Renke Zhou

Risk analysis of severe myelotoxicity with temozolomide: The effects of clinical and genetic factors

A benefit of temozolomide (TMZ) is that myelotoxicity is uncommon. Recently, several small series have reported significant myelotoxicity resulting in treatment delays or death. The ability to predict risk of myelotoxicity may influence patient care. We retrospectively reviewed 680 malignant glioma patients and developed a clinical risk formula for myelotoxicity for each gender by logistic regression. The variables that remained were assigned a score of 1 and added together for a final risk score. Women experienced more myelotoxicity than did men (p = 0.015). For males, risk factors included body surface area (BSA) > or = 2 m(2) (odds ratio [OR] = 2.712, p = 0.04), not on steroids (OR = 2.214, p = 0.06), and on bowel medication (OR = 3.955, p = 0.008). For females, final factors included no prior chemotherapy (OR = 3.727, p = 0.001), creatinine > or = 1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm(3) (OR = 2.438, p = 0.03), BSA < 2 m(2) (OR = 4.178, p = 0.04), not on medication for gastroesophageal reflux disease (OR = 2.942, p = 0.01), and on analgesics (OR = 2.169, p = 0.05). Age was included because of observable trends. Risk of developing myelotoxicity ranged from 0% to 33% (male) and from 0% to 100% (females). Polymorphisms in NQO1 (NAD(P)H dehydrogenase, quinone 1), MGMT (O(6)-methylguanine-DNA methyltransferase), and GSTP1 (glutathione S-transferase pi 1) were related to risk of developing myelotoxicity in a subset of patients. Myelotoxicity with TMZ is a significant clinical issue for those at risk. Use of a clinical model to predict risk and evaluation of identified genetic polymorphisms related to myelotoxicity may allow for individualized dosing, optimizing patient management.

Policy implications of early onset breast cancer among Mexican-origin women

Overall, Latinas are more likely to be diagnosed with a more advanced stage of breast cancer and are 20% more likely to die of breast cancer than non‐Hispanic white women. It is estimated that from 2003 to 2006,

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study

82.0 billion in direct medical care expenditures, in addition to 100,000 lives annually, could be saved by eliminating health disparities experienced by Latinos and increasing the use of up to 5 preventive services in the United States. An additional 3700 lives could be saved if 90% of women aged ≥40 years were recently screened for breast cancer.

The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium

Background: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. Methods: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Results: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58–0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. Conclusion: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. Impact: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(2); 282–90. ©2016 AACR.

Copy Number Imbalances between Screen- and Symptom-Detected Breast Cancers and Impact on Disease-Free Survival

Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.

Genetic Modulation of Neurocognitive Function in Glioma Patients

Screening mammography results in the increased detection of indolent tumors. We hypothesized that screen- and symptom-detected tumors would show genotypic differences as copy number imbalances (CNI) that, in part, explain differences in the clinical behavior between screen- and symptom-detected breast tumors. We evaluated 850 women aged 40 and above diagnosed with stage I and II breast cancer at the University of Texas MD Anderson Cancer Center between 1985 and 2000 with information available on method of tumor detection (screen vs. symptoms). CNIs in screen- and symptom-detected tumors were identified using high-density molecular inversion probe arrays. Cox proportional modeling was used to estimate the effect of method of tumor detection on disease-free survival after adjusting for age, stage, and the CNIs. The majority of tumors were symptom detected (n = 603) compared with screen detected (n = 247). Copy number gains in chromosomes 2p, 3q, 8q, 11p, and 20q were associated with method of breast cancer detection (P < 0.00001). We estimated that 32% and 63% of the survival advantage of screen detection was accounted for by age, stage, nuclear grade, and Ki67 in women aged 50 to 70 and aged 40 to 87, respectively. In each age category, an additional 20% of the survival advantage was accounted for by CNIs associated with method of detection. Specific CNIs differ between screen- and symptom-detected tumors and explain part of the survival advantage associated with screen-detected tumors. Measurement of tumor genotype has the potential to improve discrimination between indolent and aggressive screen-detected tumors and aids patient and physician decision making about use of surgical and adjuvant treatments. Cancer Prev Res; 4(10); 1609–16. ©2011 AACR.

A pooled multisite analysis of the effects of atopic medical conditions in glioma risk in different ethnic groups

Purpose: Accumulating evidence supports the contention that genetic variation is associated with neurocognitive function in healthy individuals and increased risk for neurocognitive decline in a variety of patient populations, including cancer patients. However, this has rarely been studied in glioma patients. Experimental Design: To identify the effect of genetic variants on neurocognitive function, we examined the relationship between the genotype frequencies of 10,967 single-nucleotide polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase) and neurocognitive function in 233 newly diagnosed glioma patients before surgical resection. Four neuropsychologic tests that measured memory (Hopkins Verbal Learning Test—Revised), processing speed (Trail Making Test A), and executive function (Trail Making Test B, Controlled Oral Word Association) were examined. Results: Eighteen polymorphisms were associated with processing speed and 12 polymorphisms with executive function. For processing speed, the strongest signals were in IRS1 rs6725330 in the inflammation pathway (P = 2.5 × 10−10), ERCC4 rs1573638 in the DNA repair pathway (P = 3.4 × 10−7), and ABCC1 rs8187858 in metabolism pathway (P = 6.6 × 10−7). For executive function, the strongest associations were in NOS1 rs11611788 (P = 1.8 × 10−8) and IL16 rs1912124 (P = 6.0 × 10−7) in the inflammation pathway, and POLE rs5744761 (P = 6.0 × 10−7) in the DNA repair pathway. Joint effect analysis found significant gene polymorphism-dosage effects for processing speed (Ptrend = 9.4 × 10−16) and executive function (Ptrend = 6.6 × 10−15). Conclusions: Polymorphisms in inflammation, DNA repair, and metabolism pathways are associated with neurocognitive function in glioma patients and may affect clinical outcomes. Clin Cancer Res; 21(14); 3340–6. ©2015 AACR.

Uncovering nativity disparities in cancer patterns: Multiple imputation strategy to handle missing nativity data in the Surveillance, Epidemiology, and End Results data file

PURPOSE The incidences of atopic conditions (allergies, asthma, or eczema) and glioma vary by ethnicity. Atopic conditions are inversely associated with gliomas. We conducted a pooled multisite study investigating the associations of atopic conditions with glioma in different race/ethnicity groups. METHODS Using glioma cases and healthy controls, unconditional logistic regression was conducted to assess the associations of atopic conditions with glioma separately in white, black, Asian, and Hispanic subpopulations. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS Glioblastoma multiforme cases were less likely than controls to report a history of atopic conditions in whites (OR = 0.46, [95% CI, 0.38-0.54]) and Asians (OR = 0.27, [95% CI, 0.10-0.73]). The same trend was seen when looking at glioma cases of all histologies. An inverse association was not seen in blacks for glioblastoma multiforme or all histologies combined. CONCLUSIONS The inverse association between glioma and atopic conditions may vary by ethnicity due to a difference in the biology of atopic conditions in different ethnicities but may be due to chance because of the limitations of small nonwhite sample sizes.

History of chickenpox in glioma risk : a report from the glioma international case-control study (GICC)

Although birthplace data are routinely collected in the participating Surveillance, Epidemiology, and End Results (SEER) registries, such data are missing in a nonrandom manner for a large percentage of cases. This hinders analysis of nativity‐related cancer disparities. In the current study, the authors evaluated multiple imputation of nativity status among Hispanic patients diagnosed with cervical, prostate, and colorectal cancer and demonstrated the effect of multiple imputation on apparent nativity disparities in survival.

Allergies, atopy, immune-related factors and childhood rhabdomyosarcoma : a report from the Children's Oncology Group

Varicella zoster virus (VZV) is a neurotropic α‐herpesvirus that causes chickenpox and establishes life‐long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case‐Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two‐stage random‐effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65–0.96). Furthermore, the protective effect of chickenpox was stronger for high‐grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta‐analyses of the literature and investigations of the potential biological mechanism, are warranted.