SUMMARY Testicular germ cell tumors (TGCT), which comprise 98% of all testicular malignancies, are the most commonly occurring cancers among men between the ages of 15 and 44 years in the United States (U.S.). A prior report from our group found that while TGCT incidence among all U.S. men increased between 1973 and 2003, the rate of increase among black men was more pronounced starting in 1989–1993 than was the rate of increase among other men. In addition, TGCT incidence increased among Hispanic white men between 1992 and 2003. To determine whether these patterns have continued, in the current study we examined temporal trends in incidence through 2011. Between 1992 and 2011, 21,271 TGCTs (12,419 seminomas; 8,715 nonseminomas; 137 spermatocytic seminomas) were diagnosed among residents of the Surveillance, Epidemiology, and End Results (SEER) 13 registry areas. The incidence of TGCT was highest among non-Hispanic white men (6.97 per 100,000 man-years) followed by American Indian/Alaska Native (4.66), Hispanic white (4.11), Asian/Pacific Islander (1.95), and black (1.20) men. Non-Hispanic white men were more likely to present with smaller tumors (3.5 cm) and localized disease (72.6%) than were men of other races/ethnicities. Between 1992 and 2011, TGCT incidence increased significantly among Hispanic white (APC: 2.94, p<0.0001), black (APC: 1.67, p=0.03), non-Hispanic white (APC: 1.23, p<0.0001), and Asian/Pacific Islander (APC: 1.04, p=0.05) men. Incidence rates also increased, although not significantly, among American Indian/Alaska Native men (APC: 2.96, p=0.06). The increases were greater for nonseminoma than seminoma. In summary, while non-Hispanic white men in the U.S. continue to have the highest incidence of TGCT, they present at more favorable stages of disease and with smaller tumors than do other men. The increasing rates among non-white men, in conjunction with the larger proportion of non-localized stage disease, suggest an area where future research is warranted.

Background Testicular germ cell tumors (TGCT) are rare tumors in the general population but are the most commonly occurring malignancy among men between ages 15 and 44 years in the United States (US). While non-Hispanic whites (NHW) have the highest incidence in the US, rates among Hispanics have shown the greatest increase in recent years. To forecast what these incidence rates may be in the future, an analysis of TGCT incidence in the Surveillance, Epidemiology, and End Results Program, and National Program of Cancer Registries was conducted. Methods TGCT incidence data among 15–59 year olds for the years 1999–2012 were obtained from 39 US cancer registries. Incidence rates through 2026 were forecast using age-period-cohort models, stratifying by race/ethnicity, histology (seminoma, nonseminoma), and age. Results Between 1999 and 2012, TGCT incidence rates, overall and by histology, were highest among NHWs, followed by Hispanics, Asian/Pacific Islanders, and non-Hispanic blacks. Between 2013 and 2026, rates among Hispanics were forecast to increase by 3.96% (95% Confidence Interval: 3.88–4.03) annually, the highest rate of increase of any racial/ethnic group. By 2026, the highest TGCT rates in the US will be among Hispanics, due to increases in both seminoma and nonseminoma. Rates among NHWs will increase slightly, while rates among other groups will decrease slightly. Conclusion By 2026, Hispanics will have the highest rate of TGCT of any racial/ethnic group in the US due to the rising incidence among recent birth cohorts. Reasons for the increase in younger Hispanics merit further exploration.

Background Risk of cancer is determined by a complex interplay of genetic and environmental factors. Although the study of gene-environment (GxE) interactions has been an active area of research, little is reported about the known findings in the literature. Methods To examine the state of the science in GxE research in cancer, we performed a systematic review of published literature using gene-environment or pharmacogenomic flags from two curated databases of genetic association studies, the Human Genome Epidemiology (HuGE) literature finder and Cancer Genome-Wide Association and Meta Analyses Database (CancerGAMAdb), from January 1, 2001, to January 31, 2011. A supplemental search using HuGE was conducted for articles published February 1, 2011, to April 11, 2013. A 25% sample of the supplemental publications was reviewed. Results A total of 3,019 articles were identified in the original search. From these articles, 243 articles were determined to be relevant based on inclusion criteria (more than 3,500 interactions). From the supplemental search (1,400 articles identified), 29 additional relevant articles (1,370 interactions) were included. The majority of publications in both searches examined GxE in colon, rectal, or colorectal cancer types; breast; or lung cancer. Specific interactions examined most frequently included environmental factors categorized as energy balance (e.g., body mass index (BMI), diet), exogenous (e.g., oral contraceptives) and endogenous hormones (e.g., menopausal status), chemical environment (e.g., grilled meats), and lifestyle (e.g., smoking, alcohol intake). In both searches, the majority of interactions examined were using loci from candidate genes studies and none of the studies were genome-wide interaction studies (GEWIS). The most commonly reported measure was the interaction p-value, of which a sizable number of p-values were considered statistically significant (i.e., < 0.05). In addition, the magnitudes of interactions reported were modest. Conclusion Observations of published literature suggest that opportunity exists for increased sample size in GxE research, including GWAS identified loci in GxE studies, exploring more GWAS approaches in GxE such as GEWIS, and improving the reporting of GxE findings.

Background Bisphenol A (BPA) is an environmental estrogen used in the manufacture of polycarbonate plastics and epoxy resins used to make food and beverage packaging. Increasing evidence suggests that BPA mimics estrogens in the body and may be associated with putative markers of breast cancer risk. Objectives We analyzed the National Health and Nutrition Examination Survey (NHANES) 2003–2010 data to investigate the association of BPA with age at menarche in adolescent girls. We hypothesized that urinary BPA, as a surrogate biomarker for BPA exposure, is associated with earlier age at menarche, and that body mass index (BMI) may modulate this association. Methods We conducted cross-sectional analyses of urinary BPA, BMI and age of menarche in a subsample of 987 adolescent girls aged 12–19, using pooled data from the 2003–2010 NHANES. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between urinary BPA and early onset of menarche, with adjustment for sampling design. We additionally assessed interaction of BPA with BMI. Results Adolescent girls with moderate BPA levels appeared to be less likely to have early onset of menarche than those with the lowest levels (OR=0.57; 95% CI=0.30, 1.08) after adjusting for age, race/ethnicity, parental education, country of birth, NHANES cycle, BMI and creatinine. BMI appeared to modify the BPA-menarche association. Conclusions Although a non-significant trend suggests increasing urinary BPA may be associated with delayed menarche in adolescent girls, these results are based on cross-sectional data. Results should be clarified in carefully designed longitudinal cohort studies.

Background: Indoor air pollution (IAP) derived largely from the use of solid fuels for cooking and heating affects about 3 billion people worldwide, resulting in substantial adverse health outcomes, including cancer. Women and children from developing countries are the most exposed populations. A workshop was held in Arlington, Virginia, 9–11 May 2011, to better understand women’s and children’s potential health effects from IAP in developing countries. Workshop participants included international scientists, manufacturers, policy and regulatory officials, community leaders, and advocates who held extensive discussions to help identify future research needs.Objectives: Our objective was to identify research opportunities regarding IAP and cancer, including research questions that could be incorporated into studies of interventions to reduce IAP exposure. In this commentary, we describe the state of the science in understanding IAP and its associations with cancer and suggest research opportunities for improving our understanding of the issues.Discussion: Opportunities for research on IAP and cancer include studies of the effect of IAP on cancers other than lung cancer; studies of genetic factors that modify susceptibility; studies to determine whether the effects of IAP are mediated via germline, somatic, and/or epigenetic changes; and studies of the effects of IAP exposure via dermal and/or oral routes.Conclusions: IAP from indoor coal use increases the risk of lung cancer. Installing chimneys can reduce risk, and some genotypes, including GSTM1-null, can increase risk. Additional research is needed regarding the effects of IAP on other cancers and the effects of different types of solid fuels, oral and dermal routes of IAP exposure, genetic and epigenetic mechanisms, and genetic susceptibility.

Background The incidence of testicular germ cell tumors (TGCT) in the United States (US) is notably higher among white men than other men. Previously, however, our group reported that rates were rising among Hispanics in certain areas. To determine whether this finding was evident in a wider area of the US, data from 39 US cancer registries were examined. Methods Racial/ethnic-specific incidence rates per 100,000 man-years were calculated overall and by census region for the period 1998–2011. Annual percent changes (APCs) were estimated and joinpoint models were fit. Differences in incidence by region were examined using the Wald test. Results During the time period 1998–2011, 88,993 TGCTs were recorded. TGCT incidence was highest among non-Hispanic whites (NHWs) (6.57/100,000), followed by Hispanics (3.88), American Indian/Alaska Natives (2.88), Asian/Pacific Islanders (A/PIs) (1.60), and non-Hispanic blacks (NHBs) (1.20). Incidence significantly increased among Hispanics (APC: 2.31, p<0.0001), with rates rising in all regions except the South. Rates rose slightly among NHWs (APC: 0.51, p=0.0076). Significant differences in rates by region were seen for Hispanics (p=0.0001), NHWs (p<0.0001) and A/PIs (p<0.0001) with the highest rates among Hispanics in the West, and highest rates among NHWs and A/PIs in the Northeast. Conclusions While TGCT incidence remained highest among NHWs between 1998 and 2011, the greatest increase was experienced by Hispanics. Rising rates of TGCT among Hispanics in the US suggest that future attention is warranted. Reasons for the increase may include variability in birthplace, changing exposures, genetic susceptibility, and/or length of US residence.

Meaningful engagement of Alaska Native (AN) tribes and tribal health organizations is essential in the conduct of socially responsible and ethical research. As genomics becomes increasingly important to advancements in medicine, there is a risk that populations not meaningfully included in genomic research will not benefit from the outcomes of that research. AN people have historically been underrepresented in biomedical research; AN underrepresentation in genomics research is compounded by mistrust based on past abuses, concerns about privacy and data ownership, and cultural considerations specific to this type of research. Working together, the National Human Genome Research Institute and two Alaska Native health organizations, Southcentral Foundation and the Alaska Native Health Board, cosponsored a workshop in July 2018 to engage key stakeholders in discussion, strengthen relationships, and facilitate partnership and consideration of participation of AN people in community-driven biomedical and genomic research. AN priorities related to translation of genomics research to health and health care, return of genomic results, design of research studies, and data sharing were discussed. This report summarizes the perspectives that emerged from the dialogue and offers considerations for effective and socially responsible genomic research partnerships with AN communities.

Given the distinct time-trends and age-specific patterns of testicular cancer in men aged ≥50 years, additional investigation of risk factors for these tumors is warranted.