Search

Links between low socioeconomic position and poor health are well established. Most previous research, however, has focused on middle-aged males and has relied on limited socioeconomic data, usually measured at one point over the life course. This paper examines all-cause, cardiovascular, and noncardiovascular mortality in women in relation to socioeconomic position at different stages of the life course. Information was collected in 1965, 1974, 1983, and 1994 and included recalled father's occupation and education as a measure of childhood socioeconomic position and the respondent's household income, education and occupation, and spouse's occupation from a sample of 3,087 women participating in the Alameda County Study. Cox regression models were used to estimate hazard ratios for risk of death. Lower childhood socioeconomic position was associated with an increased mortality due to cardiovascular disease (hazard ratio (HR) = 1.29, 95% confidence interval (CI): 1.09, 1.54) but was unrelated to death due to other causes (HR = 0.97, 95% CI: 0.82, 1.15). Overall mortality was higher among women reporting the lowest level of education (HR = 1.17, 95% CI: 0.99, 1.39), but education was most strongly related to noncardiovascular disease-related deaths (HR = 1.41, 95% CI: 1.10, 1.81). Low household income was also associated with higher mortality, for both cardiovascular disease-related (HR = 1.47, 95% CI: 1.14, 1.91) and noncardiovascular disease-related (HR = 1.30, 95% CI: 1.03, 1.63) deaths. Both early and later life indicators of socioeconomic position contribute to increased mortality risk among socioeconomically disadvantaged women, but these effects appear stronger for cardiovascular mortality.

Objective To estimate the prevalence, incidence, survival, and disease characteristics of systemic sclerosis (SSc) in the Detroit tricounty area. Methods A census of SSc cases for the period 1989–1991 was conducted in the Detroit area, using multiple sources for case identification. Diagnoses were verified by medical record review. Capture-recapture analysis was used to estimate the total SSc population. Cases of localized scleroderma (morphea and linear disease) were excluded. Results Based on 706 verified cases of SSc, prevalence was initially estimated to be 242.0 cases per million adults (95% confidence interval [95% CI] 213–274), with an annual incidence of 19.3 new cases per million adults per year (95% CI 12.4–30.2). Capture-recapture analysis, based on the degree of overlap of verified cases among multiple sources, resulted in a revised prevalence estimate of 276 cases per million adults (95% CI 245–310). Sex- and race-specific prevalence estimates were significantly higher for women than for men, and for blacks than for whites. The average age at diagnosis was significantly younger for blacks than for whites. Compared with white patients, black patients were almost twice as likely to have diffuse disease (prevalence proportion ratio 1.86, 95% CI 1.48–2.35). Median survival was ∼11 years. Factors negatively affecting survival included male sex (hazard ratio 1.81, 95% CI 1.29–2.55) and older age at diagnosis (hazard ratio 1.04, 95% CI 1.03–1.05). Conclusion This study establishes baseline estimates of SSc occurrence and characteristics in a large US cohort consisting primarily of black adults and white adults. These data should facilitate research regarding the role of geographic, ethnic, racial, and environmental factors for this disease in comparison populations.

1515 Background: Renal cell carcinoma (RCC) is the 8thleading cancer in women, commonly diagnosed at more advanced stage. Oxidative stress has been considered to play an important role in the pathogenesis of RCC. Various dietary micronutrients have antioxidant properties, including carotenoids, vitamin C, and vitamin E, and thus diets rich in these nutrients have been evaluated in relation to renal cancer prevention. The aim of this study is to explore the relationship between antioxidant micronutrient and RCC risk in the Women’s Health Initiative (WHI). Methods: A total of 91,913 postmenopausal women enrolled between 1993 and 1998 and followed through July 2013 were included in the analysis. Dietary micronutrient intake was estimated from the baseline WHI food frequency questionnaire, and data on supplement use was collected via interview-based inventory procedure. RCC cases were ascertained from medical records and centrally adjudicated. Risk for RCC associated with α-carotene, β-carotene, β-cryptoxanth...

1558 Background: A rare non-conservative substitution (G84E) in the highly conserved MEIS-interacting domain of the homeobox transcription factor gene HOXB13 has been shown to be associated with an...

5034 Background: Prostate cancer has an excellent prognosis with a 10-year relative survival of 99.7%. The long survival for this common cancer raises questions about the risk of second primary mal...

163 Background: Androgen deprivation therapy (ADT) is the cornerstone treatment of metastatic prostate cancer (PC), but is frequently used in the non-metastatic (M0) setting. After a variable period of hormone sensitivity, most patients develop castration-resistant prostate cancer (CRPC). These men are at increased risk of developing bone metastases (BM), particularly in those with higher serum PSA and shorter PSA doubling time (DT). The epidemiology and natural history of M0 CRPC has not been well studied in a population-based setting. Methods: Using HFHS patient records, a retrospective cohort study was conducted among 723 men diagnosed with M0 PC between 1996 and 2005 (with follow-up [f/u] for outcomes through 12/31/2008), who received ADT, including 613 men with serial PSA measurements for CRPC determination. CRPC was defined as 2 consecutive PSA rises, with “high-risk” defined as PSA ≥ 8 ng/mL or PSA DT ≤ 10 months (mos) after the development of CRPC. The risk of subsequent BM was estimated for the overall cohort and for the CRPC and non-CRPC subsets. Results: The median age among patients in the study was 73 years, 48% were African American, and median f/u time after ADT initiation was 58 mos. 15% (n=93) met criteria for CRPC during f/u (with a median of 23 mos between ADT initiation and establishment of CRPC), with the majority considered being at high risk (n=81). Among the entire cohort, 74 men (10%) developed BM during f/u. The rate of BM was 4 times higher among CRPC patients compared to non-CRPC patients (p

Background: Statins are the most widely prescribed and most effective cholesterol-lowering drugs used in the United States. Statins are a logical candidate for cancer chemoprevention in that they have multiple cellular effects other than lowering cholesterol, including: inhibition of rho GTPases, induction of apoptosis, and decreasing markers of chronic inflammation. A chemopreventive effect of statins on breast cancer has been suggested, however there is significant variation in inter-individual response to statins, and underlying genetic differences may modify the effect of statins on cancer risk. The purpose of this analysis was to evaluate whether there is an interaction between genes modifying statin metabolism and statin use in relationship with breast cancer risk in a case-control study nested within the Women's Health Initiative (WHI) Observational Study (OS). Methods: Genome Wide Association Study (GWAS) data on 30,380 SNPS were available for 1,683 breast cancer cases and 1,683 one-to-one matched controls from the WHI and were included in Cancer Genetic Markers of Susceptibility (CGEMS). Matching criteria were: age at screening, enrollment date, race/ethnicity (all were White), hysterectomy status at baseline and history of breast cancer at baseline. Statin use, sociodemographic information and potentially confounding variables were evaluated at baseline and breast cancer diagnoses were centrally adjudicated. We examined interactions between baseline statin use (yes or no) and 22 SNPs in or near 9 candidate lipid metabolism genes using a conditional logistic model adjusted for features at baseline associated with case/control status. We also examined interactions between statin use and all available SNPs from the GWAS after adjustment for significant features. Results: There were two SNPs out of the 22 SNPs in or near the lipid genes of interest that were nominally significant; rs1529711 in the CARM1 gene [near candidate gene SMARC4, minor allele frequency (MAF) 15%], Pint=0.04, and rs9282564 in the ABCB1 gene (MAF 10%), Pint=0.01. When all GWAS SNPs were examined for interactions with statin use, 34 SNPs achieved statistical significance using a 5% false discovery rate. The GWAS SNP with the greatest evidence for interaction with statin use on breast cancer risk was rs2875218 (Pint=0.0000076). Conclusion: Two SNPs (rs1529711 and rs9282564) near candidate genes (SMARC4 and ABCB1, respectively) showed trends as effect modifiers of statins on breast cancer risk. SMARC4 is a SWI/SNF related, matrix associated, actin dependent regulator of chromatin, and was identified as a candidate effect modifier in a genome-wide study of statin induced myopathy (Link et al., NEJM, 2008). ABCB1 encodes a large transmembrane protein integral to the blood-brain barrier and functions as a drug-transport pump between brain and blood which attenuated LDL-C reduction in a study by Newman and Hulley (JAMA 1996). From the genome-wide analyses, a SNP (rs2875218) located between PRDX3P3 and FREM2 on chromosome 13 was strongly implicated as interacting with statin use on breast cancer risk. Future analyses will examine tagSNPs covering genomic regions of interest including candidate genes and loci identified through this genome-wide examination of SNP x Statin interactions. We will also explore the associations by statin subtype (lipophilic, hydrophilic). Genetic associations such as these, if confirmed, may have implications in terms of personalized medicine, given that statin efficacy in relation to breast cancer risk may be increased or decreased in individuals dependent on inherited genetic polymorphisms. Citation Format: Allison M. Jay, Cathryn H. Bock, Gregory Dyson, Jennifer L. Beebe-Dimmer, Lifang Hou, Barbara V. Howard, Ross Prentice, Michael S. Simon. The effect of genetic variants on the relationship between statins and breast cancer in the Women's Health Initiative Observational Study. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 07.

e15147 Background: Androgen deprivation therapy (ADT) is the cornerstone treatment of advanced PC, but is frequently used in the M0 setting. After a variable period of hormone-sensitivity, most patients develop CR disease (rising prostate-specific antigen [PSA] despite ongoing ADT). These men are at increased risk of developing bone metastases (BMT), particularly in those with higher serum PSA and shorter PSA doubling time (DT). The epidemiology and natural history of M0 CRPC has not been well-studied in a population-based setting. Methods: A retrospective cohort study was conducted using HFHS administrative data and included 691 men diagnosed with M0 PC between 1996 and 2005, who received ADT, with serial PSA measurements to determine CR. Patient records through 12/31/2008 were reviewed for outcomes of interest. CRPC was defined as 2 consecutive PSA rises, with “high risk” defined as PSA ≥8 ng/mL or PSA DT ≤10 months (mos) after the development of CRPC (Smith MR et al. Lancet 379:39-46, 2012). The risk of BMT was estimated for the entire cohort and for the CRPC and high-risk CRPC subsets. Results: Of the 691 patients included in the cohort (median age: 73 years, 48% African American), 98% received only GnRH agonists and 2% had orchiectomy. Median follow-up for the entire cohort after ADT initiation was 49 mos (IQR=45). 101 patients (15%) met criteria for CRPC during follow-up, with a median of 18 mos on active ADT prior to CRPC development (IQR=14). Of CRPC patients, 85% met criteria for high-risk (of those, 16% had PSA ≥8 ng/mL, 12% had PSA DT ≤10 mos, and 72% had both). Among all patients, 12% (n=82) developed BMT during follow-up, with 42% (n=36) of the high-risk CRPC subset developing BMT. Median time from high-risk CRPC to BMT was 9 mos (IQR=17). Conclusions: The HFHS resource allowed for our investigation of PSA characteristics corresponding to disease progression in a racially diverse patient population. A substantial proportion of M0 PC patients on ADT will eventually develop CR disease. Once a patient has CRPC, the risk of BMT is relatively high.

BACKGROUND: Renal cell carcinoma (RCC) is made up of several histological subtypes, the most common of which include clear cell, papillary and chromophobe RCC. These subtypes possess distinct genetic and clinical characteristics, and may also differ in etiology. To better understand whether the associations with established RCC risk factors [body mass index (BMI), smoking, hypertension, family history of kidney cancer] differ across subtypes, we conducted analyses in two large case-control studies conducted in the U.S. (1,217 cases, 1,235 controls) and Central and Eastern Europe (1,097 cases, 1,476 controls). METHODS: Histology was ascertained for 706 U.S. cases (58% of participating cases) and 891 European cases (81%) through a central pathology review conducted by a single pathologist. For cases not included in the central review, histology was abstracted from the original diagnostic pathology report. Case-only analyses were performed to compute odds ratios (OR) and 95% confidence intervals (CI) summarizing subtype differences by age, sex, and race. Case-control analyses were performed to compute subtype-specific ORs for other risk factors using polytomous regression. RESULTS: In case-only analyses, papillary cases (N=237) were older (OR=1.2, 95% CI=1.1-1.4 per 10-year increase), less likely to be female (OR=0.5, 95 % CI=0.4-0.8) and more likely to be black (OR=2.6, 95% CI=1.8-3.9) compared to clear cell cases (N=1,524). In case-control analyses, BMI was associated with clear cell (OR=1.5, 95% CI=1.3-1.7 per 10 kg/m2 increase) and chromophobe RCC (N=80; OR=1.5, 95% CI=1.1-2.0), but not papillary RCC (OR=1.1, 95% CI 0.9-1.5; heterogeneity test vs. clear cell, P=0.006). No differences across subtypes were observed for other risk factors. Analyses stratified by study and restricted to cases included in the central pathology review yielded virtually identical findings. CONCLUSIONS: Our results from this analysis, to our knowledge the most comprehensive investigation of etiologic heterogeneity across RCC histologic subtypes conducted to date, support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity-RCC association differs by histology. These findings underscore the importance of accounting for histologic subtype in investigations of RCC etiology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5515. doi:1538-7445.AM2012-5515

DNA methylation is an indicator of the initiation of prostate carcinogenesis and as such has utility as a marker of risk in pathologically negative prostate tissue samples. We conducted a matched case-control study nested in a historical cohort of over 6,000 men with pathologically benign prostate specimens identified between January 1991 and November 2002 with no previous history of prostate cancer. Eligible cases were diagnosed with prostate cancer at least one year after cohort entry. Controls were selected through incidence density sampling and matched to cases on date and age at cohort entry, race, and type of specimen. In 310 matched prostate cancer case-control pairs (65% white; 35% African American), we assayed the DNA of the benign prostate specimen for presence of methylation in a five-gene panel (APC, RARB, CCND2, RASSF1, MGMT) and then estimated the risk of developing prostate cancer associated with methylation at each gene for the whole sample and stratified by race. Overall, methylation of RARB had the strongest association with prostate cancer risk (HR = 1.94; 95% CI = 1.30 – 2.91). In race-stratified analyses, the majority of the increased risk associated with RARB was found in the African-American sample (HR = 3.40; 95% CI = 1.68–6.88). In addition, APC was also associated with increased risk for prostate cancer in the African-American sample (HR = 2.17; 95% CI = 1.09–4.29). In a model that included both genes, only RARB remained statistically significantly associated with prostate cancer (HR = 3.14; 95% CI = 1.54–6.44). In whites, methylation was not associated with prostate cancer for any of the five genes assayed. In summary, positive methylation status at RARB and APC in pathologically benign prostate is associated with significant increased risk for subsequent prostate cancer, but primarily in African-American men. Whether this race-specific risk is due to racial differences in environmental stimuli and/or biology is unclear, but further study of DNA methylation in the earliest stages of prostate carcinogenesis may help explain the disproportionate burden of this disease among African-American men. This abstract is one of the 14 highest scoring abstracts of those submitted for presentation at the 35th Annual Meeting of the American Society of Preventive Oncology, held March 5–8, 2011 in Las Vegas, NV.

4559 Background: ADT is standard treatment for late-stage PC and is increasingly being used in the locally advanced setting. Fractures are a well-recognized side effect of ADT, but less is known re...

Evidence of the existence of major prostate cancer (PC)-susceptibility genes has been provided by multiple segregation analyses. Although genomewide screens have been performed in over a dozen independent studies, few chromosomal regions have been consistently identified as regions of interest. One of the major difficulties is genetic heterogeneity, possibly due to multiple, incompletely penetrant PC-susceptibility genes. In this study, we explored two approaches to overcome this difficulty, in an analysis of a large number of families with PC in the International Consortium for Prostate Cancer Genetics (ICPCG). One approach was to combine linkage data from a total of 1,233 families to increase the statistical power for detecting linkage. Using parametric (dominant and recessive) and nonparametric analyses, we identified five regions with "suggestive" linkage (LOD score >1.86): 5q12, 8p21, 15q11, 17q21, and 22q12. The second approach was to focus on subsets of families that are more likely to segregate highly penetrant mutations, including families with large numbers of affected individuals or early age at diagnosis. Stronger evidence of linkage in several regions was identified, including a "significant" linkage at 22q12, with a LOD score of 3.57, and five suggestive linkages (1q25, 8q13, 13q14, 16p13, and 17q21) in 269 families with at least five affected members. In addition, four additional suggestive linkages (3p24, 5q35, 11q22, and Xq12) were found in 606 families with mean age at diagnosis of < or = 65 years. Although it is difficult to determine the true statistical significance of these findings, a conservative interpretation of these results would be that if major PC-susceptibility genes do exist, they are most likely located in the regions generating suggestive or significant linkage signals in this large study.

Background Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. Methods Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate ( Results While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). Conclusions Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.