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International audience; Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

In the version of this article originally published, the names of the equally contributing authors and jointly supervising authors were switched. The correct affiliations are: “These authors contributed equally: David V. Conti, Burcu F. Darst. These authors jointly supervised this work: David V. Conti, Rosalind A. Eeles, Zsofia Kote-Jarai, Christopher A. Haiman.” The error has been corrected in the HTML and PDF versions of the article.

Purpose Independent and combined effects of air pollution and psychosocial stressors on hypertension, a risk factor for cardiovascular disease, among Hispanics are not well studied. Methods We administered a pilot-tested questionnaire on individual- and neighborhood-level psychosocial stressors, developed with community input, to nearly 2500 individuals from the MD Anderson Cancer Center cohort of Mexican-Americans. We used data from local air quality monitors to estimate individual exposures to ozone (O3) and fine particulate matter (PM2.5) for the 12-month period preceding enrollment using inverse distance interpolation. We applied logistic regression models to examine relationships between exposures to psychosocial stressors and air pollution with prevalent hypertension and used stratified analyses to examine the interacting effects of these two exposures on hypertension. RESULTS: There was a positive association between prevalent hypertension and a high frequency of feeling anxious or depressed (prevalence odds ratio (POR) = 1.36, 95% CI [1.06-1.75]) and experiencing aches and pains (POR = 1.29, 95% CI [1.01-1.64]). The odds of having hypertension were also elevated among those worrying about their own health (POR = 1.65, 95% CI [1.30-2.06]) or about not having enough money (POR = 1.27, 95% CI [1.01-1.6]). We observed an inverse association between O3 and hypertension. There was no interaction between psychosocial stressors and O3 on hypertension. Conclusion Our findings add to the evidence of a positive association between individual and family stressors on hypertension among Hispanics and other racial/ethnic groups. Contrary to previous studies reporting positive associations, our results suggest that long-term exposure to O3 may be inversely related to prevalent hypertension.

Latinos represent, What's new? There is strong evidence for a genetic predisposition to prostate cancer (PrCa). Most of this information has come from European ancestry populations, with Latinos representing less than 1% of samples in cancer genome‐wide association studies (GWAS). In this study, the majority of established PrCa risk variants (83.3%) were consistently associated with PrCa risk in Latinos. A polygenic risk score comprised of GWAS‐identified risk variants could identify 10% of Latino men with a ~three‐fold increase in PrCa risk. These findings suggest that common germline variants for PrCa can stratify risk in Latino men, which has implications for targeted screening and prevention.

The optimum use of androgen deprivation therapy (ADT) in high-risk prostate cancer patients has not been defined in the setting of dose-escalated external beam radiation therapy. A retrospective analysis of 1,290 patients with high-risk prostate cancer from June 1987 through March 2010 treated with external beam radiation therapy was performed. Median follow-up was 7.2 years, and 797 patients received ADT, with 384 patients experiencing a biochemical failure and 145 with distant metastasis. ADT was associated with lower risk of biochemical failure and distant metastasis than no ADT after adjusting for age, prostate-specific antigen (PSA), Gleason score, year of diagnosis, tumor stage, and radiation dose. ADT was associated with a greater reduction in biochemical failure in the low-dose radiation group than in the high-dose group. Patients with >24 months of ADT had a lower risk of PSA failures than those with 24 months of ADT in all patients who received ADT.

To better characterize the relation of acculturation, based on language use, to smoking status among Mexican-Americans, a large study sample from an ongoing cohort of Mexican-American households in Texas was stratified into current smokers and non-smokers. Four language-use groups were created based on Low/High use of Spanish and English, representing different degrees of acculturation. Participants who reported high English but low Spanish use had the highest smoking prevalence (20.1 %), followed by High English/High Spanish (13.6 %), Low English/High Spanish (8.7 %), and Low English/Low Spanish (6.4 %). Current smokers were more likely to be male, have lower than high school education, currently consume alcohol or had consumed alcohol but quit, and report low Spanish/high English use. Consistent with recent models of acculturation, individuals can differ both in their maintenance of the native language and adoption of a new language and both dimensions are important in predicting tobacco use.

Comprehensive analysis of factors impacting risks and outcomes of therapy-related myeloid neoplasms following breast cancer treatment

Summary Background Tyrosine-kinase inhibitors improve overall survival in patients with chronic myeloid leukaemia in chronic phase (CML-CP). Survival compared with the general population by age, response, and type of tyrosine-kinase inhibitor is not known. With use of data from trials of tyrosine kinase inhibitors, we compared overall survival in patients with newly diagnosed CML-CP to that of general population. Methods In this cohort analysis, we included data from patients with CML-CP enrolled in six consecutive or parallel prospective clinical trials of tyrosine-kinase inhibitors at a single institution from July 30, 2000, to Sept 17, 2012. We analysed data for response and survival with the Kaplan-Meier method. For estimated overall survival in the general population, we obtained data from national vital statistics reports and matched to patients with CML-CP by age, sex, ethnicity, and year at diagnosis. We assessed numbers and causes of death within 1 year of beginning treatment by age group and by response to therapy. We then did univariate analysis and multivariate analysis to investigate factors associated with survival probability. Findings Our analysis included 483 patients, 271 received imatinib, 105 received nilotinib, and 107 received dasatinib. Most patients were younger than 65 years, and no patients were older than 85 years. Median follow-up was 99·4 months (IQR 44·9–121·6), by which time 53 (11%) patients had died. The most common causes of death were progression to advanced disease stage, including complications of stem-cell transplantation (17 [4%] patients), secondary malignancies (nine [2%] patients), and cardiovascular causes (nine [2%] patients). 5-year overall survival in patients with CML-CP decreased in older age categories. For the whole population of patients with CML-CP, 5-year survival was only slightly lower than that of the matched general population (relative survival 94·7% [95% 92·1–97·4]). Individuals of all ages with a report of complete cytogenetic response to treatment or deeper within 1 year had a 5-year survival similar to that of the general population. Interpretation In the era of treatment with tyrosine-kinase inhibitors, patients diagnosed with CML-CP can expect a 5-year survival that is only slightly lower than that of the general population. With access to tyrosine-kinase inhibitors, most patients with chronic myeloid leukaemia could enjoy a near normal life expectancy. Funding MD Anderson Cancer Center, National Cancer Institute.

Background: The interplay between metabolic syndrome (MetS) and race/ethnicity on prostate specific antigen (PSA) still remains unclear. The three major definitions of MetS (National Cholesterol Education Program [ATP III], International Diabetes Federation [IDF], and World Health Organization [WHO]) differ in number and type of components, which are linked to race/ethnicity. We proposed to investigate the associations of three major definitions of metabolic syndrome with PSA levels, and to determine whether these associations vary by race and ethnicity. Methods: We used measurements of serum PSA levels (ng/mL) in 3528 adult men >40 years from the National Health and Nutrition Examination Survey 2001–2006. MetS was defined using ATP III, IDF, and WHO criteria. Racial/ethnic groups included non-Hispanic blacks (NHBs), non-Hispanic whites (NHWs), and Mexican Americans (MAs). We computed geometric mean PSA levels from weighted multiple linear regression models. Results: Men classified with MetS-ATP ...

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10−12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10−10). At 13q34, the signal is located 5’ of the gene IRS2 and 3’ of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

Serum testosterone is a potential marker to distinguish between indolent and aggressive prostate cancer (PCa). The present study aimed to investigate whether low levels of total serum testosterone at diagnosis were associated with aggressive PCa and poor clinical outcomes. In total, 762 non-Hispanic Caucasian men with previously untreated PCa were recruited from The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients were categorized into three groups based on their total serum testosterone levels according to clinical guidelines [low (350 ng/dl)]. PCa aggressiveness (low-, intermediate- or high-risk, or metastatic) was compared using multinomial logistic regression. Rates of disease progression, mortality from any cause and PCa-specific mortality were compared using the multivariate Cox proportional hazards model. Testosterone levels significantly decreased as PCa aggressiveness increased (P

Diet has been identified as a risk factor for some cancers, but its role in adult de novo acute myeloid leukemia (AML) is unclear. This study was conducted at the University of Texas MD Anderson Cancer Center to evaluate associations between consumption of vegetables, fruits, and meats with AML risk among Texas residents. All participants, 323 adult de novo AML cases and 380 frequency-matched controls, completed demographic and food frequency questionnaires. Overall, AML risk was significantly decreased among those who consumed the most dark green vegetables, seafood, and nuts/seeds; and it was significantly increased among greatest consumers of red meat. Among men, AML risk was lowest among those whose consumption was in the highest quartile for fruits [odds ratio (OR) = 0.25, 95% confidence interval (CI) = 0.10-0.69], poultry (OR = 0.28, 95%CI = 0.10-0.78), and seafood (OR = 0.39, 95%CI = 0.16-0.96) compared to those in the lowest. Among women, risk was lowest among those whose consumption was in the highest quartile of dark-green vegetables (OR = 0.28, 95%CI = 0.12-.68), orange vegetables (OR = 0.40, 95%CI = 0.17-.96) and nuts/beans (OR = 0.26, 95%CI = 0.11-0.60). Based on these findings, interventions can be developed to modify intake of specific dietary components to reduce cancer risk.

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

BACKGROUND Information on the impact of other cancers (OCs) in long-term survivors (LTSs) of chronic lymphocytic leukemia (CLL) is limited. PATIENTS AND METHODS Patients with CLL who survived >10 years were defined as LTSs of CLL. We calculated standardized incidence ratios (SIRs) to compare the incidence of OC in LTS of CLL versus the general population. A multivariable model was used to identify independent predictors of OC. Overall survival was analyzed as a function of the presence of OC. RESULTS Among 797 LTSs of CLL, the cumulative frequency of OC was 36%, similar between 570 patients (72%) who required treatment for CLL (TRT) and 227 (28%) who remained untreated (UT). The most common OC in both groups was non-melanoma skin cancer, followed by prostate cancer, breast cancer, melanoma, lung cancer, and leukemia in TRT patients, and by prostate cancer, breast cancer, melanoma, lung cancer, and gastrointestinal tumors in the UT group. The SIR for all OC was 1.2 (P = 0.034). It was higher in males (SIR 1.31; P = 0.013) and patients

BACKGROUND: Acute myeloid leukemia (AML) is comprised of several bone marrow-based cancers and is the most common type of leukemia in the United States. The etiology of AML is not well understood. A case-control study was conducted at The University of Texas M. D. Anderson Cancer Center to investigate associations between lifestyle characteristics and the risk of AML in Texas. METHODS: This study included 638 adult patients with de novo AML (cases) and a group of 636 matched controls. Interviewer-administered questionnaires were used to collect demographic and occupational data. The distribution of cases by World Health Organization (WHO) subtype was 71 patients (11%) with recurrent cytogenetic abnormalities (AML-RCA), 134 patients (21%) with multilineage dysplasia (AML-MD), and 389 patients (61%) with AML not otherwise categorized (AML-NOC). Multivariate logistic regression analyses were performed among all AML cases and among both sexes and each WHO subgroup. RESULTS: Among men, heavy smoking (≥30 pack-years; odds ratio [OR], 1.86) and occupational solvent exposure at low levels (OR, 2.87) or moderate/high levels (OR, 4.13) statistically significantly increased the risk of AML. Among women, obesity (OR, 1.62) and solvent exposure to low levels (OR, 2.73) or moderate/high levels (OR, 3.90) increased the risk of AML. Across WHO subtypes, obesity was associated with a statistically significantly increased risk of AML-RCA (OR, 3.15), whereas solvent exposure increased the risk in all subtypes at low levels (AML-RCA: OR, 4.11; AML-MD: OR, 2.54) and moderate/high levels (AML-RCA: OR, 5.13; AML-MD: OR, 3.02). A joint effect between smoking and solvent exposure was observed, and the highest risk was observed among smokers who had solvent exposure (OR, 4.51). CONCLUSIONS: The current results suggested that several factors play a role in AML predisposition with possible joint effects. Risk profiles for AML differed by sex and WHO subtype. Cancer 2012. © 2012 American Cancer Society.

Background Patients may delay treatment for skin cancer for various reasons. Prior research on treatment delay has focused on melanoma rather than nonmelanoma skin cancer (NMSC), which is much more common. Objective We sought to clarify the reasons for delay in the presentation for diagnosis and treatment of NMSC. Methods This was a prospective cohort study in a Mohs micrographic surgery private practice in an urban setting. Eligible subjects were 982 consecutive patients presenting for Mohs micrographic surgery for NMSC between March and December 2005. No enrolled subjects were withdrawn for adverse effects. The survey was a 4-page written self-administered questionnaire, eliciting patient medical history, skin cancer history, demographic information, initial and subsequent lesion size, and reasons for delay in presentation for evaluation and management. Outcome analyses addressed the: (1) frequency of specific reasons for delayed presentation, as provided by self-report; (2) association between reasons for delay with demographic or other patient-specific factors; and (3) change in lesion diameter from the time of detection by the patient to the time of presentation to the doctor. Results Among the reasons for waiting, denial (including: thought it would go away, thought it wasn't important, too busy, thought they could self-treat, afraid it might be something dangerous) was the most frequent, accounting for 71% of cases; difficulty scheduling was associated with 10% of the instances of delay. Older patients (age >64 years) were more likely to wait to seek care than younger patients (odd ratio [OR] = 0.5; 95% confidence interval [CI] 0.4-0.7). Patients with a prior skin cancer were more likely to wait (OR = 1.4; 95% CI 1.1-2.0), as were patients with major life problems (OR = 2.6; 95% CI 1.6-4.3) and patients with a history of any cancer (OR = 1.8; 95% CI 1.3-2.4). Weighted kappa analysis comparing tumor size at the two time points yielded a kappa of 0.72 (SE = .02; 95% CI 0.68-0.77). When the data were separated into two groups, one including those tumors that had decreased in size or remained the same (698 patients), and those that had increased in size (120 patients), the median delay-to-presentation intervals associated with these two groups (2.5 vs 6.0 months, respectively) were found to be significantly different ( P Limitations This study may have limited generalizability to the extent that it reflects the characteristics only of the subpopulation of patients with skin cancer who eventually received treatment at a referral-based, urban, dermatology private practice. Overall, these patients may have been better insured and be more affluent than the general population. Conclusions Denial is the most common patient-specific factor accounting for delayed presentation for NMSC diagnosis and treatment. Patients younger than 65 years, with a skin cancer history, with major life problems, and with a history of any cancer were most likely to wait to see a doctor. There was a significant increase in tumor size from the time when tumors were noticed by patients to the time when patients presented to a physician. Increased delay was associated with increased tumor growth.

Androgen levels during critical periods of testicular development may be involved in the aetiology of testicular germ cell tumours (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case-control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls [odds ratio (OR): 0.6; 95% confidence interval (CI): 0.4, 1.0]. Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR: 0.5; 95% CI: 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with a decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake.

Gastrointestinal stromal tumor (GIST) is a rare cancer of the digestive tract that accounts for 0.1%–3.0% of all gastrointestinal neoplasms, 10% of small-bowel tumors, and 10%–15% of all sarcomas [1–4]. There are ∼5000 newly diagnosed cases per year in the USA. Although most of these cases are sporadic, there are reported syndromes of autosomal dominant hereditary GIST that result from inheritance of a germ-line KIT or platelet-derived growth factor receptor (PDGFR) mutation [5]. Additionally, there are predisposition syndromes in which affected individuals may develop GIST as well as other types of cancer. Examples include malignant peripheral nerve sheath tumor in neurofibromatosis [6], paraganglioma and pulmonary chondroma in Carney’s triad [7], and paraganglioma in the Carney–Stratakis syndrome [8]. Recently, Agaimy et al. [9] found that the most common association with GIST is gastric carcinoma (47%), prostate cancer (9%), lymphoma/leukemia (7%), and breast cancer (7%). Au et al. [10] reported that GIST and papillary renal cell carcinoma may occur as familial tumors related to mutations in the proto-oncogenes c-MET and c-KIT. An association has been demonstrated between GIST and acute myeloid leukemia (AML) as well as chronic myelogenous leukemia [11]. The clinical use of imatinib mesylate (imatinib), an oral inhibitor of the Kit receptor tyrosine kinase, has increased the survival of patients with metastatic GIST [12]. Due to the marked success of imatinib in both the adjuvant primary and the metastatic settings, many patients with GIST are treated with imatinib for many years. There are limited data as to the occurrence of additional malignancies after diagnosis of GIST in patients treated with imatinib. Thus, it is critical to investigate the prevalence and type of malignancies that develop before and after diagnosis in the era of increasing use of imatinib for GIST. In this study, we used the University of Texas M. D. Anderson Cancer Center (MDACC) cancer registry to identify additional primary malignancies among our patients with GIST. Furthermore, we have rigorously determined detailed patient demographics, histological type of all malignancies, and whether these additional cancers occurred before or after the diagnosis of GIST. Finally, we estimated the survival of patients with GIST with none, one, or multiple other primary tumors.

What's known on the subject? and What does the study add? Scientists have found a number of genetic factors that increase prostate cancer risk, including heritable mutations in the genes BRCA1 and BRCA2. These mutations are not common but can have major impact, as a BRCA2 mutation increases risk by up to seven-fold while a BRCA1 mutation is thought to double risk in men under 65. The IMPACT study aims to determine whether targeted screening in men with a known BRCA1 or BRCA2 mutation would lead to earlier diagnosis of prostate cancers. This data from the IMPACT study adds to the increasing evidence that BRCA mutation carriers develop more aggressive disease. Although these are early results, it appears that PSA screening is more accurate at predicting potentially aggressive prostate cancer among men at higher risk of the disease due to a genetic predisposition than general population screening. This study provides support for continued screening in men with genetic mutations. OBJECTIVE To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported. PATIENTS AND METHODS Men aged 40-69 years from families with BRCA1 or BRCA2 mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA > 3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (+/- 5 years) who were negative for the familial mutation. RESULTS In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2 and 95 controls) over 33 months. At the baseline screen (year 1), 7.0% (21/300) underwent a prostate biopsy. Prostate cancer was diagnosed in ten individuals, a prevalence of 3.3%. The positive predictive value of PSA screening in this cohort was 47 center dot 6% (10/21). One prostate cancer was diagnosed at year 2. Of the 11 prostate cancers diagnosed, nine were in mutation carriers, two in controls, and eight were clinically significant. CONCLUSIONS The present study shows that the positive predictive value of PSA screening in BRCA mutation carriers is high and that screening detects clinically significant prostate cancer. These results support the rationale for continued screening in such men.

We performed an in-depth and well-powered investigation of genetic variation across the cancer susceptibility region at chromosome 8q24 (127.6-129.0 Mb) to search for novel risk variants associated with prostate cancer (PCa) risk in the European ancestry population. We combined genotyped and imputed data from the PRACTICAL/ELLIPSE OncoArray and iCOGS consortia consisting of 71,535 PrCa cases and 52,935 controls of European ancestry. Variants with high imputation quality score (>0.8) were retained for a total of 5,600 overlapping variants between the two datasets. Associations of genetic variants with PCa risk were evaluated using unconditional logistic regression with adjustment for country and ten principal components. The marginal risk estimates for the 5,600 variants that passed quality control were combined by a fixed effects meta-analysis. A meta-stepwise selection was performed on variants marginally associated with PCa risk from the meta results (P Citation Format: Marco Matejcic, Edward J. Saunders, Tokhir Dadaev, Mark Brook, Ali Amin Al Olama, Fredrick R. Schumacher, Sonja I. Berndt, Sara Benlloch, Kenneth Muir, Koveela Govindasami, Victoria L. Stevens, Susan M. Gapstur, Catherine M. Tangen, Jyotsna Batra, Judith Clements, APCB (Australian Prostate Cancer Bio Resource), Henrik Gronberg, Nora Pashayan, Johanna Schleutker, Demetrius Albanes, Alicja Wolk, Catharine West, Lorelei Mucci, Peter Kraft, Géraldine Cancel-Tassin, Stella Koutros, Karina Dalsgaard Sorensen, Lovise Maehle, Eli Marie Grindedal, Sara Strom, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Ruth C. Travis, Robert J. Hamilton, Sue Ann Ingles, Barry Rosenstein, Yong-Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Jeanette Bensen, Manolis Kogevinas, Fredrik Wiklund, Stephen Chanock, Douglas F. Easton, Rosalind A. Eeles, Zsofia Kote-Jarai, David V. Conti, Christopher A. Haiman. Germline variation at 8q24 and prostate cancer risk in men of European ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 227.

Purpose Other malignancies have been reported to occur with increased frequency in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The aim of this study was to determine the frequency, outcomes, and factors associated with other cancers in patients with CLL/SLL. Patients and Methods We reviewed the records of consecutive patients with previously untreated CLL/SLL seen at The University of Texas M. D. Anderson Cancer Center from 1985 to 2005. The number of second cancers observed was compared with the number expected from the Surveillance, Epidemiology, and End Results database. Results Among 2,028 patients, 324 (16%) had a history of other cancers and 227 (11.2%) developed other malignancies during the follow-up period. Overall, 625 cancers were observed in 551 patients, including skin (30%), prostate (13%), breast (9%), melanoma (8%), lymphoma (8%), gastrointestinal (9%), lung (6%), and other cancers (17%). The risk of a second cancer was 2.2 times higher than the expected risk. The response rates in patients with and without a history of other cancers were 86% and 92%, respectively (P = .04), and the 5-year survival rates were 70% and 82%, respectively (P < .001). In Cox analysis, independent factors predicting development of new cancers were older age, male sex, and elevated levels of β2-microglobulin, lactate dehydrogenase, and creatinine. In patients who were treated for CLL/SLL, the treatment regimen did not affect the risk of subsequent cancer (P = .49). Conclusion Patients with CLL/SLL have more than twice the risk of developing a second cancer and an increased frequency of certain cancer types. Awareness of risk factors could permit early detection.

We assessed the expression of Matrix Metalloproteinase (MMP) to E-cadherin (M/E ratio) to determine the correlation of gene expression with pathologic variables and outcome in a cohort of African American (AA) prostate cancer patients.Tumors from formalin-fixed, paraffin embedded RP specimens were examined. Gleason scores were 6, 7, andor=8 in 7, 16, 13 tumors, respectively. Pathologic stage was organ confined (pT2) in 18 and advanced (pT2) in 18 tumors. A colorimetric mRNA in situ hybridization (ISH) assay was performed using biotinylated anti-sense oligonucleotide probes for MMP 2 and 9, as well as for E-cadherin gene transcripts. Immunohistochemistry (IHC) was performed utilizing specific monoclonal antibodies to detect the above genes. Image analysis was performed to determine the intensity of both mRNA and protein expression. Two reviewers analyzed ISH gene expression independently.The M/E expression ratio was significantly increased at the invasive edge (but not the center) of tumors of higher Gleason score (P = 0.02 and 0.0008) and pathologic stage (P = 0.0001 and0.0001) when examined by both ISH and IHC. Significant variability in ISH staining interpretation was noted within and among the two study reviewers. An M/E ratio2.5 was associated with biochemical recurrence after radical prostatectomy in addition to tumor pathologic stage subsequent to univariate statistical analysis.The M/E ratio characterizes an important aspect of the molecular phenotype associated with the histologic progression of prostate cancer among African American prostate cancer patients. A larger comparative study is required to determine potential racial variation and prognostic significance of gene expression.

BACKGROUND There is a paucity of information regarding prostate cancer (PCa) risk factors among Hispanics, the fastest-growing ethnic group in the United States. METHODS This population-based case-control study included 176 Texas men of Mexican descent with PCa and 174 age- and ethnicity-matched controls. Demographic, lifetime occupational history, family history of cancer, lifestyle (e.g., smoking, alcohol, diet, and recreational physical activity) and anthropometric information were collected by personal interviews. Chemical exposure and physical activity were determined using job-exposure matrices for each reported job. RESULTS Logistic regression models adjusted for relevant covariates were used to evaluate their independent effects. Compared to controls, cases were three times more likely to work in jobs with high agrichemical exposure (OR = 3.44, 95% CI 1.84–6.44), and 54% less likely to work in jobs with moderate/high occupational physical activity (OR = 0.46, 95% CI 0.28–0.77). In analyses stratified by stage, cases with organ-confined PCa were three times more likely to have high agrichemical exposure (OR = 3.39, 9%CI 1.68–6.84), and 56% less likely to have moderate/high levels of occupational physical activity (OR = 0.44, 95% CI 0.26–0.76). Increased risk of being diagnosed with advanced PCa was associated with obesity at time of diagnosis (OR = 2.50, 95% CI 1.20–5.20) and high levels of agrichemical exposure (OR = 4.65, 95% CI 1.97–10.97), but not with occupational physical activity. CONCLUSIONS This case-control study, the first conducted in a homogeneous Hispanic population, identified modifiable PCa risk factors, such as physical activity and agrichemical exposure, which may be useful in developing interventions for this understudied population. Prostate 68: 563–570, 2008. © 2008 Wiley-Liss, Inc.

Previous reports show that obesity predicts biochemical failure after treatment for localized prostate cancer. Since obesity is associated with increased fat consumption, we investigated the role that dietary fat intake plays in modulating obesity-related risk of biochemical failure. We evaluated the association between saturated fat intake and biochemical failure among 390 men from a previously described prostatectomy cohort. Participants completed a food frequency questionnaire collecting nutrient information for the year prior to diagnosis. Because fat and energy intake are highly correlated, the residual method was used to adjust fat (total and saturated) intakes for energy. Biochemical-failure-free-survival rates were calculated using the Kaplan–Meier method. Crude and adjusted effects were estimated using Cox proportional hazards models. During a mean follow-up of 70.6 months, 78 men experienced biochemical failure. Men who consumed high- saturated fat (HSF) diets were more likely to experience biochemical failure (p = 0.006) and had significantly shorter biochemical-failure-free-survival than men with low saturated fat (LSF) diets (26.6 vs. 44.7 months, respectively, p = 0.002). After adjusting for obesity and clinical variables, HSF-diet patients were almost twice as likely to experience biochemical failure (hazard ratio = 1.95, p = 0.008) compared to LSF diet patients. Men who were both obese and consumed HSF diets had the shortest biochemical-failure-free-survival (19 months), and nonobese men who consumed LSF diets had the longest biochemical-failure-free-survival (46 months, p < 0.001). Understanding the interplay between modifiable factors, such as diet and obesity, and disease characteristics may lead to the development of behavioral and/or targeted interventions for patients at increased risk of progression. © 2008 Wiley-Liss, Inc.

Purpose To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-α) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC. Patients and Methods Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN-α (3 × 106 U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation. Results At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-α was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities. Conclusion Results of this phase III trial do not support 13cRA plus IFN-α for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.

The UV radiation-mimetic chemical 4-nitroquinoline-1-oxide (4-NQO) is thought to induce squamous cell carcinoma (SCC) similar to those induced by UV radiation in animals. Therefore, we tested the hypothesis that cellular sensitivity to 4-NQO is associated with risk of developing skin cancer in a case-control study of 191 patients with nonmelanoma skin cancer (NMSC; 81 SCC and 110 basal cell carcinoma (BCC)) and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 microM for 24 hours and scored for chromatid breaks in 50 well-spread metaphases. We found that the mean frequency of chromatid breaks per cell (b/c) was significantly higher in the cases (mean+/-SD, 0.46+/-0.43 for SCC and 0.43+/-0.38 for BCC) than in the controls (0.25+/-0.25; P0.001 for both comparisons) and were associated with more-than-twofold increased risk for both SCC and BCC after adjustment for known risk factors. Therefore, our findings support the notion that sensitivity to 4-NQO reflects susceptibility to UV-induced NMSC. However, there is a lack of correlation between UVB-induced b/c and 4-NQO-induced b/c in this study population. Therefore, these findings need to be verified by additional studies.

Hypertension is on the rise among Hispanics and is highest among those of Mexican origin. Recent studies have found a positive association between air pollution and blood pressure and hypertension. Moreover, a link between hypertension and adverse socioeconomic conditions is well established. However, less is known about psychosocial stressors, although their impact on coronary heart disease has been shown. To address this gap in the literature, community perspectives of the health consequences of environmental exposures and psychosocial stressors experienced among the Mexican-origin population in Houston, Texas were obtained through participation in focus groups, the establishment of a Neighborhood Council of Advisors (NCA), and the testing of a pilot questionnaire. Taken together, the findings from the community were used to develop a culturally sensitive, bilingual questionnaire for an investigation of the combined effects of environmental and psychosocial stressors on hypertension among individuals of Mexican origin.

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.

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].

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)

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.

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.

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.

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.