R N Hoover

National Cancer Institute (USA), Maryland, United States

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Publications (468)4173.62 Total impact

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    ABSTRACT: The purpose of this study was to compare longitudinally sampled maternal angiogenic proteins between singleton and twin pregnancies. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble endoglin (sEng) from healthy pregnant women were quantified at 10, 18, 26 and 35 weeks' gestation (n=91), and during the third trimester (31-39 weeks) and at delivery (33-41 weeks; n=41). Geometric means and 95% confidence intervals were calculated for gestational age adjusted angiogenic protein concentrations and compared between matched twin and singleton pregnancies. Maternal sFlt-1 concentrations and the sFlt-1/PlGF ratio were higher in twins than singletons across pregnancy and at delivery, with the greatest differences at week 35 [sFlt-1: 36916 vs. 10151 pg/mL; p<0.0001; sFlt-1/PlGF: 168.4 vs. 29.0; p<0.0001]. Maternal concentrations of s-endoglin also were higher in the third trimester and delivery. Maternal PlGF concentrations were lower in twin than singleton pregnancies at week 35 only [219.2 vs. 350.2 pg/mL; p<0.0001]. Placental weight appeared to be inversely correlated with maternal sFlt-1/PlGF ratio at the end of the pregnancy in both twins and singletons. Higher maternal anti-angiogenic proteins in twin than singleton pregnancies does not appear to be due to greater placental mass in the former, and may be one explanation for the increased risk of preeclampsia in women carrying multiple gestations. Determining whether women with a history of multiple gestations have an altered cardiovascular disease and breast cancer risk, like those with a history of preeclampsia, is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.
    American journal of obstetrics and gynecology. 11/2014;
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    ABSTRACT: IntroductionEarlier menarche is related to subsequent breast cancer risk, yet international differences in the age and tempo of other pubertal milestones and their relationships with body mass index (BMI) are not firmly established in populations at differing risk for breast cancer. We compared age and tempo of adrenarche, thelarche, pubarche, and menarche in a migrant study of Bangladeshi girls to the United Kingdom (UK) and assessed whether differences by migration were explained by differences in BMI.Methods Included were groups of Bangladeshi (n =168, British-Bangladeshi (n =174) and white British (n =54) girls, aged 5 to 16 years. Interviewer-administered questionnaires obtained pubertal staging; height and weight were measured. Salivary dehydroepiandrosterone-sulfate concentrations >400 pg/ml defined adrenarche. Median ages of pubertal milestones and hazard ratios (HR) with 95% confidence intervals (CI) were estimated from Weibull survival models.ResultsIn all three groups, adrenarche occurred earliest, followed by thelarche, pubarche, and finally menarche. Neither median age at adrenarche (Bangladeshi = 7.2, British-Bangladeshi = 7.4, white British = 7.1; P-trend = 0.70) nor at menarche (Bangladeshi = 12.5, British-Bangladeshi = 12.1, white British = 12.6; P-trend = 0.70) differed across groups. In contrast, median age at thelarche (Bangladeshi = 10.7, British-Bangladeshi = 9.6, white British = 8.7; P-trend <0.01) occurred earlier among girls living in the UK. Compared with Bangladeshi girls, HRs (95% CI) for earlier thelarche were 1.6 (1.1 to 2.4) for British-Bangladeshi girls and 2.6 (1.5 to 4.4) for white British girls (P-trend <0.01), but were attenuated after adjustment for BMI (British-Bangladeshi = 1.1 (0.7 to 1.8), white British = 1.7(1.0 to 3.1); P-trend =0.20).Conclusions Thelarche occurred earlier, but puberty progressed slower with increasing exposure to the UK environment; differences were partially explained by greater BMI. The growth-environment might account for much of the ethnic differences in pubertal development observed across and within countries.
    Breast cancer research: BCR 11/2014; 16(6):469. · 5.87 Impact Factor
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    ABSTRACT: No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS).
    European urology. 09/2014;
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    ABSTRACT: Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.
    American journal of epidemiology. 09/2014;
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    ABSTRACT: Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
    Nature genetics. 09/2014;
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    ABSTRACT: Background: The combined action of androgens and estrogens-specifically their balance-may play a role in prostate carcinogenesis but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer. Methods: In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort we measured serum estrone, estradiol and 13 estrogen metabolites, in the 2-, 4, or 16-hydroxylation pathways, using a liquid chromatography-tandem mass spectrometry assay. Cases (n=195) were non-Hispanic white men aged 55-70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7). Controls (n=195) were non-Hispanic white men without prostate cancer who were frequency-matched to cases by age and year at blood draw, time since baseline screen. Only men with serum testosterone and sex hormone-binding globulin measured previously were eligible. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). Results: Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR4th quartile vs. 1st =0.27, 95% CI 0.12-0.59, p trend=0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st =2.44, 95% CI 1.34-4.45, p trend=0.001). Estradiol, estrone and estrogen metabolites were unrelated to risk. Conclusions: Our findings suggest that sex steroid hormones, specifically the estrogen-androgen balance, may be important in the development of aggressive prostate cancer. Impact: Improved understanding of the hormonal etiology of prostate cancer is critical for prevention and therapeutic interventions.
    09/2014;
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    ABSTRACT: We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
    Nature genetics. 08/2014;
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    ABSTRACT: Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
    Human Molecular Genetics 07/2014; · 7.69 Impact Factor
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    ABSTRACT: Background: With over 13 million cancer survivors in the United States today, second cancers are of rapidly growing importance. However, data on non-treatment risk factors for second cancers are sparse. We explored the feasibility of pooling data from cohort studies of cancer incidence to investigate second cancer etiology. Methods: We combined data from five prospective studies including more than 800,000 individuals. We compared study designs and populations; evaluated availability of and ability to harmonize risk factor data; compared incidence and survival for common first primary malignancies and incidence of second primary malignancies; and estimated sample size requirements. Results: Overall, 96,513 incident, first primary malignancies were diagnosed during 1985-2009. Incidence rates and survival following the first primary varied among the cohorts, but most of the heterogeneity could be explained by characteristics of the study populations (age, sex, smoking, and screening rates). 7,890 second primary cancers (excluding original primary site) were identified, yielding sufficient statistical power (≥80%) for detecting modest associations with risk of all second cancers among survivors of common first primary malignancies (e.g., colorectal cancer); however, there were insufficient events for studying survivors of rarer cancers or identifying risk factors for specific second cancers. Conclusion: Pooling data from cohort studies to investigate non-treatment risk factors for second primary cancers appears feasible but there are important methodological issues - some of which are barriers to specific research questions - that require special attention. Impact: Increased understanding of non-treatment risk factors for second cancers will provide valuable prevention and surveillance information.
    Cancer Epidemiology Biomarkers &amp Prevention 05/2014; · 4.56 Impact Factor
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    ABSTRACT: We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (Pinteraction = 8.84 × 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
    Human Molecular Genetics 05/2014; · 7.69 Impact Factor
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    ABSTRACT: Reasons for the high rates of prostate cancer in African Americans are unknown; both genetic and lifestyle factors have been implicated. A better understanding of prostate cancer rates in West Africans would help clarify why African Americans have such high rates, since African Americans share genetic ancestry with West Africans yet have very different lifestyles and screening practices. To estimate prostate cancer burden in West Africans, we conducted a population-based screening study with biopsy confirmation in Ghana. We randomly selected 1,037 healthy men aged 50-74 from Accra, Ghana for prostate cancer screening with prostate specific antigen (PSA) testing and digital rectal examination (DRE). Men who had a positive screen (DRE+ or PSA>2.5 ng/ml) underwent transrectal ultrasound (TRUS)-guided biopsies. Of the 1,037 men, 154 (14.9%) had a positive DRE and 272 (26.2%) had a PSA>2.5 ng/ml (166 had a PSA>4.0 ng/ml). In total, 352 (33.9%) men had a positive screen by PSA or DRE, and 307 (87%) had a biopsy. Of these, 73 were confirmed to have prostate cancer, yielding a 7.0% screen-detected prevalence of prostate cancer (65 cases, 5.8% with a PSA>4.0 ng/ml). In this relatively unscreened population in Africa, the screen-detected prostate cancer prevalence is high, suggesting a possible role of genetics in both prostate cancer etiology and the disparity in prostate cancer risk between African Americans and Caucasian Americans. Further studies are needed to confirm the high prostate cancer burden in Africans and the role of genetics in prostate cancer etiology.
    The Journal of urology 04/2014; · 3.75 Impact Factor
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    ABSTRACT: 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. (Am J Public Health. Published online ahead of print January 16, 2014: e1-e6. doi:10.2105/AJPH.2013.301573).
    American Journal of Public Health 01/2014; · 3.93 Impact Factor
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    ABSTRACT: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM. We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred. The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls. Among the cases, we found that 8 of the 47 SNPs were significantly associated (p<0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p<0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only. Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction.
    European Urology 01/2014; · 10.48 Impact Factor
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    ABSTRACT: Adrenarche is a key early life event that marks middle childhood at approximately 7 years of age. Earlier work with British-Bangladeshi migrant women suggested that environmental conditions experienced before adrenarche influence adult reproductive function. We therefore investigated whether Bangladeshi children who migrate to the United Kingdom (UK) reach adrenarche earlier than non-migrants in Bangladesh or the United Kingdom.
    PLoS ONE 01/2014; 9(10):e109200. · 3.53 Impact Factor
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    ABSTRACT: An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly. We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation. In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ≥75 years (ptrend = 0.03), while no trend was seen for PDE5I (ptrend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11). In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.
    PLoS ONE 01/2014; 9(1):e85805. · 3.53 Impact Factor
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    ABSTRACT: Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-). Compared with ER-positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER-negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5×10(-8)) to perform a secondary analysis of an ER-negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER- cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER-GWAS were significant at the adjusted threshold. 186 variants were associated with ER- breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3×10(-4). None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a "pleiotropic approach".
    PLoS ONE 01/2014; 9(2):e85955. · 3.53 Impact Factor
  • American Journal of Industrial Medicine 01/2014; 57(4). · 1.97 Impact Factor
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    ABSTRACT: Background. We investigated perinatal factors in relation to bone cancer subtypes, osteosarcoma (OS), Ewing Sarcoma (ES) and chondrosarcoma (CS). Materials and methods. All cases in Norway (1970-2009), Sweden (1974-2009) and Denmark (1980-2010) < 43 years were included (n = 914); 10 controls per case were selected from birth registries (which provided information on pregnancies) matched on birth country, sex and birth year (n = 9140). Unconditional logistic regression models including sex and birth year were used to compute relative risk (RR) and 95% confidence intervals (CI). Results. Higher maternal education was associated with a 40% increase in OS risk (95% CI 1-93%). The RR for OS was 3.22 (95% CI 1.37-7.59) comparing offspring of hypertensive mothers with those of mothers with a normotensive pregnancy, and Cesarean section was associated with a 29% risk reduction (95% CI 0-50%). When gestational age, birth weight and birth length were assessed simultaneously, there were no associations with any of the bone tumor subtypes. Conclusion. These results provided little evidence of an important role of pregnancy factors in the etiology of bone cancers. Higher maternal education may be associated with factors, possibly early nutrition or other correlates of socioeconomic status, that increase OS risk in offspring. The elevated OS risk associated with gestational hypertension and reduced risk associated with Cesarean section warrant replication.
    Acta oncologica (Stockholm, Sweden) 12/2013; · 2.27 Impact Factor
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    ABSTRACT: Background: Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. Methods: We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the U.S. and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk-associated single-nucleotide polymorphisms (SNPs). We also examined the associations between 13 diabetes risk-associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted logistic regression models. Results: We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR=0.58, 95% CI: 0.40-0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological sub-type. We did not observe any significant per-allele trends among the 13 diabetes-related SNPs examined in relation to glioma risk. Conclusion: These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association. Impact: These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma.
    Cancer Epidemiology Biomarkers &amp Prevention 11/2013; · 4.56 Impact Factor
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    ABSTRACT: Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (≥7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci.
    Human Genetics 11/2013; · 4.63 Impact Factor

Publication Stats

24k Citations
4,173.62 Total Impact Points

Institutions

  • 1981–2014
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Cancer Prevention Fellowship Program
      • • Laboratory of Translational Genomics
      • • Epidemiology and Biostatistics
      • • Occupational and Environmental Epidemiology
      Maryland, United States
  • 1979–2014
    • National Institutes of Health
      • • Division of Cancer Epidemiology and Genetics
      • • Branch of Hormonal and Reproductive Epidemiology
      • • Branch of Bio-statistics
      • • Laboratory of Human Carcinogenesis
      • • Branch of Occupational and Environmental Epidemiology
      Maryland, United States
  • 2013
    • Institute of Cancer Research
      Londinium, England, United Kingdom
  • 2010–2013
    • Imperial College London
      • • Department of Epidemiology and Biostatistics
      • • Department of Primary Care and Public Health
      London, ENG, United Kingdom
    • University of Cambridge
      • Department of Oncology
      Cambridge, ENG, United Kingdom
    • Tufts Medical Center
      • Department of Obstetrics and Gynecology
      Boston, Massachusetts, United States
    • Mayo Clinic - Rochester
      • Department of Health Science Research
      Rochester, MN, United States
  • 2001–2013
    • Harvard Medical School
      • • Division of Nutrition
      • • Department of Medicine
      Boston, MA, United States
    • Boston University
      • • Slone Epidemiology Center
      • • Department of Epidemiology
      Boston, MA, United States
  • 2012
    • American Cancer Society
      • Epidemiology Research Program
      Atlanta, GA, United States
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 1990–2012
    • NCI-Frederick
      Maryland, United States
    • Walter Reed Army Institute of Research
      Silver Spring, Maryland, United States
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden
  • 2009–2010
    • Netherlands Cancer Institute
      Amsterdamo, North Holland, Netherlands
    • Geisel School of Medicine at Dartmouth
      • Department of Community and Family Medicine
      Hanover, New Hampshire, United States
    • Oslo University Hospital
      Kristiania (historical), Oslo County, Norway
  • 2006–2010
    • Harvard University
      • Department of Epidemiology
      Boston, MA, United States
    • United States Geological Survey
      • New Hampshire-Vermont Water Science Center
      Reston, Virginia, United States
    • George Washington University
      • Department of Epidemiology and Biostatistics
      Washington, D. C., DC, United States
    • University at Buffalo, The State University of New York
      • Department of Social and Preventive Medicine
      Buffalo, NY, United States
  • 2003–2008
    • Dartmouth College
      • • Department of Community and Family Medicine
      • • Dartmouth-Hitchcock Medical Center
      Hanover, NH, United States
  • 2007
    • Dartmouth–Hitchcock Medical Center
      Lebanon, New Hampshire, United States
    • University of Southern California
      • Department of Preventive Medicine
      Los Angeles, CA, United States
  • 2002
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2000
    • Baylor College of Medicine
      • Department of Obstetrics and Gynecology
      Houston, TX, United States
  • 1991–1995
    • University of Pittsburgh
      • Department of Environmental and Occupational Health
      Pittsburgh, PA, United States
  • 1993
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 1989–1993
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, WA, United States
  • 1989–1990
    • Kaiser Permanente
      • Center for Health Research (Oregon, Hawaii, and Georgia)
      Oakland, CA, United States