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1.  High Prevalence of Screen Detected Prostate Cancer in West Africans: Implications for Racial Disparity of Prostate Cancer 
The Journal of urology  2014;192(3):730-735.
To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana.
Materials and Methods
We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies.
Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml.
In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology.
PMCID: PMC4332806  PMID: 24747091
prostatic neoplasms; prostate-specific antigen; mass screening; African Americans; Africa
2.  Dietary Cadmium Exposure and Risk of Breast, Endometrial, and Ovarian Cancer in the Women’s Health Initiative 
Environmental Health Perspectives  2014;122(6):594-600.
Background: In vitro and animal data suggest that cadmium, a heavy metal that contaminates some foods and tobacco plants, is an estrogenic endocrine disruptor. Elevated estrogen exposure is associated with breast, endometrial, and ovarian cancer risk.
Objectives: We examined the association between dietary cadmium intake and risk of these cancers in the large, well-characterized Women’s Health Initiative (WHI).
Methods: A total of 155,069 postmenopausal women, 50–79 years of age, who were enrolled in the WHI clinical trials or observational study, participated in this study. We estimated dietary cadmium consumption by combining baseline food frequency questionnaire responses with U.S. Food and Drug Administration data on food cadmium content. Participants reported incident invasive breast, endometrial, or ovarian cancer, and WHI centrally adjudicated all cases through August 2009. We applied Cox regression to estimate adjusted hazard ratios (HRs) and 95% CIs for each cancer, comparing quintiles of energy-adjusted dietary cadmium intake.
Results: Over an average of 10.5 years, 6,658 invasive breast cancers, 1,198 endometrial cancers, and 735 ovarian cancers were reported. We observed no statistically significant associations between dietary cadmium and risk of any of these cancers after adjustment for potential confounders including total dietary energy intake. Results did not differ in any subgroup of women examined.
Conclusions: We found little evidence that dietary cadmium is a risk factor for breast, endometrial, or ovarian cancers in postmenopausal women. Misclassification in dietary cadmium assessment may have attenuated observed associations.
Citation: Adams SV, Quraishi SM, Shafer MM, Passarelli MN, Freney EP, Chlebowski RT, Luo J, Meliker JR, Mu L, Neuhouser ML, Newcomb PA. 2014. Dietary cadmium exposure and risk of breast, endometrial, and ovarian cancer in the Women’s Health Initiative. Environ Health Perspect 122:594–600;
PMCID: PMC4050510  PMID: 24633137
3.  Sex disparities in cancer incidence by time period and age 
Cancer epidemiology manuscripts often point out that cancer rates tend to be higher among males than females, yet rarely is this theme the subject of investigation.
We used the Surveillance, Epidemiology, and End Results (SEER) program data to compute age-adjusted (2000 US standard population) sex-specific incidence rates and male-to-female incidence rate ratios (IRR) for specific cancer sites and histologies for the period 1975-2004.
The ten cancers with the largest male-to-female IRR were Kaposi sarcoma (28.73), lip (7.16), larynx (5.17), mesothelioma (4.88), hypopharynx (4.13), urinary bladder (3.92), esophagus (3.49), tonsil (3.07), oropharynx (3.06) and other urinary organs (2.92). Only five cancers had a higher incidence in females compared to males: breast (0.01), peritoneum, omentum and mesentery (0.18), thyroid (0.39), gallbladder (0.57), and anus, anal canal and anorectum (0.81). Between 1975 and 2004, the largest consistent increases in male-to-female IRR were for cancers of the tonsil, oropharynx, skin excluding basal and squamous, and esophagus, while the largest consistent decreases in IRR were for cancers of the lip and lung and bronchus. Male-to-female IRRs varied considerably by age, the largest increases of which were for ages 40-59 years for tonsil cancer and hepatocellular carcinoma. The largest decreases in male-to-female IRR by age, meanwhile, were for ages 30-49 years for thyroid cancer, ages ≥70 years for esophageal squamous cell carcinoma, and ages ≥30 years for lung and bronchus cancer.
These observations emphasize the importance of sex in cancer etiopathogenesis and may suggest novel avenues of investigation.
PMCID: PMC2793271  PMID: 19293308
Sex; Male; Female; SEER program; Neoplasms; Incidence; Epidemiology
4.  The association between inflammation-related genes and serum androgen levels in men: The Prostate, Lung, Colorectal, and Ovarian Study 
The Prostate  2011;72(1):65-71.
Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation-related genes.
In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation-related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5α-androstane-3α, 17β-diol glucuronide [3αdiol G], and 4-Androstene-3,17-dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome-wide scan. SNP-hormone associations were evaluated using linear regression of hormones adjusted for age. Gene-based p-values were generated using an adaptive rank truncated product method.
Suggestive associations were observed for two inflammation-related genes and circulating androgen levels (false discovery rate [FDR] q-value<0.1) in both SNP and gene-based tests. Specifically, T was associated with common variants in MMP2 and CD14, with the most significant SNPs being rs893226G>T in MMP2 and rs3822356T>C in CD14 (FDR q-value=0.09 for both SNPs). Other genes implicated in either SNP or gene-based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione.
These results suggest possible cross-talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk.
PMCID: PMC3156884  PMID: 21520164
Inflammation; Androgens; Genes; Testosterone; Polymorphism; Single Nucleotide
5.  Effect modification of endocrine disruptors and testicular germ cell tumor risk by hormone-metabolizing genes 
It has been hypothesized that the increased prevalence of testicular germ cell tumors (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the U.S. Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p′-DDE, chlordane-related compounds, and polychlorinated biphenyls (PCBs), modified by polymorphisms in 5 hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4, and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR=1.90, 95% CI, 1.01–3.56) compare to those with the lowest; there were no increased risk among men with the homozygous major allele genotype (p-interaction=0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45–55% reductions in TGCT risk for men with the highest quartiles compared to the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions<0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.
PMCID: PMC2891172  PMID: 19627379
polychlorinated biphenyls; persistent organochlorine pesticides; testicular germ cell tumors; hormone-metabolizing genes
6.  Prostate Cancer Incidence Rates in Africa 
Prostate Cancer  2011;2011:947870.
African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973–2007. Although population-based data in Africa are quite limited, the available data from IARC showed that rates among blacks were highest in the East (10.7–38.1 per 100,000 man-years, age-adjusted world standard) and lowest in the West (4.7–19.8). These rates were considerably lower than those of 80.0–195.3 observed among African Americans. Rates in Africa increased over time (1987–2002) and have been comparable to those for distant stage in African Americans. These patterns are likely due to differences between African and African American men in medical care access, screening, registry quality, genetic diversity, and Westernization. Incidence rates in Africa will likely continue to rise with improving economies and increasing Westernization, warranting the need for more high-quality population-based registration to monitor cancer incidence in Africa.
PMCID: PMC3200287  PMID: 22111004
7.  Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex-hormone binding globulin 
Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder.
To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphism (SNPs) in the 8q24 risk regions, spanning 128,101,433–128,828,043 bp, and serum androgen (testosterone, androstenedione, 3αdiol G, and bioavailable testosterone) and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55–74 years old) from a prospective cohort study, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log transformed biomarker levels.
Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P<1.1×10−3) and bioavailable testosterone (P<6.3×10−4). Suggestive associations were seen for a cluster of 9 SNPs in prostate cancer risk region 1 and androstenedione (P<0.05).
These preliminary findings require confirmation in larger studies, but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions may correlate with androgen levels.
These results may provide some clues for the strong link between 8q24 and prostate cancer risk.
PMCID: PMC2901401  PMID: 20551303
8q24; genetic polymorphisms; serum androgens
8.  Chronic typhoid infection and the risk of biliary tract cancer and stones in Shanghai, China 
Previous studies have shown a positive association between chronic typhoid carriage and biliary cancers. We compared serum Salmonella enterica serovar Typhi antibody titers between biliary tract cancer cases, biliary stone cases without evidence of cancer, and healthy subjects in a large population-based case-control study in Shanghai, China.
Participants included 627 newly diagnosed primary biliary tract cancer patients; 1,037 biliary stone cases (774 gallbladder and 263 bile-duct) and 959 healthy subjects without a history of cancer, randomly selected from the Shanghai Resident Registry.
Overall only 6/2,293 (0.26%) were Typhi positive. The prevalence of Typhi was 1/457 (0.22%), 4/977 (0.41%), and 1/859 (0.12%) among cancer cases, biliary-stone cases, and population controls, respectively.
We did not find an association between Typhi and biliary cancer in Shanghai, due to the very low prevalence of chronic carriers in this population.
The low seroprevalence of S. Typhi in Shanghai is unlikely to explain the high incidence of biliary cancers in this population.
PMCID: PMC3110129  PMID: 21535882
9.  International trends in the incidence of testicular cancer, 1973–2002 
While testicular cancer incidence rates have been widely reported in populations of Northern European ancestry, rates in other population have been less frequently examined. In a prior report, global testicular cancer incidence rates and trends for the years 1973–1997 were summarized. The current report extends these analyses with an additional 5 years of data from Cancer Incidence in Five Continents.
Age-standardized incidence rates over successive 5-year time periods were obtained for populations in the Americas, Asia, Europe, and Oceania.
In general, testicular cancer incidence remained highest in Northern European populations (8.0–9.0 per 100,000) and lowest in Asian and African populations (<1 per 100,000). One notable exception to this pattern, however, was the very high rate reported by the Valdivia, Chile registry (8.8 per 100,000). In many populations, incidence rates rose between 1973 and 2002, although the increases were strongest and most consistent among populations of European ancestry. In some European populations, such as those of Denmark and of Geneva, Switzerland, some plateauing of rates was evident in recent years. There was little evidence of increase and possible evidence of modest decline in rates in east Asian populations. In general, the trends by histology (seminoma, nonseminoma) were similar to one another.
Risk of testicular cancer remains high in Northern European populations and low in Asian and African populations. Reasons for increasing rates among Northern Europeans and more stable or declining rates among East Asians are unexplained, supporting the need for future etiologic studies.
PMCID: PMC2867073  PMID: 20447912
testicular cancer; trends; seminoma; nonseminoma
10.  Measuring Serum Melatonin in Epidemiologic Studies 
Epidemiologic data on serum melatonin, a marker of circadian rhythms, and cancer are sparse due largely to the lack of reliable assays with high sensitivity to detect relatively low melatonin levels in serum collected during daylight, as commonly available in most epidemiologic studies.
To help expand epidemiologic research on melatonin, we assessed the reproducibility and refined a currently available melatonin radioimmunoassay, and evaluated its application to epidemiologic investigations by characterizing melatonin levels in serum, urine, and/or plasma in 135 men from several ethnic groups.
Reproducibility was high for the standard 1.0 ml serum- (mean coefficient of variation (CV)=6.9%, intraclass correlation coefficient (ICC)=97.4%, n=2 serum pools in triplicate) and urine-based (mean CV=3.5%, ICC=99.9%) assays. Reproducibility for the 0.5 ml refined-serum assay was equally good (mean CV=6.6%%;ICC=99.0%). There was a positive correlation between morning serum melatonin and 6-sulfatoxymelatonin in 24-hour urine(r=0.46, P=0.008; n=49 subjects). Melatonin levels in serum-plasma pairs had a high correlation (r=0.97, P<1 × 10−4; n=20) Morning serum melatonin levels were five times higher than those from the afternoon (before 9 AM mean = 11.0 pg/mL versus after 11 AM mean=2.0 pg/mL). Chinese men had lower melatonin levels (mean=3.4 pg/mL), while Caucasian, African American, and Ghanaian men had similar levels (mean=6.7–8.6 pg/mL).
These results suggest that melatonin can be detected reliably in serum samples collected in epidemiologic studies in various racial groups.
With improved assays, it may be possible to investigate the role of melatonin and the emerging circadian rhythm hypothesis in cancer etiology in epidemiologic studies.
PMCID: PMC2856692  PMID: 20332275
melatonin; radioimmunoassay; assay variation; reproducibility
11.  Polychlorinated biphenyls and risk of testicular germ cell tumors 
Cancer research  2009;69(5):1901-1909.
Exposure to endocrine disrupting chemicals, such as polychlorinated biphenyls (PCBs), may alter hormonal balance and thereby, increase risk of testicular germ cell tumors (TGCT). To study the relationship of PCBs to TGCT, pre-diagnostic serum samples from 736 cases and 913 controls in the Servicemen’s Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Adjusted odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. PCB levels were examined in association with all TGCT and, separately, with each histologic type (seminoma, nonseminoma). Risks associated with seven functional groupings of PCBs, as well as sum of PCBs, were also examined. There were significantly decreased risks of TGCT in association with eight PCBs (PCB-118, PCB-138, PCB-153, PCB-156, PCB-163, PCB-170, PCB-180, PCB-187) and no association with the remaining three (PCB-99, PCB-101, PCB-183). The same eight congeners were significantly associated with decreased risk of nonseminoma, while five (PCB-138, PCB-153, PCB-156, PCB-163, PCB-170) were associated with decreased risk of seminoma. All functional groupings of PCBs were also associated with decreased risk of TGCT and of nonseminoma, while 3 of the 7 functional groups were associated with decreased risk of seminoma. Sum of PCBs was significantly associated with decreased risk of TGCT (ptrend=0.0008), nonseminoma (ptrend=0.001) and seminoma (ptrend=0.03). Overall, these data do not support the hypothesis that PCB exposure increases the risk of TGCT.
PMCID: PMC2794125  PMID: 19223531
polychlorinated biphenyls; testicular germ cell tumors; seminoma; nonseminoma

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