Genetic determinants for the racial disparities in the risk of prostate and testicular cancers.

BACKGROUND: A worldwide higher incidence of prostate cancer and lower incidence of testicular cancer in men of African ancestry compared to European ancestry has been observed previously. However, underlying mechanisms accounting for these observations are largely unknown. METHODS: The current study analyzed previously reported SNPs associated with either prostate cancer or testicular cancer to examine whether the risk allele frequency could help us understand the observed incidence disparities in men of African ancestry and European ancestry. Both t-test and regression analysis were performed. RESULTS: Here we show that men of African ancestry are more likely to have risk alleles of prostate cancer and less likely to have risk alleles of testicular cancer compared to men of European ancestry. CONCLUSIONS: Our findings suggest that genetic factors may play an important role in the racial disparities in the risk of prostate and testicular cancers.

It has been observed that men of African ancestry have a higher incidence of prostate cancer and lower incidence of testicular cancer compared to men of European ancestry. However, little is known about underlying mechanisms accounting for these observations. The current study compares frequencies of all genetic alterations associated with risks of prostate cancer or testicular cancer between the two racial groups. Our findings suggest that differences in the frequencies of genetic alterations between the groups may help to explain the racial disparities in the risk of prostate and testicular cancers.

Fish intake and risk of melanoma in the NIH-AARP diet and health study.

PURPOSE: Prior epidemiological studies evaluating the association between fish intake and melanoma risk have been few and inconsistent. Few studies distinguished different types of fish intake with risk of melanoma. METHODS: We examined the associations between intake of total fish and specific types of fish and risk of melanoma among 491,367 participants in the NIH-AARP Diet and Health Study. We used multivariable-adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 6,611,941 person-years of follow-up with a median of 15.5 years, 5,034 cases of malignant melanoma and 3,284 cases of melanoma in situ were identified. There was a positive association between higher total fish intake and risk of malignant melanoma (HR = 1.22, 95% CI = 1.11-1.34 for top vs. bottom quintiles, ptrend = 0.001) and melanoma in situ (HR = 1.28, CI = 1.13-1.44 for top vs. bottom quintiles, ptrend = 0.002). The positive associations were consistent across several demographic and lifestyle factors. There were also positive associations between tuna intake and non-fried fish intake, and risk of malignant melanoma and melanoma in situ. However, fried fish intake was inversely associated with risk of malignant melanoma, but not melanoma in situ. CONCLUSIONS: We found that higher total fish intake, tuna intake, and non-fried fish intake were positively associated with risk of both malignant melanoma and melanoma in situ. Future studies are needed to investigate the potential biological mechanisms underlying these associations.

Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk.

BACKGROUND: Testicular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation. METHODS: In this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls. RESULTS: In individual SNP analyses, seven SNPs, four mapping within MTHFR, were associated with TGCT risk after correction for multiple testing (q ≤ 0.05). Queries of public databases showed that three of these SNPs were associated with MTHFR changes in enzymatic activity (rs1801133) or expression level in testis tissue (rs12121543, rs1476413). Gene-based analyses revealed MTHFR (q = 8.4 × 10-4), methyl-CpG-binding protein 2 (MECP2; q = 2 × 10-3), and ZBTB4 (q = 0.03) as the top TGCT-associated genes. Stratifying by tumor histology, four MTHFR SNPs were associated with seminoma. In gene-based analysis MTHFR was associated with risk of seminoma (q = 2.8 × 10-4), but not with nonseminomatous tumors (q = 0.22). CONCLUSIONS: Genetic variants within MTHFR, potentially having an impact on the DNA methylation pattern, are associated with TGCT risk. IMPACT: This finding suggests that TGCT pathogenesis could be associated with the folate cycle status, and this relation could be partly due to hereditary factors.

B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS.

BACKGROUND: A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non-Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes. METHODS: In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell-mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression. RESULTS: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08-1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59-2.07; P-trend (Ptrend) < 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell-mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction. CONCLUSIONS: Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions. IMPACT: Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL.

Identification of 22 susceptibility loci associated with testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.

Dataset of testicular germ cell tumors (TGCT) risk associated with serum polychlorinated biphenyl (PCB) by age at diagnosis and histologic types.

In a population-based case control study of testicular germ cell tumors (TGCT), we reported a strong positive association between serum levels of Wolff's Group 1 (potentially estrogenic) polychlorinated biphenyl (PCBs) and risk of TGCT, and the observed associations were similar for both seminoma and non-seminoma. While the observed specific associations between TGCT and Wolff's Group 1 PCBs cannot be easily explained by bias or confounding, a question can still be asked, that is, could the relationship between PCBs and TGCT differ by age at diagnosis? PCBs tend to bioaccumulate, with more heavily chlorinated PCB congeners tending to have longer half-lives. Half-lives of PCB congeners were reported ranging from 4.6 years for PCB-28 to 41.0 years for PCB-156. The half-life for the heavy PCB congeners (17.8 years) was found to be approximately twice that for the light PCBs (9.6 years) in early studies. Therefore, the same PCB concentration measured in a 20-year-old vs. a 55-year-old is unlikely to represent the same lifetime PCB exposure or type of PCB exposure. In this analysis, we stratified the data by median age of diagnosis of TGCT and further stratified by histologic type of TGCT (seminoma vs non-seminoma) to explore if the risk of TGCT associated with PCB exposures differs by age.

Serum polychlorinated biphenyl (PCB) levels and risk of testicular germ cell tumors: A population-based case-control study in Connecticut and Massachusetts.

The incidence rate of testicular germ cell tumors (TGCT) has continuously increased in Western countries over the last several decades. Some epidemiologic studies have reported that the endocrine disrupting polychlorinated biphenyls (PCBs) in serum may be associated with TGCT risk, but the evidence is inconsistent. Our goal was to investigate whether serum levels of PCBs are associated with the increase of TGCT risk. We conducted a population-based case-control study of 308 TGCT cases and 323 controls, all residents of Connecticut and Massachusetts. Serum levels of 56 PCBs congeners were measured using gas chromatography and unconditional logistic regression model was used to evaluate the risk of TGCT associated with total PCBs exposure, groups of PCBs categorized by Wolff's functional groups, and individual PCB congeners. The results showed that there was no association between total serum levels of PCBs and risk of TGCT overall (quartile 4 (Q4) vs. quartile 1 (Q1) odds ratio (OR) and 95% confidence interval (C.I.) = 1.0 (0.6-1.9), ρ trend = 0.9). However, strong positive association was observed between total serum levels of Wolff's Group 1 (potentially estrogenic) PCBs and risk of overall TGCT (Q4 vs. Q1 OR = 2.5, 95% CI = 1.3-4.7, ρ trend <0.05) as well as seminoma and non-seminoma subtypes. Wolff's Group 1 PCB congeners that showed an increased risk of TGCT included: 25, 44, 49, 52, 70, 101, 174, and 201/177. Considering the continuing increase of TGCT, these associations should be replicated in different populations with larger sample size.

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

Urinary biomarkers of phthalates exposure and risks of thyroid cancer and benign nodule.

Phthalates have been reported to affect the function and growth of thyroid. However, there is little data on the effect of phthalates on thyroid oncogenesis. Here we explored the associations between phthalates exposure and the risks of thyroid cancer and benign nodule. We sex-matched 144 thyroid cancer, 138 benign nodule patients and 144 healthy adults from Wuhan, China. Eight phthalate metabolites in spot urine samples were quantified using high-performance liquid chromatography and tandem mass spectrometry. The associations of creatinine-corrected urinary phthalate metabolites with the risks of thyroid cancer and benign nodule were assessed using multivariable logistic regression models. We found that urinary monomethyl phthalate (MMP), mono(2-ethyl-5hydroxyhexyl) phthalate (MEHHP) and mono(2-ethylhexyl) phthalate (MEHP) associated with increased risks of thyroid cancer and nodule, with adjusted odds ratios (ORs) ranging from 1.74 to 4.78 comparing the extreme tertiles, and urinary monobutyl phthalate (MBP) was associated with decreased risks of thyroid cancer and benign nodule (all P for trends < 0.05). Male-specific positive associations of urinary monoethyl phthalate (MEP) with thyroid cancer and nodule as well as urinary mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) with thyroid cancer were also observed. Our results suggest that exposure to certain phthalates may contribute to increased risks of thyroid cancer and benign nodule.

Effects of hepatitis B virus infection, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase on prediabetes and diabetes mellitus: A cohort study.

INTRODUCTION AND OBJECTIVES: The purpose of this study was to confirm whether hepatitis B virus (HBV) infection and the levels of liver enzymes would increase the risk of prediabetes and diabetes mellitus (DM) in China. MATERIALS AND METHODS: A total of 10,741 individuals was enrolled in this prospective cohort study. Cox regression analysis was used to calculate the Hazard ratios (HRs) to evaluate the relationships between HBV infection and the risk of DM and prediabetes. Decision trees and dose response analysis were used to explore the effects of liver enzymes levels on DM and prediabetes. RESULTS: In baseline population, HBV infection ratio was 5.31%. In non-adjustment model, the HR of DM in HBV infection group was 1.312 (95% CI, 0.529-3.254). In model adjusted for gender, age and liver cirrhosis, the HR of DM in HBV infection group were 1.188 (95% CI, 0.478-2.951). In model adjusted for gender, age, liver cirrhosis, smoking, drinking, the HR of DM was 1.178 (95% CI, 0.473-2.934). In model further adjusted for education, family income and occupation, the HR of DM was 1.230 (95% CI, 0.493-3.067). With the increases of levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma-glutamyl transferase (GGT), the risk of prediabetes was gradually increasing (Pnon-linearity<0.05). There were dose-response relationships between ALT, GGT and the risk of DM (Pnon-linearity<0.05). CONCLUSIONS: HBV infection was not associated with the risk of prediabetes and DM. The levels of liver enzymes increased the risk of prediabetes and DM.

Prenatal and postnatal cadmium exposure and cellular immune responses among pre-school children.

BACKGROUND: Experimental studies have demonstrated that cadmium exposure induces alterations on immune function, but epidemiological evidence is lacking. OBJECTIVE: To examine the associations between prenatal and postnatal cadmium exposure and cellular immune responses among pre-school children. METHODS: Pre-school aged children (n = 407) were followed from a prospective birth cohort study in Wuhan, China. Maternal urinary and children's plasma cadmium concentrations were measured as biomarkers of prenatal and postnatal cadmium exposure, respectively. Children's cellular immune responses were assessed by peripheral blood T lymphocyte subsets and plasma cytokines. Multivariable adjusted models were applied to estimate the associations of prenatal and postnatal cadmium exposure with T lymphocyte subsets and cytokines, and the effect modification by child gender were also examined. RESULTS: Maternal urinary cadmium was associated with reduced absolute counts of CD3+CD4+ cells (-12.45%; 95% CI: -23.74%, 0.40% for the highest vs. lowest quartile; p for trend = 0.045). Inverse associations of maternal urinary cadmium with %CD3+CD4+ cells and CD4+/CD8+ ratio were only observed among females (both p-interaction < 0.050); whereas an inverse association with absolute counts of CD3+CD8+ cells was only observed among males (p-interaction = 0.057). Positive associations of maternal urinary cadmium with %CD3+CD4+ cells, interleukin-4 (IL-4), and IL-6 were only observed among females, although there were no significant interactions. We observed no clear associations of children's plasma cadmium with T lymphocyte subsets and cytokines. CONCLUSION: Prenatal but not postnatal cadmium exposure was associated with sex-specific alterations on children's cellular immune responses.

Occupational exposure to heavy metals, alcohol intake, and risk of type 2 diabetes and prediabetes among Chinese male workers.

OBJECTIVE: Both exposure to heavy metals and alcohol intake have been related to the risk of type 2 diabetes (T2D). In this study, we aimed to assess the potential interactions between metal exposure and alcohol intake on the risk of T2D and prediabetes in a cohort of Chinese male workers. METHODS: We conducted a cross-sectional analysis of 26,008 Chinese male workers in an occupational cohort study from 2011 to 2013. We assessed metal exposure and alcohol consumption at baseline in these workers who were aged ≥20 years. Based on occupations which were categorized according to measured urine metal levels, multiple logistic regression analyses were used to evaluate the independent and joint effects of metal and alcohol exposure on the risk of T2D and prediabetes. RESULTS: Risks of T2D (P trend = 0.001) and prediabetes (P trend = 0.001) were significantly elevated with increasing number of standard drinks per week, years of drinking, and lifetime alcohol consumption. An adjusted odds ratio (OR) of 6.1 (95% confidence interval [CI]: 4.8-7.8) was observed for the smelting/refining workers (highest metal exposure levels) who had the highest lifetime alcohol consumption (>873 kg) (P interaction = 0.018), whereas no statistically significant joint effect was found for prediabetes (P interaction = 0.515). CONCLUSIONS: Both exposures to metal and heavy alcohol intake were associated with the risk of diabetes in this large cohort of male workers. There was a strong interaction between these two exposures in affecting diabetes risk that needs to be confirmed in future studies.

The long-term rapid increase in incidence of adenocarcinoma of the kidney in the USA, especially among younger ages.

BACKGROUND: We previously observed a rapid increase in the incidence of renal cell carcinoma (RCC) in men and women between 1935 and 1989 in the USA, using data from the Connecticut Tumor Registry. This increase appeared to be largely explained by a positive cohort effect, but no population-based study has been conducted to comprehensively examine age-period-cohort effects by histologic types for the past decade. METHODS: We calculated age-adjusted and age-specific incidence rates of the two major kidney-cancer subtypes RCC and renal urothelial carcinoma, and conducted an age-period-cohort analysis of 114 138 incident cases of kidney cancer reported between 1992 and 2014 to the Surveillance, Epidemiology, and End Results programme. RESULTS: The age-adjusted incidence rates of RCC have been increasing consistently in the USA among both men and women (from 12.18/100 000 in 1992-1994 to 18.35/100 000 in 2010-2014 among men; from 5.77/100 000 in 1992-1994 to 8.63/100 000 in 2010-2014 among women). Incidence rates generally increased in successive birth cohorts, with a continuing increase in rates among the younger age groups (ages 0-54 years) in both men and women and among both Whites and Blacks. These observations were confirmed by age-period-cohort modelling, which suggested an increasing birth-cohort trend for RCC beginning with 1955 birth cohorts, regardless of the assumed value for the period effect for both men and women and for Whites and Blacks. CONCLUSIONS: Known risk factors for kidney cancer may not fully account for the observed increasing rates or the birth-cohort pattern for RCC, prompting the need for additional etiologic hypotheses (such as environmental exposures) to investigate these descriptive patterns.

Blood transfusion history and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis.

PURPOSE: To conduct a pooled analysis assessing the association of blood transfusion with risk of non-Hodgkin lymphoma (NHL). METHODS: We used harmonized data from 13 case-control studies (10,805 cases, 14,026 controls) in the InterLymph Consortium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusted for study design variables. RESULTS: Among non-Hispanic whites (NHW), history of any transfusion was inversely associated with NHL risk for men (OR 0.74; 95% CI 0.65-0.83) but not women (OR 0.92; 95% CI 0.83-1.03), pheterogeneity = 0.014. Transfusion history was not associated with risk in other racial/ethnic groups. There was no trend with the number of transfusions, time since first transfusion, age at first transfusion, or decade of first transfusion, and further adjustment for socioeconomic status, body mass index, smoking, alcohol use, and HCV seropositivity did not alter the results. Associations for NHW men were stronger in hospital-based (OR 0.56; 95% CI 0.45-0.70) but still apparent in population-based (OR 0.84; 95% CI 0.72-0.98) studies. CONCLUSIONS: In the setting of a literature reporting mainly null and some positive associations, and the lack of a clear methodologic explanation for our inverse association restricted to NHW men, the current body of evidence suggests that there is no association of blood transfusion with risk of NHL.

Interactions between serum folate and human papillomavirus with cervical intraepithelial neoplasia risk in a Chinese population-based study.

Background: Although folate deficiency has long been implicated in cancer development, uncertainties remain concerning its role in cervical cancer prevention. In particular, the interaction between human papillomavirus (HPV) and folate in the risk of cervical intraepithelial neoplasia (CIN) has been little studied. Objective: The goal of this study was to evaluate the dose-response association of serum folate with the risk of CIN, and the potential for HPV to modify the risk of CIN. Design: We performed a cross-sectional analysis of screening data in 2304 women aged 19-65 y who participated in an ongoing cohort of 40,000 women in China. Both categoric and spline analyses were used to evaluate the dose-response relation between serum folate and CIN risk. Results: After adjusting for potential confounders, a statistically significant inverse association between serum folate concentration and at least grade 2 CIN (CIN2+) risk was observed (1st quartile compared with 4th quartile: OR = 1.40; 95% CI: 1.09, 1.79; P-trend < 0.01); however, serum folate concentration was not associated with CIN1 risk. The risk patterns are similar when limited to only CIN2 and CIN3. An inverse linear relation between increased serum folate concentration and the risk of higher-grade CIN (CIN2, CIN3, and CIN2+) was also observed (for CIN2+: P-overall < 0.01, P-nonlinearity = 0.96). The highest risk of CIN2+ was observed in women with high-risk HPV types, who also had the lowest serum folate concentrations (P-interaction < 0.01). Conclusions: Our study indicates that serum folate is inversely associated with the risk of higher-grade CIN in Chinese women either with or without high-risk HPV infection. Thus, maintenance of normal serum folate levels may prove important for reducing the risk of CIN in women.

Maternal exposure to nickel in relation to preterm delivery.

Prior studies have suggested the reproductive effects of nickel; however, few epidemiological studies have investigated the associations of maternal exposure to nickel with preterm delivery. To investigate prenatal exposure to nickel as a risk factor for preterm delivery (< 37 weeks) in a large birth cohort. A total of 7291 pregnant women participated in the study were recruited between September 2012 and October 2014 in the longitudinal Healthy Baby Cohort (HBC) in Wuhan, China. Inductively Coupled Plasma Mass Spectrometry was employed to examine levels of nickel in urine from pregnant women collected before labor. The median urinary creatinine-corrected nickel was 5.05 creatinine µg/g with an inter-quartile range of 2.65-9.51 creatinine µg/g. We adjusted for potential confounders and found that each doubling in concentration of maternal urinary nickel was associated with an increase of 16% in adjusted odds ratios (ORs) for preterm delivery (95% CI: 1.08, 1.24). The associations were consistent for both spontaneous and iatrogenic preterm delivery. Our findings suggest that higher maternal urinary nickel concentrations were associated with an increased risk of preterm delivery.

HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes.

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.

A three year study of metal levels in skin biopsies of whales in the Gulf of Mexico after the Deepwater Horizon oil crisis.

In response to the explosion of the Deepwater Horizon and the massive release of oil that followed, we conducted three annual research voyages to investigate how the oil spill would impact the marine offshore environment. Most investigations into the ecological and toxicological impacts of the Deepwater Horizon Oil crisis have mainly focused on the fate of the oil and dispersants, but few have considered the release of metals into the environment. From studies of previous oil spills, other marine oil industries, and analyses of oil compositions, it is evident that metals are frequently encountered. Several metals have been reported in the MC252 oil from the Deepwater Horizon oil spill, including the nonessential metals aluminum, arsenic, chromium, nickel, and lead; genotoxic metals, such as these are able to damage DNA and can bioaccumulate in organisms resulting in persistent exposure. In the Gulf of Mexico, whales are the apex species; hence we collected skin biopsies from sperm whales (Physeter macrocephalus), short-finned pilot whales (Globicephala macrorhynchus), and Bryde's whales (Balaenoptera edeni). The results from our three-year study of monitoring metal levels in whale skin show (1) genotoxic metals at concentrations higher than global averages previously reported and (2) patterns for MC252-relevant metal concentrations decreasing with time from the oil spill.