Epidemiology and Surveillance Research

Atlanta, GA, United States

Epidemiology and Surveillance Research

Atlanta, GA, United States

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Spitz M.R.,Baylor College of Medicine | Gorlov I.P.,University of Houston | Dong Q.,University of Houston | Wu X.,University of Houston | And 10 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2012

Background: Tobacco-induced lung cancer is characterized by a deregulated inflammatory microenvironment. Variants in multiple genes in inflammation pathways may contribute to risk of lung cancer. Methods: We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication, and meta-analysis) of inflammation gene variants in ever-smoking lung cancer cases and controls. A discovery set (1,096 cases and 727 controls) and an independent and nonoverlapping internal replication set (1,154 cases and 1,137 controls) were derived from an ongoing case-control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11,737 inflammation pathway single-nucleotide polymorphisms (SNP) and selected nominally significant (P < 0.05) SNPs for internal replication. Results: There were six SNPs that achieved statistical significance (P < 0.05) in the internal replication data set with concordant risk estimates for former smokers and five concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published genome-wide association studies (GWAS) and a case-control study. Two of these variants (a BCL2L14 SNP in former smokers and an SNP in IL2RB in current smokers) were further validated. In risk score analyses, there was a 26% increase in risk with each additional adverse allele whenwecombined the genotyped SNP and the most significant imputed SNP in IL2RB in current smokers and a 36% similar increase in risk for former smokers associated with genotyped and imputed BCL2L14 SNPs. Conclusions/Impact: Before they can be applied for risk prediction efforts, these SNPs should be subject to further external replication and more extensive fine mapping studies. ©2012 AACR.


Genkinger J.M.,Columbia University | Spiegelman D.,Harvard University | Anderson K.E.,University of Minnesota | Bernstein L.,City of Hope National Medical Center | And 27 more authors.
International Journal of Cancer | Year: 2011

Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21-22.9 kg/m2, pancreatic cancer risk was 47% higher (95%CI:23-75%) among obese (BMI ≤yen; 30 kg/m2) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI = 1.09-1.56 comparing BMI ≤yen; 25 kg/m2 to a BMI between 21 and 22.9 kg/m2). Compared to individuals who were not overweight in early adulthood (BMI < 25 kg/m 2) and not obese at baseline (BMI < 30 kg/m2), pancreatic cancer risk was 54% higher (95%CI = 24-93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≤yen; 10 kg/m2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR = 1.35 comparing the highest versus lowest quartile, 95%CI = 1.03-1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer. Copyright © 2010 UICC.


Timofeeva M.N.,International Agency for Research on Cancer | Hung R.J.,Samuel Lunenfeld Research Institute | Rafnar T.,DeCODE Genetics Inc. | Christiani D.C.,Boston University | And 64 more authors.
Human Molecular Genetics | Year: 2012

Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10-16), 6p21 (P = 2.3 × 10-14) and 15q25 (P = 2.2 × 10-63). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16INK4A/p14ARF/CDKN2B/p15INK4B/ANRIL; rs1333040, P = 3.0 × 10-7) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10-8). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cancer. © The Author 2012. Published by Oxford University Press. All rights reserved.


Shi J.,U.S. National Cancer Institute | Chatterjee N.,U.S. National Cancer Institute | Rotunno M.,U.S. National Cancer Institute | Wang Y.,Institute of Cancer Research | And 20 more authors.
Cancer Discovery | Year: 2012

Although lung cancer is largely caused by tobacco smoking, inherited genetic factors play a role in its etiology. Genome-wide association studies in Europeans have only robustly demonstrated 3 polymorphic variations that influence the risk of lung cancer. Tumor heterogeneity may have hampered the detection of association signal when all lung cancer subtypes were analyzed together. In a genome-wide association study of 5,355 European ever-smoker lung cancer patients and 4,344 smoking control subjects, we conducted a pathway-based analysis in lung cancer histologic subtypes with 19,082 single-nucleotide polymorphisms mapping to 917 genes in the HuGE-defined "inflammation" pathway. We identified a susceptibility locus for squamous cell lung carcinoma at 12p13.33 (RAD52, rs6489769) and replicated the association in 3 independent studies totaling 3,359 squamous cell lung carcinoma cases and 9,100 controls (OR = 1.20, Pcombined = 2.3 × 10-8). SIGNIFICA NCE: The combination of pathway-based approaches and information on disease-specific subtypes can improve the identification of cancer susceptibility loci in heterogeneous diseases. © 2012 American Association for Cancer Research.


Leng S.,Lovelace Respiratory Research Institute | Stidley C.A.,University of New Mexico | Liu Y.,Lovelace Respiratory Research Institute | Edlund C.K.,University of Southern California | And 15 more authors.
Cancer Research | Year: 2012

The detection of tumor suppressor gene promoter methylation in sputum-derived exfoliated cells predicts early lung cancer. Here, we identified genetic determinants for this epigenetic process and examined their biologic effects on gene regulation. A two-stage approach involving discovery and replication was used to assess the association between promoter hypermethylation of a 12-gene panel and common variation in 40 genes involved in carcinogen metabolism, regulation of methylation, and DNA damage response in members of the Lovelace Smokers Cohort (N = 1,434). Molecular validation of three identified variants was conducted using primary bronchial epithelial cells. Association of study-wide significance (P < 8.2 × 10 -5) was identified for rs1641511, rs3730859, and rs1883264 in TP53, LIG1, and BIK, respectively. These single-nucleotide polymorphisms (SNP) were significantly associated with altered expression of the corresponding genes in primary bronchial epithelial cells. In addition, rs3730859 in LIG1 was also moderately associated with increased risk for lung cancer among Caucasian smokers. Together, our findings suggest that genetic variation in DNA replication and apoptosis pathways impacts the propensity for gene promoter hypermethylation in the aerodigestive tract of smokers. The incorporation of genetic biomarkers for gene promoter hypermethylation with clinical and somatic markers may improve risk assessment models for lung cancer. ©2011 AACR.


Park Y.,U.S. National Cancer Institute | Wang S.,Beckman Research Institute | Kitahara C.M.,U.S. National Cancer Institute | Moore S.C.,U.S. National Cancer Institute | And 17 more authors.
American Journal of Public Health | Year: 2014

Objectives. We investigated the association between body mass index (BMI) and mortality among Asian Americans. Methods. We pooled data from prospective cohort studies with 20 672 Asian American adults with no baseline cancer or heart disease history. We estimated hazard ratios and 95% confidence intervals (CIs) with Cox proportional hazards models. Results. A high, but not low, BMI was associated with increased risk of total mortality among individuals aged 35 to 69 years. The BMI was not related to total mortality among individuals aged 70 years and older. With a BMI 22.5 to > 25 as the reference category among never-smokers aged 35 to 69 years, the hazard ratios for total mortality were 0.83 (95% CI = 0.47, 1.47) for BMI 15 to > 18.5; 0.91 (95% CI = 0.62, 1.32) for BMI 18.5 to > 20; 1.08 (95% CI = 0.86, 1.36) for BMI 20 to > 22.5; 1.14 (95% CI = 0.90, 1.44) for BMI 25 to > 27.5; 1.13 (95% CI = 0.79, 1.62) for BMI 27.5 to > 30; 1.82 (95% CI = 1.25, 2.64) for BMI 30 to > 35; and 2.09 (95% CI = 1.06, 4.11) for BMI 35 to 50. Higher BMI was also related to increased cardiovascular disease and cancer mortality. Conclusions. High BMI is associated with increased mortality risk among Asian Americans.


PubMed | Epidemiology and Surveillance Research
Type: Journal Article | Journal: Cancer causes & control : CCC | Year: 2010

A family history of pancreatic cancer is associated with increased risk of pancreatic cancer, but uncertainty remains about the magnitude of this association, whether it varies by age or smoking and whether a family history of other cancers may also be associated with increased risk. We examined family history of 14 cancers and pancreatic cancer mortality among ~1.1 million men and women in Cancer Prevention Study-II (CPS-II). CPS-II participants completed a questionnaire at enrollment in 1982. During follow-up through 2006, there were 7,306 pancreatic cancer deaths. A family history of pancreatic cancer in a parent or sibling was associated with pancreatic cancer mortality [multivariable adjusted rate ratio (RR) = 1.66, 95% confidence interval (CI) 1.43-1.94]. This association was stronger among participants aged under 60 (RR = 2.89, 95% CI 1.67-5.02) than among participants aged 60 or older (RR = 1.61, 95% CI 1.37-1.88). Weaker associations were observed for family history of stomach cancer (RR = 1.23, 95% CI 1.11-1.37), liver cancer (RR = 1.25, 95% CI 1.10-1.43), and colorectal cancer (RR = 1.12, 95% CI 1.01-1.23). Results from this large prospective study indicate family history of pancreatic cancer is associated with a moderate increase in risk of pancreatic cancer, and also identify associations with the family history of certain other cancers which may be useful in generating hypotheses about shared risk factors.


Kim D.-H.,Hallym University | Smith-Warner S.A.,Harvard University | Spiegelman D.,Harvard University | Yaun S.-S.,Harvard University | And 23 more authors.
Cancer Causes and Control | Year: 2010

Objective: Studies of folate intake and colorectal cancer risk have been inconsistent. We examined the relation with colon cancer risk in a series of 13 prospective studies. Methods: Study-and sex-specific relative risks (RRs) were estimated from the primary data using Cox proportional hazards models and then pooled using a random-effects model. Results: Among 725,134 participants, 5,720 incident colon cancers were diagnosed during follow-up. The pooled multivariate RRs (95% confidence interval [CI]) comparing the highest vs. lowest quintile of intake were 0.92 (95% CI 0.84-1.00, p-value, test for between-studies heterogeneity = 0.85) for dietary folate and 0.85 (95% CI 0.77-0.95, p-value, test for between-studies heterogeneity = 0.42) for total folate. Results for total folate intake were similar in analyses using absolute intake cutpoints (pooled multivariate RR = 0.87, 95% CI 0.78-0.98, comparing ≥560 mcg/days vs. <240 mcg/days, p-value, test for trend = 0.009). When analyzed as a continuous variable, a 2% risk reduction (95% CI 0-3%) was estimated for every 100 μg/day increase in total folate intake. Conclusion: These data support the hypothesis that higher folate intake is modestly associated with reduced risk of colon cancer. © 2010 Springer Science+Business Media B.V.


Thun M.,Epidemiology and Surveillance Research | Thun M.,University of Queensland | Peto R.,University of Oxford | Boreham J.,University of Oxford | Lopez A.D.,University of Queensland
Tobacco Control | Year: 2012

Objectives A four-stage model of the cigarette epidemic was proposed in 1994 to communicate the long delay between the widespread uptake of cigarette smoking and its full effects on mortality, as had been experienced in economically developed countries where cigarette smoking became entrenched decades earlier in men than in women. In the present work, the question of whether qualitative predictions from the model have matched recent trends in smoking and deaths from smoking in countries at various levels of economic development is assessed, and possible projections to the year 2025 are considered. Methods The proportion of all deaths attributed to tobacco was estimated indirectly for 41 high-resource and medium-resource countries from 1950 to the most recent year for which data were available, generally about 2005e2009. The trends in tobacco-attributed mortality in later middle age were then projected forward to 2025, based on recent trends in tobacco-attributed mortality in early middle age. Results In developed countries the prevalence of smoking has continued to decrease in both sexes, although the rate of decrease has slowed and is less than that predicted by the original version of the model. Over the past 20 years the proportionate contribution of smoking to all deaths has decreased in men while continuing to increase or plateau among women. Although the proportion of all deaths at ages 35e69 that are attributed to smoking is still generally greater in men than in women, the male and female proportions are converging and will probably cross over in some high resource countries. Projections through to 2025 suggest that male and female smoking prevalence and smoking- attributed mortality will decrease in parallel in most developed countries towards lower limits that are not yet defined. In developing countries the model seems generally applicable to men but cannot predict whether or when women will begin smoking in large numbers. Modified criteria that describe the stages of the epidemic separately for men and women would be more generalisable to developing countries. Conclusions The four-stage model of the cigarette epidemic still provides a reasonably useful description in many developed countries. Its relevance to developing countries could be improved by describing the stages of the epidemic separately for men and women.


Rock C.L.,University of California at San Diego | Doyle C.,American Physical Society | Demark-Wahnefried W.,University of Alabama at Birmingham | Meyerhardt J.,Dana-Farber Cancer Institute | And 8 more authors.
CA Cancer Journal for Clinicians | Year: 2012

Cancer survivors are often highly motivated to seek information about food choices, physical activity, and dietary supplements to improve their treatment outcomes, quality of life, and overall survival. To address these concerns, the American Cancer Society (ACS) convened a group of experts in nutrition, physical activity, and cancer survivorship to evaluate the scientific evidence and best clinical practices related to optimal nutrition and physical activity after the diagnosis of cancer. This report summarizes their findings and is intended to present health care providers with the best possible information with which to help cancer survivors and their families make informed choices related to nutrition and physical activity. The report discusses nutrition and physical activity guidelines during the continuum of cancer care, briefly highlighting important issues during cancer treatment and for patients with advanced cancer, but focusing largely on the needs of the population of individuals who are disease free or who have stable disease following their recovery from treatment. It also discusses select nutrition and physical activity issues such as body weight, food choices, food safety, and dietary supplements; issues related to selected cancer sites; and common questions about diet, physical activity, and cancer survivorship. © 2012 American Cancer Society.

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