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Kelly K Filipski, John D Murphy, Kathy J Helzlsouer Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA Abstract: Pharmacogenomics has identified important drug–gene interactions that affect the safety and efficacy of medications. Direct-to-consumer genetic testing, when first introduced, included some pharmacogenomic-related genes. The current landscape of pharmacogenomic direct-to-consumer testing is reviewed. Prior published reviews of the literature were updated through February 2017 and a scan of the current availability of direct-to-consumer genomic testing by companies was conducted. Results of the review demonstrate a shift toward physician-approved ordering. Keywords: pharmacogenomics, direct-to-consumer testing

Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50-<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers. [ABSTRACT FROM AUTHOR]

A nested case-control study, including 830 cases and 992 controls from 7 cohorts, was conducted to evaluate the association of circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, with risk of endometrial cancer. Matching factors included age at blood donation, date of blood donation, and race. Conditional logistic regression was used in the main analysis. The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L) (P = 0.08). However, there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index. Compared with the 50-<75 nmol/L 25(OH)D category, the body mass index-adjusted odds ratios and 95% confidence intervals were 1.08 (95% confidence interval: 0.73, 1.57) for the <25 nmol/L category and 0.90 (95% confidence interval: 0.51, 1.58) for the > or =100 nmol/L category (P(trend) = 0.99). Similarly null results were observed after further adjustment for other known risk factors and in stratified analyses. Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out (the highest category of 25(OH)D was > or =100 nmol/L, and for stratified analyses, > or =75 nmol/L), these results do not support a protective role of vitamin D against endometrial cancer. [ABSTRACT FROM AUTHOR]

Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of > or =75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically. [ABSTRACT FROM AUTHOR]

Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. [ABSTRACT FROM AUTHOR]

Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (P(trend) = 0.68) or by sex (men, P(trend) = 0.50; women, P(trend) = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects. [ABSTRACT FROM AUTHOR]

Background: Nicotine replacement therapy (NRT) has been shown to assist smokers to stop smoking in randomized trials, but little is known about its use in the general population. Methods: As part of ongoing follow-up of a cohort established in 1989 in Washington County, Maryland, a questionnaire mailed in 1998 included a question about ever use of the two NRT products then available over-the-counter: nicotine gum and nicotine patch. This study reports on ever use of NRT among the 1,954 respondents who were current smokers in 1989 and subsequently provided data on NRT use and smoking habits in 1998. Results: Overall, 36% of the smokers in 1989 had ever used NRT in some form by 1998; 10% used gum only, 16% used patch only, and 10% used both gum and patch. Number of cigarettes smoked per day at baseline was the strongest predictor of ever use of NRT (ptrend < 0.001). Compared to nonusers, ever users of NRT were more likely to have more than 12 years of education (p < 0.01) and be 25-54 years old at baseline (p < 0.001). When NRT use was assessed in relation to smoking status in 1998, 30% of NRT ever users compared to 39% of nonusers had quit smoking (p < 0.01). Among persistent smokers, the likelihood of reducing the number of cigarettes smoked per day was similar between NRT ever users (40%) and nonusers (41%). Conclusions: Ever use of NRT was common among this cohort of smokers, particularly among heavy smokers. Compared to nonusers, ever users of NRT were less likely to have stopped smoking and equally likely to cut down the frequency of smoking. This may reflect a tendency to turn to NRT for help after failing to quit by other means. [ABSTRACT FROM AUTHOR]

More information is needed about the relative effectiveness of prophylactic surgery, chemoprevention, and surveillance in reducing breast and ovarian cancer risk in women with an inherited susceptibility mutation. We assessed practical and ethical barriers to conducting randomized clinical trials (RCTs) to compare preventive interventions for breast and ovarian cancer. Eighty-seven at-risk women who attended an education and counseling session about BRCA1/2 testing were asked about their willingness to participate in hypothetical research studies for breast and ovarian cancer risk reduction. In addition, 247 Maryland physicians from five specialties completed a mail survey including a question about their likelihood of recommending RCT participation to an at-risk woman. Nineteen percent of at-risk women reported willingness to participate in a hypothetical RCT for breast cancer risk reduction and 17% for ovarian cancer risk reduction. Women with children and women likely to have a prophylactic mastectomy if found to have a susceptibility mutation were significantly more willing to participate in an RCT. A majority of women would be willing to participate in nonrandomized trials or registries. Fifty-two percent of physicians responded that they would be likely to recommend RCT participation to a woman carrying a breast cancer susceptibility mutation. Oncologists were the most likely to recommend an RCT. Although the results of nonrandomized trials may be difficult to interpret because of such issues as selection bias. Greater feasibility combined with fewer ethical concerns make nonrandomized trials a more viable alternative to randomized trials for evaluation of preventive interventions for breast and ovarian cancer when prophylactic surgery is one of the treatments being evaluated. [ABSTRACT FROM AUTHOR]

Background: The legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis., Methods: A total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples., Results: Overall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use., Conclusion: This geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication., (Published by Oxford University Press 2024.)

Expanding legal access to medical cannabis across the United States increases availability and use of cannabis products to manage cancer-related symptoms and treatment side effects despite the lack of research-based evidence on its potential benefits and harms. To address knowledge gaps in how cancer patients access and use cannabis, their perceived risks and benefits with its use, and whether cancer patients discuss cannabis use with their healthcare providers during treatment, the National Cancer Institute (NCI) supported 12 NCI-designated comprehensive cancer centers to conduct surveys, which included NCI standardized core questions on cannabis use during treatment, among their cancer patient populations. This overview highlights key results from the articles contained in the monograph, which includes a summary of the results of core questions across all centers and reports from individual or groups of cancer centers on survey results related to the sourcing of cannabis, associated cost, behavioral factors associated with cannabis use (such as smoking, drinking, or using other substances), patient-provider communication on cannabis use during treatment, ethnic variations in patterns, sources, and reasons for cannabis use as well as methodologic concerns related to survey data analysis. The results of these surveys of cannabis use after the diagnosis of cancer lay the groundwork for much-needed research to answer the questions of benefits and harms, including potential interactions with cancer treatments for cancer patients., (Published by Oxford University Press 2024.)

Scientific research requires a substantial investment of time, effort, and money by researchers and funders. The funding that would be needed for all meritorious proposals far exceeds available resources. Major funding organizations use a multistep process for allocating research dollars that follows and extends beyond scientific peer review with considerations including mission priority, budget, and potential duplication of past or ongoing research activities. At the level of programmatic review, the process tends to be less proscribed than scientific review, but considerations relate to and are akin to basic value-driven economic principles. We propose a framework that encompasses the elements of programmatic review and provide examples of how the economic principles of opportunity costs, diminishing marginal productivity, sunk costs, economic optimization, return on investment, and option value apply to both research planning and funding decisions. Examples use cancer control population science research, as the nature of observational and interventional research involves large population studies (large sample size, recruitment, and often long-duration follow-up costs) which demand a high level of resource utilization; the same principles can be applied throughout medical and population health research. Awareness of the aspects of programmatic review and context to focus discussion regarding funding decisions may help guide research planning, decision-making, and increase transparency of the overall review process., (©2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression., Design: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression., Participants: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer., Methods: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study., Main Outcome Measures: Overall mortality and CM., Results: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration., Conclusions: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. All rights reserved.)

Purpose: Genetic testing is a tool used in a variety of settings for medical and nonhealth related purposes. The goal of this analysis was to better understand the awareness and use of genetic testing in the United States., Methods: Data from the 2020 Health Information National Trends Survey 5 cycle 4 were used to assess the awareness and use of genetic testing by demographic characteristics, personal cancer history, and family cancer history., Results: Overall, 75% of participants were aware of genetic testing and 19% of participants had genetic testing. Ancestry testing was the most common type of testing that the participants were aware of and had received. Non-Hispanic Asian, Non-Hispanic Black, and Hispanic respondents and participants with incomes less than $20,000 were less likely to be aware of and have received any type of genetic testing than the Non-Hispanic White participants and participants with higher income, respectively. Participants with a family history of cancer were more likely to be aware of cancer genetic testing than those without, and participants with a personal history of cancer were more likely to have had cancer genetic testing., Conclusion: It appears awareness of genetic testing is increasing in the United States, and differences in awareness persist by race/ethnicity and income., Competing Interests: Conflict of Interest All the authors are employed by the National Institutes of Health. The authors declare no conflict of interest., (Published by Elsevier Inc.)

Strategic planning is conducted by many organizations to systematically evaluate and assess their current state, establish or update their mission and/or goals, and identify strategies and activities to achieve the goals. The National Cancer Institute (NCI) Cohort Consortium is a collaborative network of 62 prospective cohort studies and their affiliated investigators that focus on cancer etiology and outcome research. The organization's membership grew markedly from 10 cohort studies at its inception in 2001 to 59 cohort studies at the time of the launch of the Consortium's strategic planning in 2017. This paper describes the strategic planning process that was conducted to establish organizational goals and to develop strategies and activities consistent with the Consortium's mission. The process involved a 2-year iterative approach combining surveys and in-person meetings. The resulting goals focus on communication, career development, research facilitation, scientific gaps, and common scientific challenges. The NCI Cohort Consortium's strategic plan and evaluation of its progress will advance new initiatives in cancer etiology and survivorship research., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome., Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data., Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex., Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk., Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer., (©2020 American Association for Cancer Research.)