIONS: We found no associations between dietary acrylamide exposure and risk of invasive RCC. IMPACT: Findings from this large, prospective analysis do not support a positive association between higher dietary acrylamide intake and RCC risk.

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