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Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population. Participants were randomly selected among individuals residing in the Houston area who are enrolled in the Mexican-American Cohort study. Using a custom Illumina GoldenGate Panel, we genotyped DNA from 4,662 cohort participants for 87 Ancestry-Informative Markers. On average, the participants were of 50.2% Native American ancestry, 42.7% European ancestry and 7.1% African ancestry. Using multivariate linear regression, we found BMI and Native American ancestry were inversely correlated; individuals with 80% Native American ancestry. Furthermore, we demonstrated an interaction between BMI and Native American ancestry in diabetes risk among women; Native American ancestry was a strong risk factor for diabetes only among overweight and obese women (OR = 1.190 for each 10% increase in Native American ancestry). This study offers new insight into the complex relationship between obesity, genetic ancestry, and their respective effects on diabetes risk. Findings from this study may improve the diabetes risk prediction among Mexican-American individuals thereby facilitating targeted prevention strategies.

Patients with chronic lymphocytic leukemia (CLL) are known to have an increased incidence of second cancers, but the contribution of commonly used frontline therapies to the incidence of second cancers is unclear. We report on the characteristics, incidence, outcomes and factors associated with second cancers in 234 patients receiving fludarabine, cyclophosphamide and rituximab (FCR) based regimens in the frontline setting. The risk of second cancers was 2.38 times higher than the expected risk in the general population. Ninety-three patients (40%) had other cancers before and 66 patients (28%) after FCR. Rates of therapy related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) (5.1%) and Richter transformation (RT) (9%) were high, while solid tumors were not increased. Overall survival of patients with second cancers after frontline FCR was shorter (median of 4.5 years) compared to patients with and without prior cancers. Second cancer risk after frontline FCR is mainly due to high rates of t-AML/MDS and RT, and as speculated the survival of affected patients is shorter.

Background Epidemiological studies have found that particulate matter is associated with increases in blood pressure. Yet, less is known about the effects of specific sources or constituents of particulate matter, such as diesel particulate matter or polycyclic aromatic hydrocarbons (PAHs). We evaluated associations between self-reported hypertension and residential air levels of diesel particulate matter and PAHs among individuals of Mexican origin living in a large inner city. Methods The Mano a Mano cohort (established in 2001 by the University of Texas MD Anderson Cancer Center) is comprised of individuals of Mexican origin residing in Houston, Texas. Using geographical information systems, we linked modeled annual estimates of PAHs and diesel particulate matter at the census tract level from the 2002 and 2005 U.S. Environmental Protection Agency’s National-Scale Air Toxics Assessment to baseline residential addresses of cohort members who enrolled from 2001 to 2003 or 2004 to 2006, respectively. For each enrollment period, we applied mixed-effects logistic regression models to determine associations between diesel particulate matter and PAHs, separately, and self-reported hypertension while adjusting for confounders and the clustering of observations within census tracts and households. Results The study population consisted of 11218 participants of which 77 % were women. The mean participant age at baseline was 41 years. Following adjustment for age, there was a dose-dependent, positive association between PAHs and hypertension (medium exposure, adjusted odds ratio (OR) = 1.09, 95 % CI: 0.88-1.36; high exposure, OR = 1.40, 95 % CI: 1.01-1.94) for individuals enrolled during 2001–2003; associations were generally similar in magnitude, but less precise, following adjustment for age, gender, smoking, and BMI. No association was detected for the later period. There was no evidence of an association between residential levels of diesel particulate matter and hypertension. Conclusions This study builds on a limited number of prior investigations of the association between ambient air levels of PAHs or diesel particulate matter and hypertension by focusing on a relatively young cohort of predominantly adult women of Mexican origin. Future analyses are warranted to explore associations in the cohort using incident hypertension when sufficient data become available and to further examine associations between specific chemical constituents of particulate matter and hypertension in this and other populations.

Sunlight causes DNA damage, including bulky lesions that are removed effectively by the nucleotide-excision repair (NER) pathway. There are at least eight core NER proteins participating in the pathway, and genetic variations in their genes may alter NER functions. We hypothesized that some NER variants are associated with risk of cutaneous melanoma. In a hospital-based case-control study of 602 non-Hispanic White patients with cutaneous melanoma and 603 age- and sex-matched cancer-free controls, we genotyped five common non-synonymous single-nucleotide polymorphisms identified to date and assessed their associations with risk of cutaneous melanoma. We found that a significantly increased risk of cutaneous melanoma was associated with XPD 751Lys/Gln [adjusted odds ratio (OR), 1.55 and 95% confidence interval (95% CI), 1.12-2.16] and XPD 751Gln/Gln (OR, 1.66; 95% CI, 1.03-2.68) genotypes compared with the XPD 751Lys/Lys genotype as well as XPD312Asp/Asn (OR, 1.54; 95% CI, 1.11-2.12) and XPD312Asn/Asn (OR, 1.75; 95% CI, 1.05-2.90) genotypes compared with the XPD 312Asp/Asp genotype. This increased risk was not observed in the other three XPC and XPG single-nucleotide polymorphisms. Moreover, the number of the observed XPD at-risk genotypes (i.e., 312Asn/Asn+Asn/Asp and 751Gln/Gln+Lys/Gln) was associated with cutaneous melanoma risk in a dose-response manner (OR, 1.47; 95% CI, 0.97-2.23 for one at-risk genotype; OR, 1.83; 95% CI, 1.29-2.61 for two at-risk genotypes; Ptrend < 0.001). However, we found no evidence of any interaction between XPD genotypes with XPC and XPG genotypes or the known risk factors. We concluded that genetic variants of the XPD gene might serve as biomarkers for susceptibility to cutaneous melanoma. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2526–32)

Sunlight causes various kinds of DNA damage, including oxidative lesions that are removed effectively by the base excision repair (BER) pathway, in which ADPRT, XRCC1 and APE1 play a key role. However, genetic variation in these genes may alter their functions. We hypothesized that ADPRT, XRCC1 and APE1 polymorphisms are associated with risk of cutaneous melanoma (CM). In a hospital-based case‐control study of 602 CM patients and 603 cancer-free control subjects frequency matched on age, sex and ethnicity, we genotyped for three non-synonymous single nucleotide polymorphisms (SNPs) (i.e. the ADPRT Val762Ala, XRCC1 Arg399Gln and APE1Asp148Glu) and assessed their associations with risk of CM. We found no significant difference in the allele frequencies between cases and controls for any of these three SNPs. However, we found that, compared with the APE1 Asp/Asp genotype, a significantly decreased risk of CM was associated with the APE1 Asp/ Glu [adjusted odds ratio (OR), 0.60; 95% confidence interval (CI), 0.41‐0.86], Glu/Glu (OR, 0.58; 95% CI, 0.38‐0.88) and combined APE1 Asp/Glu+Glu/Glu (OR, 0.59; 95% CI, 0.42‐0.83) genotypes, but not for other XRCC1 variant genotypes. Moreover, there was evidence for a possible gene‐gene interaction between XRCC1 and APE1 variants in the association with risk of CM (P ¼ 0.030). We conclude that the APE1 Glu variant may have an effect or interact with XRCC1 in the etiology of CM or in linkage disequilibrium with other untyped protective alleles. Larger studies with more SNPs in the BER genes are needed to verify these findings.

The FAS/FAS ligand (FASLG) system has a key role in regulating cell growth and thus tumorigenesis. Functional promoter polymorphisms of the FAS and FASLG genes alter the transcriptional activities, but no published study has investigated the role of these polymorphisms in the etiology of cutaneous malignant melanoma (CMM). In a hospital-based, case-control study of 602 non-Hispanic white CMM patients and 603 cancer-free age- and sex-matched control subjects, we genotyped FAS-1377G>A, FAS-670A > G, FASLG-844T> C and FASLG-IVS2nt-124G>A polymorphisms and assessed their respective associations with CMM risk. We found that an increased risk of CMM was associated with the FAS-1377GG [adjusted odds ratio (OR) =1.32; 95% confidence interval (CI) =1.00-1.75 for -1377GG] and -670AA (adjusted OR =1.28; 95% CI=1.00-1.65 for - 670AA) genotypes compared to the -1377AA/AG and - 670AG/GG genotypes, respectively; an increased risk of CMM was associated with the FASLG-IVS2nt-124AG+GG (OR =1.54; 95% CI=1.18-2.01) genotype compared to the AA genotype, but no evident risk was associated with any of the FAS-844T> C genotypes. In the combined analysis of these four variant alleles, we found that, compared to those having 0-3 variants, those having 4-8 variant alleles had a significantly increased risk for CMM (OR =1.38; 95% CI=1.10-1.73), and this risk was more pronounced in subgroups of old (>50 years) males, and those who were at low risk of sunlight-induced CMM, except for having fair skin colour, moles, dysplastic nevi and a family history of cancer. In conclusion, genetic variants in the FAS and FASLG genes may contribute to the etiology of CMM in the general population, particularly in those with a low risk of sunlight-induced CMM.

Self-rated health (SRH), a consistent predictor of mortality among diverse populations, is sensitive to health indicators and social factors. American-born Hispanics report better SRH than their foreign-born counterparts but simultaneously report poorer health indicators and have shorter life expectancy. Using a matched prospective cross-sectional design, we analyzed data from 631 age-matched pairs of women, born in the United States or Mexico, enrolled in a cohort study based in Houston, Texas. Our first goal was to describe the relationships between SRH and health behaviors, physician-diagnosed chronic conditions, acculturation, and socioeconomic status (SES) by birthplace. Our second goal was to investigate the relative influence of SES, acculturation, health behaviors, and physician-diagnosed conditions in explaining expected differences in SRH between the two groups. Number of chronic conditions reported, particularly depression, more strongly influenced SRH than SES, acculturation, or reported health risk behaviors and the influence of birthplace is accounted for by these factors.

BACKGROUND. Several reports have shown that obesity is associated with increased risk of biochemical failure after radical prostatectomy. However, limited information is available regarding the impact of obesity on prostate cancer progression after radiotherapy. The current study sought to determine whether obesity was an independent predictor of biochemical failure (BF) and clinical recurrence (CF) among patients treated with external-beam radiotherapy (EBRT). METHODS. A retrospective analysis was performed on 873 patients receiving EBRT as the sole treatment for localized prostate cancer between 1988 and 2001. The Kaplan–Meier method, log-rank test, and Cox proportional hazards analyses were performed. RESULTS. Of the 873 patients, 18% were mildly obese and 5% were moderately to severely obese. Obesity was related to younger age at diagnosis (P < .001), more recent year of diagnosis (P = .03), and race (P = .03), with African-American men having the highest obesity rates. During a mean follow-up of 96 months, 295 patients experienced BF and 127 had CF. On multivariate analysis, controlling for clinical and treatment characteristics, increased body mass index (BMI) significantly predicted BF (hazards ratio [HR] = 1.04; 95% confidence interval [95% CI], 1.02–1.07) with a positive trend by BMI category (P = .001). Similar results were found when the outcome was CF; BMI remained an independent predictor of progression (HR = 1.05; 95% CI, 1.01–1.09), with a statistically significant trend by increased BMI category (P = .03). CONCLUSIONS. The current findings validate the important role of obesity, not only on BF but also on CF, and suggest a link to the biologic basis of tumor progression that can be therapeutically exploited. Cancer 2006. © 2006 American Cancer Society.

BACKGROUND: Mutagen sensitivity, measured as mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro, has been used to study susceptibility to various epithelial cancers. Patients with xeroderma pigmentosum are highly sensitive to ultraviolet (UV) light due to inherited defects in DNA repair and have a 1000-fold higher risk of UV-induced skin cancer than the general population. However, an association between UV-induced chromosomal aberrations and risk of skin cancer in the general population has not been established. METHODS: We assessed in vitro UVB-induced chromatid breaks in a hospital-based case-control study. The study included 469 patients with skin cancer (231 with nonmelanoma skin cancer [NMSC] and 238 with cutaneous malignant melanoma [CMM]) and 329 cancer-free control subjects. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Compared with the frequency of UVB-induced chromatid breaks per cell in control subjects (mean = 0.28 breaks per cell, 95% CI = 0.27 to 0.30), that in NMSC patients (basal cell carcinoma [BCC], n = 143, mean = 0.36 breaks per cell, 95% CI = 0.33 to 0.39 and squamous cell carcinoma [SCC], n = 88, mean = 0.35 breaks per cell, 95% CI = 0.32 to 0.38) was higher (P = .001 and P < .001, respectively), but that in CMM case patients (mean = 0.30 breaks per cell, 95% CI = 0.28 to 0.33) was not (P = .22). A frequency of chromatid breaks per cell above the median of control subjects was associated with nearly threefold increased risks for BCC (OR = 2.78, 95% CI = 1.79 to 4.30) and SCC (OR = 2.62, 95% CI = 1.50 to 4.60), but not with an increased risk of CMM. A dose-response relationship was evident between mutagen sensitivity and risk for both BCC (Ptrend < .001) and SCC (Ptrend < .001). Multiplicative interactions between mutagen sensitivity and sun exposure variables on risk, particularly for sunburn in BCC and hair color, tanning ability, and family history of skin cancer in SCC, were seen for NMSC but not CMM. CONCLUSIONS: UVB-induced mutagen sensitivity may play a role in susceptibility to NMSC but not to CMM.

Little is known about the etiology of myelodysplastic syndromes (MDS). A hospital-based case-control study of 354 adult de novo MDS cases and 452 controls was conducted to investigate associations between lifestyle characteristics and MDS risk. The distribution by French-American-British (FAB) type was 67 (19%) refractory anemia (RA), 38 (11%) refractory anemia with ringed sideroblasts (RARS), 43 (12%) chronic myelomonocytic leukemia (CMML), 136 (38%) RA with excess blasts (RAEB), and 70 (20%) RAEB in transformation (RAEBT). Multivariate logistic regression analyses were performed among all MDS cases and among each FAB type and gender. For all MDS combined, family history of hematopoietic cancer (odds ratio (OR) = 1.92), smoking (OR = 1.65), and exposure to agricultural chemicals (OR = 4.55) or solvents (OR = 2.05) were associated with MDS risk. Among RA/RARS cases, smoking (OR = 2.23) and agricultural chemical exposure (OR = 5.68) were the only risk factors identified. For RAEB/RAEBT cases, family history of hematopoietic cancer (OR = 2.10), smoking (OR = 1.52), and exposure to agricultural chemicals (OR = 3.79) or solvents (OR = 2.71) were independent risk factors. Drinking wine reduced risk for all FAB types by almost 50% (OR = 0.54). We found a joint effect between smoking and chemical exposure with the highest risk among smokers exposed to solvents/agricultural chemicals (OR = 3.22). Results from this large study suggest that several factors play a role in MDS predisposition with possible joint effects. Risk profiles seem to differ by FAB type and gender.

Background Little is known about the role of inherited genotypes in prostate cancer (PC) progression. This prospective study evaluated the predictive value of androgen receptor (AR) polymorphisms (CAG and GGC repeats) among prostatectomy patients. Methods We studied 354 patients registered at M. D. Anderson Cancer Center from 1991 to 2001. Kaplan–Meier and Cox proportional hazard analyses were used. Results During an average follow-up of 56 months, 66 (19%) post-prostatectomy patients experienced biochemical failure (BF). Patients with higher CAG repeats (CAG ≥ 24) had significantly longer BF-free survival (BFFS) than those with fewer repeats (CAG ≤ 23) (P = 0.04). Higher CAG repeats were significantly associated with lower BF risk among Whites and African Americans. Among Whites, longer CAG repeats (relative risk (RR) = 0.45, P = 0.03) and Gleason score ≥8 (RR = 19.33, P = 0.005) remained significant BFFS predictors in multivariate analysis. GGC repeats were not associated with BF. Conclusions Our data showed that an inherited polymorphism (CAG repeats) in the AR is related to differences in genetic susceptibility to BF, supporting the hypothesis that increased AR activity may play a role in PC progression. © 2004 Wiley-Liss, Inc.

Purpose To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT). Patients and Methods From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with postorchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males. Results After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P < .01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P < .01). An increased mortality was evident in patients treated with and without mediastinal XRT. Conclusion Long-term survivors of seminoma treated with postorchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.

Oxidative damage is an important factor in prostate carcinogenesis, and overexpression of human MutT homolog (hMTH), a repair gene that removes oxidative damage, is a molecular marker of cellular oxidative stress. Therefore, we tested the hypothesis that overexpression of hMTH in unaffected (normal) surrogate tissue is associated with risk of prostate cancer in a pilot study of 51 patients with diagnosed prostate cancer and 50 age- and ethnicity-matched controls. Total RNA was extracted from phytohemagglutinin-stimulated peripheral blood lymphocytes of these subjects. We performed the real-time reverse transcription–polymerase chain reaction assay to evaluate the relative mRNA expression of three oxidative-damage-repair genes, human MutM homolog (hMMH), hMTH, and human MutY homolog (hMYH), with β-actin and human O6-methylguanine DNA methyltransferase (hMGMT) as the internal controls. The relative gene expression levels of hMMH and hMTH were borderline higher in the cases than in controls (15.3% and 28.8% higher, respectively; P = 0.046 and P = 0.035, respectively), whereas no increase was observed for hMYH and hMGMT. With the median of the controls' values as the cutoff point, we observed that a high expression level of hMTH, but not of other genes, was associated with a significantly increased risk of prostate cancer (odds ratio = 2.62; 95% confidence interval = 1.13–6.75) after adjustment for age and ethnicity. These results suggested that increased expression of hMTH in peripheral lymphocytes may be a risk factor for prostate cancer and support our priori hypothesis. Although our findings were biologically plausible and consistent with the literature, they were preliminary and need to be confirmed in larger studies. In addition, a correlation between the expression level of hMTH and the level of oxidative DNA damage in the target tissues needs to be established as well. © 2003 Wiley-Liss, Inc.

Hispanic Americans comprise the largest and fastest-growing ethnic minority in the USA. In Houston, Texas, 44% of the population is of Hispanic descent, with the majority being Mexican Americans (78%). This population is under-represented in health-related research despite their high prevalence of obesity and diabetes, which may predispose them to cancer and other chronic conditions. Recognizing the need for a greater research effort into the health risks of Hispanic Americans, the population-based Mexican American (Mano a Mano) Cohort study was launched in 2001. This is an open cohort with enrolment ongoing to 2019, and as of 30 June 2014, 23 606 adult participants from over 16 600 households were enrolled. Bilingual interviewers elicit information in person on demographics, acculturation, lifestyle, occupation, medical history, family cancer history, self-reported and measured height and weight, and other exposures. Urine, blood and saliva samples have been collected at baseline from 43%, 56% and 63% of participants, respectively. DNA samples are available for about 90% of participants. Incident cancers and other chronic diseases are ascertained through annual telephone re-contact and linkage to the Texas Cancer Registry and/or medical records. Molecular data such as genetic ancestry markers, blood telomere length and HbA1c, a marker of impaired glucose tolerance, are available for a substantial proportion of the participants. Data access is provided on request [manoamano@mdanderson.org]. For further information please visit [www.mano-mano.us].

Purpose: To examine the frequency of additional neoplasms preceding and following the diagnosis of mantle cell lymphoma (MCL). Patients and methods: A total of 156 patients with MCL treated on the hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternated with methotrexate and cytosine arabinoside (Hyper-CVAD/M-A) program with or without rituximab from 1994 to 2000 were the subjects of this report. Results: These patients were followed for a median time of 26 months, and a total of 32 (21 %) additional neoplasms were diagnosed, 21 preceding the diagnosis of MCL and 1 I following MCL. After excluding certain types of non-invasive neoplasms, including basal cell carcinoma, meningioma and cervical intraepithelial neoplasia, we observed seven second malignancies after the diagnosis of MCL, and the 5-year cumulative incidence rate of second malignancy was 11%. The observed-to-expected (O/E) ratio was 7/0.07 = 100 [95% confidence interval (CI) 49.3 to 186.6; P

Recent studies estimate that individuals of African or Latin American ancestry represent less than 4% of samples analyzed to date in genome-wide association studies. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts in these populations. Here, we performed a genome-wide association study (GWAS) meta-analysis of prostate cancer in Latino men to search for risk loci that may be important in this population. We combined GWAS data for 1034 cases and 1046 controls genotyped with the Illumina 660 Beadarray with GWAS data for 1235 cases and 1053 controls genotyped with the Illumina Oncoarray as part of the ELLIPSE U19 GAME-ON Consortium. A total of ~11 million genotyped and imputed SNPs of ≥1% frequency were tested for association with prostate cancer risk in logistic regression models controlling for age, study and genetic ancestry. Genome-wide significant associations were observed with 24 variants all located at 8q24 (128.484-128.548), and which capture the first reported prostate cancer susceptibility locus in ‘region 1’ of 8q24. The most significant association genome-wide was with SNP rs7824776 (risk allele frequency, 0.35; OR=1.69, p=3.4x10-11). No novel genome-wide significant associations were noted outside of 8q24. We observed a high degree of generalizability of known prostate cancer risk loci, with 78 (76%) of the 103 known risk variants having effects that were directionally consistent in their association with prostate cancer risk as previously reported, of which 31 (30%) were statistically significant with p < 0.05. In addition to these findings from the largest GWAS of prostate cancer in Latinos conducted to date, we will also present the results investigating effect heterogeneity by local ancestry (i.e. proportion Native American vs. European). In addition, we will present a comparison of polygenic risk models between Latinos, African Africans and men of European ancestry that incorporate the known risk loci to better understand how genetic risk tracks with population differences in prostate cancer incidence. Citation Format: Hannah Hopp, Sue Ingles, Chad Huff, Xin Sheng, Brandi Weaver, Mariana Stern, Sara Strom, Ian Thompson, David Conti, Christopher A. Haiman. A genome-wide association study of prostate cancer in Latinos [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1303. doi:10.1158/1538-7445.AM2017-1303

Background: Biobanking is the collection of human biospecimens (tissues, blood, and body fluids) and their associated clinical and outcome data. Hispanics are less likely to provide biologic specimens for biobanking. The purpose of this study was to investigate the association of acculturation, nativity status, and years living in the United States with participation in biobanking among individuals of Mexican descent. Methods: Participants were 19,212 adults of Mexican descent enrolled in an ongoing population-based cohort in Houston, TX. Participants were offered the opportunity to provide a blood, urine, or saliva sample for biobanking. Acculturation was assessed with the bidimensional acculturation scale for Hispanics and scores were categorized into “low acculturation,” “bicultural,” and “high-acculturation.” Results: After multivariable adjustment, we found an increased likelihood of participation in biobanking among individuals classified as “bicultural” as compared with “highly acculturated” individuals [OR, 1.58; 95% confidence intervals (CI), 1.10–2.26]. The associations of nativity status and years living in the United States with biobanking were not statistically significant. After stratifying by gender, the associations of acculturation, nativity status, and years living in the United States with biobanking were not statistically significant. Conclusion: Although individuals of Mexican descent who were “bicultural” were more likely to participate in biobanking than individuals who were “highly acculturated,” the difference in rates of participation among acculturation categories was small. The high participation rate in biospecimen collection is likely due to extensive community-engaged research efforts. Future studies are warranted to understand individuals' participation in biobanking. Impact: Community-engaged research efforts may increase Hispanics' participation in biobanking. See all articles in this CEBP Focus section, “Community Network Program Centers.” Cancer Epidemiol Biomarkers Prev; 23(3); 402–8. ©2014 AACR.

Background Higher prostate cancer mortality rates among US immigrants from countries with lower rates suggest environmental influences on prostate carcinogenesis (e.g., diet, body composition). Methods In a study identifying determinants of clinically relevant prostate cancer, we compared plasma concentrations of leptin, an adiposity-related hormone, in 48 men with tumors ≤ 0.5 cc measured after radical prostatectomy and 151 men with tumors > 0.5 cc in volume or with histologic evidence of extraprostatic extension but without metastases (“high-volume disease”), matched by age (± 5 years) and year at diagnosis (± 1 year). Results Men with high-volume disease exhibited higher leptin concentrations overall and after stratification by age, testosterone level, height, and body mass index (BMI). Analysis revealed that men with elevated leptin concentrations had an increased risk of diagnosis with high-volume disease (odds ratio (OR) = 2.35, 95% confidence interval (CI) = 1.01–5.44), as did men with high leptin and high testosterone (OR = 9.73, 95% CI = 2.05–46.24) and men ≥5′8″ with high leptin (OR = 3.67, 95% CI = 1.40–9.63). Conclusions Leptin may affect the risk of clinically relevant prostate cancer through testosterone and factors related to stature and obesity. Prostate 46:62–67, 2001. © 2001 Wiley-Liss, Inc.

DNA repair capacity is central in maintaining normal cellular functions. Variants of several DNA repair genes,including the nucleotide excision repair gene XPD, have been described recently. Because we previously reported that patients with squamous cell carcinoma of the head and neck (SCCHN) had lower DNA repair capacity than healthy controls, we hypothesized that inherited polymorphisms of XPD may contribute to genetic susceptibility to SCCHN, a tobacco-related cancer. To test this hypothesis, we conducted a hospital-based case-control study of 189 SCCHN patients and 496 cancer-free controls who were frequency-matched on age, gender and smoking status. All subjects were non-Hispanic whites. Two XPD polymorphisms (C22541A and A35931C) were typed using the restriction enzymes TfiI and PstI, respectively. Multivariate logistic regression analysis was performed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). In the controls, the frequencies of the variant 22541A and 35931C alleles were 44.7% and 33.8%, respectively. The frequency of the 22541A homozygous genotype (22541AA) was lower in cases (15.9%) than in controls (20.4%) but was not associated with risk (adjusted OR = 0.90; 95% CI = 0.52-1. 56) for SCCHN. The frequency of the 35931C homozygous genotype (35931CC) was higher in cases (16.4%) than in controls (11.5%) and associated with a borderline increased risk (adjusted OR = 1.55; 95% CI = 0.96-2.52) for SCCHN. The risk was higher in older subjects (OR = 2.22; 95% CI = 1.03-4.80), current smokers (OR = 1.83; 95% CI = 0.79-4.27) and current drinkers (OR = 2.59; 95% CI = 1.25-5.34) in the stratification analysis. These results suggest a gene-environment interaction, but this did not reach statistical significance. The findings are limited due to the relatively small numbers in the subgroups and need to be verified by further investigations.

In the general population, there is variation in radiosensitivity associated with cancer risk. However, data on the role of epigenetic factors in the variation of radiosensitivity are scarce. Thus we investigated the effects of smoking and age on the radiosensitivity of human lymphocytes by measuring the frequency of chromosome aberrations after in vitro exposure to gamma rays in peripheral lymphocytes from 441 healthy subjects (18-95 years old). We analyzed the frequency of both spontaneous (baseline) and in vitro gamma-ray-induced (1.5 Gy) chromatid breaks in 50 well-spread metaphases per subject. The overall mean frequencies of spontaneous and induced breaks were 0.02 and 0.45 per cell, respectively. The mean frequency of induced breaks was significantly higher in men than in women (P = 0.03) but did not differ by age or ethnicity. Donors who had ever smoked showed a small but significantly increased frequency of induced breaks (mean = 0.47) compared to nonsmokers (mean = 0.41; P = 0.005). Further stratification and multivariate analyses revealed that the smoking effect was more pronounced in men than in women. These findings support a smoking effect on radiosensitivity in a healthy population, particularly in men. Therefore, when evaluating the association between radiosensitivity and susceptibility to smoking-related cancers, the effect of smoking should be taken into account.

While tumor volume and Gleason scores are the best available prognostic indicators for prostate cancer, contemporary predictive methods are unable to identify which men with Gleason scores of 7 have clinically insignificant tumors that will not progress and which men will develop highly aggressive prostate cancer. Our objective was to evaluate potential environmental determinants of significant prostate cancer. Subjects were patients identified from a universitybased hospital and tertiary cancer center who had undergone radical prostatectomy for prostate cancer. Cases were 103 patients whose tumor volumes were

No risk factor other than cryptorchidism has been consistently associated with testicular cancer, and the influence of diet on testicular cancer risk has not been extensively explored. A few studies have found increased testicular cancer risk in men whose diets are high in fat, red meats, and milk or low in fruits and vegetables. We evaluated the relationship of dietary factors and risk of testicular cancer and also examined whether this risk varied by type of testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center (Houston, TX) of 160 testicular cancer cases diagnosed between 1990 and 1996 and 136 friend-matched controls. The results of multivariable logistic regression analysis showed that after adjustment for age, education, income, ethnicity, cryptorchidism, and total daily calories, increasing total fat, saturated fat, and cholesterol consumption were associated with increasing risk of nonseminoma testicular cancer, with odds ratios (ORs) for the highest vs. the lowest quartiles of 6.3, 5.3, and 4.6, respectively. The risk for seminoma testicular cancer marginally increased with increasing intake of total fat and saturated fat, with ORs for the highest vs. lowest quartiles of 1.9 and 2.1, respectively. Higher total fat consumption was nearly significantly related to increased mixed germ cell tumor risk, with an OR for highest vs. lowest quartile of 4.2. This study supports the hypothesis that diet (particularly high fat consumption) increases testicular cancer risk in young men. However, the small sample size and the possibility that these observations may be due to bias indicate that the relationship of diet and testicular cancer risk needs to be further examined within a prospective or incident case-control study.

In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls. Controls reported consuming higher amounts of foods containing genistein, daidzein, and coumestrol and lower amounts of foods containing campesterol and stigmasterol. Multivariate analysis, after adjustment for age, family history of prostate cancer, alcohol consumption, and total calorie intake, showed an inverse association between coumestrol (p = 0.03) and daidzein (p = 0.07) and prostate cancer risk. Genistein, the most studied phytoestrogen, showed a slight protective effect (p = 0.26). However, a positive association was found between campesterol (p = 0.08) and stigmasterol (p = 0.03) and risk of prostate cancer. These results are suggestive of a possible relationship between phytoestrogen intake and prostate cancer risk. Larger comprehensive studies are needed to further refine the role of phytoestrogen intake in prostate cancer risk.

S26 had an alternative diagnosis for their neurologic symptoms identified after tissue biopsy and/or other work-up. On LP, lower glucose levels (median 54 mg/dL, p1⁄40.02), elevated total nucleated cells (TNC)(median 14/mL, p1⁄40.004), absolute lymphocyte count (ALC) (median 12/mL, p1⁄40.02), CLL cells percentage (median 5%, p1⁄40.05) and count (median 1.5/mL, p1⁄40.02) significantly associated with a final diagnosis of CNS involvement CLL/RS. Despite this association, none reliably discriminated as to whether the etiologies of patients’ neurologic symptoms were due to clinically significant CNS involvement by CLL/RS or another etiology. Conclusions: Neurological symptoms requiring an LP are rare in patients with CLL/SLL (4% of cases). CNS CLL/RS is a rare condition, and neurologic symptoms in patients with CLL are attributable to other etiologies in w80% of cases. Analysis of the CSF has high sensitivity but limited specificity to distinguish CNS CLL from other etiologies and additional parameters are needed.

Rates of tobacco use are increasing in the regions of Latin America and the Caribbean (LAC). Unfortunately, tobacco cessation education is not a standard component of the dental curriculum in LAC dental schools. The objective of this study was to identify the perceptions of LAC dental faculty members regarding the tobacco use prevention and cessation (TUPAC) competencies that should be addressed in the dental curricula. Dental deans and faculty completed a web-based questionnaire in Spanish, Portuguese, French, or English. The questionnaire contained 32 competencies grouped into the five A's (Ask, Advise, Assess, Assist, and Arrange) of tobacco cessation and six supplementary questions for identifying barriers to providing TUPAC education to dental students. Respondents indicated the degree to which they believed each competency should be incorporated into the dental curricula using a five-point Likert scale (“1” = strongly disagree to “5” = strongly agree). Responses were obtained from 390 faculty members (66 % South America, 18 % Mexico/Central America, 16 % the Caribbean). Of the respondents, 2, 12, and 83 % reported that smoking was allowed in clinical environments, other indoor environments, and outdoor environments of their dental schools, respectively. Mean importance ratings for each of the competencies were as follows: Ask (4.71), Advise (4.54), Assess (4.41), Assist (4.07), and Arrange (4.01). Overall, LAC dental educators agree that TUPAC training should be incorporated into the dental curricula. Assist and Arrange competencies were rated lower, relative to other competencies. Tobacco use among dental educators and high rates of on-campus smoking could potentially pose barriers to promoting cessation interventions in the LAC dental schools.

Chemotherapy produces extended remissions, and potential cures, in a small minority of patients with acute myeloid leukemia (AML). We explored whether potentially cured patients were at increased risk of subsequent invasive cancer and were able to return to work. Potentially cured patients were defined as those in first or second complete remission (CR) for at least 3 years based on hazard rates for recurrence or death in CR, which declined sharply after this time. Patients who received allogeneic marrow transplant were excluded. We used questionnaires, phone contact, and chart review to obtain information about subsequent cancer and work status. The number of patients who developed invasive cancer was compared with the number expected based on age, gender, and years of follow-up using the Connecticut Tumor Registry. A total of 215 patients met our criteria for potential cure: 203 in first CR and 12 in second CR (of 1,663 treated between 1965 and December, 1992). At a median of 9.2 years from first or second CR, 163 (76%) remain alive in CR. Fifteen patients developed 18 invasive cancers (expected number of patients, 8.8; observed/expected, 1.70; 95% CI, 0.96 to 2.84; P = .06). Patients initially treated between 1973 to 1979, patients above the potentially cured cohort's median age of 40 years, and those who presented with abnormalities of chromosomes 5 and/or 7 were more likely to develop subsequent cancer, whereas the observed/expected ratio for younger patients was 1.05 (95% CI, 0.13 to 3.80; P = .56). Seventy-four percent of the patients who were working full-time and who were under age 50 at time of treatment for AML have been working full-time in the last 6 months. Only 17 of 56 patients who are currently not working cited physical limitation as the reason. Patients with potentially cured AML are likely to be able to return to work, and at least if younger do not, on average, have an increased risk of invasive cancer.

BACKGROUND Chemotherapy is known to cure a small minority of patients with acute myeloid leukemia (AML). Less is known about the risk of such patients developing subsequent cancers or about their ability to return to work. METHODS The authors analyzed outcomes among 1892 patients who received treatment for newly diagnosed AML at the University of Texas M. D. Anderson Cancer Center from 1965 to May 1995. RESULTS Because failure rates declined to relatively low levels after a first or later complete remission of ≥3 years' duration, such patients comprised a "potentially cured" cohort. The criterion for entry into this cohort was fulfilled by 215 patients (10.7%; 203 in first complete remission and 12 in second remission). At a median of 6.2 years after entry into the cohort (i.e., 9.2 years from complete remission), 163 patients (76%) remain alive and in complete remission. Approximately 9% and 5% of the 1892 patients have been in complete remission for >5 years and >10 years, respectively. The pretreatment prognostic importance of cytogenetics is still apparent even after 5 years in complete remission. On average, members of the potentially cured cohort were not observed to be at increased risk of subsequent invasive malignancies compared with a normal population. Furthermore, two-thirds of those in the potentially cured cohort who were working full time before diagnosis of AML claimed to have returned to full-time work. Of those not working, only 10% cited physical limitation as the reason. CONCLUSIONS The major threat to the life and well-being of the patient with AML is clearly the disease and not its treatment. Cancer 1997; 80:2176-80. © 1997 American Cancer Society.

Saline breast implants have been used for the past 30 years for cosmetic and reconstructive purposes. Data based on a large number of patients are needed to evaluate patient satisfaction, cancer screening practices, problems associated with breast-feeding, and health effects. We conducted a follow-up study of 292 cosmetic saline breast implant patients from Texas and Louisiana who consented to a telephone nit

Nonmelanoma skin cancer (NMSC) is the most common type of cancer in the US white population. In 1996 more than 800,000 new cases are expected to be diagnosed in the United States, constituting more than one third of all new cancer cases expected. The two principal histologic types of NMSC are basal cell carcinoma and squamous cell carcinoma. These two types account for approximately 75% and 25% of all NMSC cases, respectively. This article reviews the complex interactions between host factors such as race and age, and environmental factors such as lifetime sun and radiation exposure that determine individual risk of NMSC.

Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values, Author Summary Central obesity is a marker of body fat distribution and is known to have a genetic underpinning. Few studies have reported genome-wide association study (GWAS) results among individuals of predominantly African ancestry (AA). We performed a collaborative meta-analysis in order to identify genetic loci associated with body fat distribution in AA individuals using waist circumference (WC) and waist to hip ratio (WHR) as measures of fat distribution, with and without adjustment for body mass index (BMI). We uncovered 2 genetic loci potentially associated with fat distribution: LHX2 in association with WC-adjusted-for-BMI and at RREB1 for WHR-adjusted-for-BMI. Six of fourteen previously reported loci for waist in EA populations were significant in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). These findings reinforce the concept that there are loci for body fat distribution that are independent of generalized adiposity.

Myelodysplastic syndromes (MDS) prognosis is currently based solely on clinical parameters. The identification of additional factors associated with MDS outcome could be used to further improve the current scoring system such as the International Prognostic Scoring System (IPSS). The present study evaluates the role of epidemiological markers as predictors of survival for 365 adult de novo MDS patients. Multivariable Cox regression analysis was used to estimate overall survival. Median follow-up time was 22 months. At the time of last follow-up, 271 patients (74.3 %) had died. For all MDS patients, medium-high lifetime occupational agrochemical exposure (HR 1.85, CI 1.19-2.89) remained as an independent predictor of MDS survival. Stratified analysis by gender showed that ≥ 25 pack-years smoked (HR 1.44, CI 1.001-2.09) and medium-high lifetime occupational agrochemical exposure (HR 1.84, CI 1.15-2.97) were independent predictors of MDS survival in men, but not in women. For MDS patients stratified by IPSS categories, ≥ 25 pack-years smoked (HR 1.75, CI 1.005-3.06) was an independent predictor for intermediate 1 IPSS risk group only, and medium-high lifetime occupational agrochemical exposure was associated with increased mortality (HR 4.36, CI 1.20-15.8) in the high IPSS risk group. Smoking and lifetime occupational agrochemical exposure may play a role in MDS survival. Incorporating relevant epidemiological markers with known clinical predictors of outcome may help physician stratify patients and customize treatment strategies to improve the outcome of MDS.

Prostate cancer (CaP) is the leading cancer among men of African descent in the USA, Caribbean, and Sub-Saharan Africa (SSA). The estimated number of CaP deaths in SSA during 2008 was more than five times that among African Americans and is expected to double in Africa by 2030. We summarize publicly available CaP data and collected data from the men of African descent and Carcinoma of the Prostate (MADCaP) Consortium and the African Caribbean Cancer Consortium (AC3) to evaluate CaP incidence and mortality in men of African descent worldwide. CaP incidence and mortality are highest in men of African descent in the USA and the Caribbean. Tumor stage and grade were highest in SSA. We report a higher proportion of T1 stage prostate tumors in countries with greater percent gross domestic product spent on health care and physicians per 100,000 persons. We also observed that regions with a higher proportion of advanced tumors reported lower mortality rates. This finding suggests that CaP is underdiagnosed and/or underreported in SSA men. Nonetheless, CaP incidence and mortality represent a significant public health problem in men of African descent around the world.

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10-14), 18q21.33 (BCL2, P = 7.76 × 10-11), 11p15.5 (C11orf21, P = 2.15 × 10 -10), 4q25 (LEF1, P = 4.24 × 10-10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10-9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10-8), 18q21.32 (PMAIP1, P = 2.51 × 10 -8), 15q15.1 (BMF, P = 2.71 × 10-10) and 2p22.2 (QPCT, P = 1.68 × 10-8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10-18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10-8) and 5p15.33 (TERT, P = 1.92 × 10-7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism. © 2013 Nature America, Inc. All rights reserved.

BACKGROUND Little is known regarding racial disparities in characteristics and outcomes among patients with chronic lymphocytic leukemia (CLL). METHODS The characteristics and outcomes of untreated African American (AA) patients with CLL (n = 84) were analyzed and compared with a reference nonblack (NB) patient population (n = 1571). RESULTS At the time of presentation, AA patients had lower median hemoglobin levels (12.9 g/dL vs 13.7 g/dL), higher β2 microglobulin levels (2.7 mg/dL vs 2.4 mg/dL), greater frequency of constitutional symptoms (27% vs 10%), unmutated immunoglobulin heavy-chain variable region (IGHV) mutation status (65% vs 47%), ζ-chain–associated protein kinase 70 (ZAP70) expression (58% vs 32%), and deletion of chromosome 17p or chromosome 11q (28% vs 17%; P ≤ 02 for each comparison). Fifty-one percent of AA patients and 39% of NB patients required first-line therapy and 91% and 88%, respectively, received chemoimmunotherapy. Overall response rates to treatment were 85% for AA patients and 94% for NB patients (P = .06); and the complete response rates were 56% and 58%, respectively (P = .87). The median survival of AA patients was shorter compared with that of NB patients (event-free survival: 36 months vs 61 months; P = .007; overall survival: 152 months vs not reached; P = .0001). AA race was an independent predictor of shorter event-free and overall survival in multivariable regression models. CONCLUSIONS The current results indicated that AA patients with CLL have more unfavorable prognostic characteristics and shorter survival compared with their NB counterparts. Cancer 2013;119:3177–3185. © 2013 American Cancer Society.

We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10−16). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

This study was conducted to explore whether racial/ethnic differences exist in treatment discussed, preferred and ultimately received for localized PCa as epidemiological data are scant on this issue. We recruited 640 localized PCa patients from the Texas Medical Center, Houston, TX, between 1996 and 2004. We used a structured questionnaire to collect data through personal interviews. Three main treatment modalities for localized PCa, consisting of surgery, radiation therapy and watchful waiting, were considered for this study. We found that health professionals were less likely to discuss surgery (OR=0.35, 95% CI= 0.18–0.68) and watchful waiting (OR=0.53, 95% CI= 0.34–0.83) with Hispanics than whites. Whereas, African Americans were less likely to receive watchful waiting (OR=0.22, 95% CI= 0.05–0.93). They were more likely to prefer (OR=1.23, 95% CI= 0.78–1.94) and receive (OR=1.27, 95% CI= 0.87–1.86) radiation therapy, although, they didn’t achieve statistical significance (p

Owing to their role in controlling the efflux of toxic compounds, transporters are central players in the process of detoxification and elimination of xenobiotics, which in turn is related to cancer risk. Among these transporters, ATP-binding cassette B1/multidrug resistance 1 (ABCB1/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP) affect susceptibility to many hematopoietic malignancies. The maintenance of regulated expression of these transporters is governed through the activation of intracellular "xenosensors" like the nuclear receptor 1I2/pregnane X receptor (NR1I2/PXR). SNPs in genes encoding these regulators have also been implicated in the risk of several cancers. Using a tagging approach, we tested the hypothesis that common polymorphisms in the transporter genes ABCB1, ABCC2, ABCG2 and the regulator gene NR1I2 could be implicated in lymphoma risk. We selected 68 SNPs in the four genes, and we genotyped them in 1,481 lymphoma cases and 1,491 controls of the European case-control study (EpiLymph) using the Illumina GoldenGate® assay technology. Carriers of the SNP rs6857600 minor allele in ABCG2 was associated with a decrease in risk of B-cell lymphoma (B-NHL) overall (p < 0.001). Furthermore, a decreased risk of chronic lymphocytic leukemia (CLL) was associated with the ABCG2 rs2231142 variant (p = 0.0004), which could be replicated in an independent population. These results suggest a role for this gene in B-NHL susceptibility, especially for CLL. Copyright © 2011 UICC.

Background . Inherited polymorphisms of DNA repair genes may contribute to genetic susceptibility to squamous cell carcinoma of the head and neck (SCCHN). The objective was to assess whether two polymorphisms in the nucleotide excision repair gene XPD ( ERCC2 ) are markers of SCCHN risk. Methods . We performed a hospital-based case-control study of 180 SCCHN patients and 400 cancer-free controls frequency matched on age, sex, smoking, and alcohol use. All subjects were non-Hispanic whites. XPD alleles 23047 and 23051 were assessed by digestion with the restriction enzymes Xho II and Sph I after PCR amplification. Results . The XPD 23047 G and XPD 23051 T alleles were extremely rare among both the cases and controls (allele frequencies P >0.6). Conclusions . The 23047 and 23051 variants of the DNA repair gene XPD are extremely rare and do not contribute significantly to the risk of SCCHN in the non-Hispanic white population.

Male Hi-Myc mice were placed on three dietary regimens [30% calorie restriction (CR), overweight control (modified AIN76A with 10 kcal% fat), and a diet-induced obesity regimen (DIO) 60 kcal% fat]. All diet groups had approximately similar incidence of hyperplasia and low-grade prostatic intraepithelial neoplasia in the ventral prostate at 3 and 6 months of age. However, 30% CR significantly reduced the incidence of in situ adenocarcinomas at 3 months compared with the DIO group and at 6 months compared with both the overweight control and DIO groups. Furthermore, the DIO regimen significantly increased the incidence of adenocarcinoma with aggressive stromal invasion, as compared with the overweight control group (96% vs. 65%, respectively; P = 0.02) at the 6-month time point. In addition, at both 3 and 6 months, only in situ carcinomas were observed in mice maintained on the 30% CR diet. Relative to overweight control, DIO increased whereas 30% CR reduced activation of Akt, mTORC1, STAT3, and NFκB (p65) in ventral prostate. DIO also significantly increased (and 30% CR decreased) numbers of T-lymphocytes and macrophages in the ventral prostate compared with overweight control. The mRNA levels for interleukin (IL) 1α, IL1β, IL6, IL7, IL23, IL27, NFκB1 (p50), TNFα, and VEGF family members were significantly increased in the ventral prostate of the DIO group compared with both the overweight control and 30% CR diet groups. Collectively, these findings suggest that enhanced growth factor (Akt/mTORC1 and STAT3) and inflammatory (NFκB and cytokines) signaling may play a role in dietary energy balance effects on prostate cancer progression in Hi-Myc mice. Cancer Prev Res; 4(12); 2002–14. ©2011 AACR.

Success of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has given patients hope for a long disease-free-survival. A longer survival raises the question of late effects, including development of another malignancy. Records of 1445 patients with CML/myeloproliferative neoplasm or other hematologic malignancies treated with TKIs were reviewed to investigate frequency and characteristics of second malignancies (other than acute myeloid leukemia, acute lymphocytic leukemia, or myelodysplastic syndrome). The number of second cancers was compared with the number expected from the Surveillance, Epidemiology, and End Results database. After a median follow-up of 107 months (range, 13-362 months) after CML/myeloproliferative neoplasm diagnosis, 66 patients (4.6%) developed 80 second cancers, including skin (31%), prostate (15%), melanoma (13%), digestive system (10%), kidney (4%), thyroid (4%), breast (3%), chronic lymphocytic leukemia (3%), hepatobiliary (3%), and other cancers (14%). Excluding nonmelanoma skin cancers, 55 second cancers were seen in 51 (3.5%) of all patients treated. The risk of second cancer was lower than expected (observed-to-expected ratio, 0.6; 95% confidence interval, 0.44-0.81). Second cancers occur in a small percentage of patients receiving therapy with TKIs for hematologic malignancies, mostly CML. No evidence at the moment suggests that exposure to TKIs increases the risk of developing second cancers.

Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value

Monoclonal B-cell lymphocytosis (MBL) is a hematologic condition wherein small B-cell clones can be detected in the blood of asymptomatic individuals. Most MBL have an immunophenotype similar to chronic lymphocytic leukemia (CLL), and 'CLL-like' MBL is a precursor to CLL. We used flow cytometry to identify MBL from unaffected members of CLL kindreds. We identified 101 MBL cases from 622 study subjects; of these, 82 individuals with MBL were further characterized. In all, 91 unique MBL clones were detected: 73 CLL-like MBL (CD5(+)CD20(dim)sIg(dim)), 11 atypical MBL (CD5(+)CD20(+)sIg(+)) and 7 CD5(neg) MBL (CD5(neg)CD20(+)sIg(neg)). Extended immunophenotypic characterization of these MBL subtypes was performed, and significant differences in cell surface expression of CD23, CD49d, CD79b and FMC-7 were observed among the groups. Markers of risk in CLL such as CD38, ZAP70 and CD49d were infrequently expressed in CLL-like MBL, but were expressed in the majority of atypical MBL. Interphase cytogenetics was performed in 35 MBL cases, and del 13q14 was most common (22/30 CLL-like MBL cases). Gene expression analysis using oligonucleotide arrays was performed on seven CLL-like MBL, and showed activation of B-cell receptor associated pathways. Our findings underscore the diversity of MBL subtypes and further clarify the relationship between MBL and other lymphoproliferative disorders.

Background: This study was carried out to identify racial/ethnic differences in predictors of prostate-specific antigen (PSA) screening in a group of prostate cancer patients. Methods: In this cross-sectional study, a total of 935 prostate cancer patients were recruited from the Texas Medical Center, Houston, between 1996 and 2004. It included 372 Caucasians, 346 African Americans and 217 Hispanics. A structured questionnaire was used to collect data on socio-demographic and life-style related variables, and self-reported PSA screening history through personal interview. Results: African American (54.4%) and Hispanic patients (42.3%) were significantly less likely (p=0.004 and p

The occurrence of cancer and neurological disorders in first- and second-degree relatives of children in the United States and Canada diagnosed with brain tumor before age six was investigated. A pair-matched case-control study with 155 astrocytoma and 166 primitive neuroectodermal tumor (PNET) cases was performed. Cases were identified through the Childrens Cancer Group. Controls were selected by random-digit dialing and matched to cases on age, race, and telephone area code and exchange. Childhood cancers were more common in PNET relatives compared with the general population (standardized incidence ratio [SIR] = 2.5, 95 percent confidence interval [CI] 1.1-4.8, P = 0.02) and with control relatives (odds ratio [OR] = 3.0, CI = 0.5-30, P = 0.29). For astrocytoma, nonsignificant excesses of brain tumor, leukemia/lymphoma, and childhood cancer occurred among case relatives compared with control relatives, but not compared with the general population. Astrocytoma cases were significantly more likely than controls to have a relative with seizures (OR = 2.5, CI = 1.2-4.9, P = 0.009), especially childhood seizures (OR = 3.4, CI = 1.2-12, P = 0.02), epilepsy (OR = 3.0, CI = 0.9-13, P = 0.08), and febrile convulsions (OR = 4.5, CI = 0.9-43, P = 0.07). A family history of stroke was not a risk factor for either type of brain tumor. These results suggest that some childhood brain tumors may result from a genetic susceptibility and that some risk factors may affect childhood astrocytoma and PNET differently.

Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values ≤ 3.37 × 10−8), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 × 10−9). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies.