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author:("Zhou, lenke")
1.  Allergies, atopy, immune-related factors and childhood rhabdomyosarcoma: a report from the Children’s Oncology Group 
Rhabdomyosarcoma (RMS) is a highly malignant tumor of developing muscle that can occur anywhere in the body. Due to its rarity, relatively little is known about the epidemiology of RMS. Atopic disease is hypothesized to be protective against several malignancies; however, to our knowledge, there have been no assessments of atopy and childhood RMS. Therefore, we explored this association in a case-control study of 322 childhood RMS cases and 322 pair-matched controls. Cases were enrolled in a trial run by the Intergroup Rhabdomyosarcoma Study Group. Controls were matched to cases on race, sex, and age. The following atopic conditions were assessed: allergies, asthma, eczema, and hives; in addition we examined other immune-related factors: birth order, day-care attendance, and breastfeeding. Conditional logistic-regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for age, race, sex, household income, and parental education. As the two most common histologic types of RMS are embryonal (n=215) and alveolar (n=66), we evaluated effect heterogeneity of these exposures. Allergies (OR=0.60, 95% CI: 0.41–0.87), hives (OR=0.61, 95% CI: 0.38–0.97), day-care attendance (OR=0.48, 95% CI: 0.32–0.71), and breastfeeding for ≥12 months (OR=0.36, 95% CI: 0.18–0.70) were inversely associated with childhood RMS. These exposures did not display significant effect heterogeneity between histologic types (p>0.52 for all exposures). This is the first study indicating that atopic exposures may be protective against childhood RMS, suggesting additional studies are needed to evaluate the immune system’s role in the development of this tumor.
PMCID: PMC3869863  PMID: 23824786
Allergies; atopy; epidemiology; rhabdomyosarcoma; soft tissue sarcoma
2.  Genomic Copy Number Imbalances Associated with Bone and Non-bone Metastasis of Early-Stage Breast Cancer 
To identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis.
Patients and Methods
Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information about site of metastasis. The CoxBoost algorithm was used to select metastasis site-related CNIs and to fit a Cox proportional hazards model.
Gains at 1q41 and 1q42.12 and losses at 1p13.3, 8p22, and Xp11.3 were significantly associated with bone metastasis. Gains at 2p11.2, 3q21.3–22.2, 3q27.1, 10q23.1, and 14q13.2–3 and loss at 7q21.11 were associated with non-bone metastasis. To examine the joint effect of CNIs and clinical predictors, patients were stratified into three risk groups (low, intermediate, and high) based on the sum of predicted linear hazard ratios (HRs). For bone metastasis, the hazard (95% confidence interval) for the low-risk group was 0.32 (0.11–0.92) compared to the intermediate-risk group and 2.99 (1.74–5.11) for the high-risk group. For non-bone metastasis, the hazard for the low-risk group was 0.34 (0.17–0.66) and 2.33 (1.59–3.43) for the high-risk group. The prognostic value of loss at 8p22 for bone metastasis and gains at 10q23.1 for non-bone metastasis, and gain at 11q13.5 for both bone and non-bone metastases were externally validated in 335 breast tumors pooled from four independent cohorts.
Distinct CNIs are independently associated with bone and non-bone metastasis for early-stage breast cancer patients across cohorts. These data warrant consideration for tailoring surveillance and management of metastasis risk.
PMCID: PMC3993091  PMID: 24305980
Breast cancer; bone metastasis; non-bone metastasis; copy number imbalances; molecular inversion probe array
3.  Nativity disparities in late-stage diagnosis and cause-specific survival among Hispanic women with invasive cervical cancer: An analysis of Surveillance, Epidemiology, and End Results data 
Cancer causes & control : CCC  2013;24(11):1985-1994.
While cervical cancer screening and risk behaviors have been found to vary among U.S.- and foreign-born Hispanic women, many cancer epidemiology studies have conceptualized Hispanics as a homogenous group. Here we examine differences in cervical cancer stage at diagnosis and survival among Hispanic women by nativity.
We use data from the Surveillance, Epidemiology, and End Results (SEER) program, 1998–2008. Nativity was based on place of birth and was categorized as U.S.- versus foreign-born. Distant and regional tumors were classified as late-stage, while local tumors were classified as early-stage.
Forty seven percent of cases of invasive cervical cancer among Hispanics were diagnosed at a late stage and over half of invasive cervical cancer cases were among foreign-born women. Foreign-born Hispanic women were significantly more likely than U.S.-born Hispanics to have late-stage diagnosis, after adjusting for age at diagnosis and tumor histology (adjusted odds ration= 1.09, p-value = 0.003). There was heterogeneity in the association between nativity and survival by stage at diagnosis. Among cases with early-stage diagnosis, survival was poorer among foreign-born versus U.S.-born Hispanics after adjusting for age at diagnosis, histology, and cancer-directed therapy (adjusted HR = 1.31, p-value = 0.030). However, among cases with late-stage diagnosis, survival was better among foreign--born Hispanics (adjusted HR = 0.81, p-value < 0.001).
We hypothesize that nativity differences in survival may be indicative of diverse risk, screening, and treatment profiles. Given such differences, it may be inappropriate to aggregate Hispanics as a single group for cervical cancer research.
PMCID: PMC4115245  PMID: 23934001
Cervical cancer; Hispanic; SEER program; survival; stage at diagnosis; nativity
4.  Prognostic Value of Single Nucleotide Polymorphisms of Candidate Genes Associated with Inflammation in Early Stage Breast Cancer 
To examine the role of germline genetic variations in inflammatory pathways as modifiers of time to recurrence (TTR) in patients with early stage breast cancer (BC), DNA from 997 early stage BC patients was genotyped for 53 tagging single nucleotide polymorphisms (SNPs) in 12 genes involved in inflammation. SNPs were analyzed separately for Caucasians versus African Americans and Hispanics. Cox proportional hazards models were used to evaluate the association between SNPs in the inflammatory genes and time to recurrence (TTR), adjusted for clinical and pathologic covariates. In univariable analyses of Caucasian women, the homozygous genotype of 12 SNPs, including 6 NFKB1 SNPs, 4 IL4 SNPs, and 2 IL13 SNPs, were significantly associated with a decrease in TTR compared with the heterozygous and/ or corresponding homozygous genotype (P <0.05). The significant NFKB1 and IL4 SNPs were in an area of high linkage disequilibrium (D'>0.8). After adjusting for stage, age, and treatment, carriage of the homozygous genotypes for NFKB1rs230532 and IL13rs1800925 were independently associated with a shorter TTR (P=0.001 and p=0.034, respectively). In African-American and Hispanic patients, expression of NFKB1rs3774932, TNFrs1799964, and IL4rs3024543 SNPs were associated with a shorter TTR in univariable model. Only NFKB1 rs3774932 (P=0.02) and IL4Rrs3024543 (P=0.03) had independent prognostic value in the multivariable model These data support the existence of host genetic susceptibility as a component in recurrence risk mediated by pro-inflammatory and immune factors, and suggest the potential for drugs which modify immune responses and inflammatory genes to improve prognosis in early stage BC.
PMCID: PMC3746974  PMID: 23529385
gene polymorphisms; inflammation; breast cancer
5.  Gender differences in sociodemographic and behavioral influences of physical activity in Mexican-origin adolescents 
Understanding the factors that contribute to physical activity (PA) in Mexican-origin adolescents is essential to the design of effective efforts to enhance PA participation in this population.
Multivariable logistic regression was used to identify sociodemographic and behavioral correlates of self-reported PA in school and community settings in 1,154 Mexican-origin adolescents aged 12–17 years in Houston, TX.
The majority of adolescents were born in the US (74%), approximately half (51%) were overweight or obese, and nearly three-quarters (73%) watched more than 2 hours of weekday television. Similarities and differences by setting and gender were observed in the relationships between sociodemographic and behavioral characteristics and PA. In boys, parental education and attending physical education (PE) were positively associated with PA across multiple PA outcomes. Adolescent linguistic acculturation was inversely associated with participation in community sports, whereas parental linguistic acculturation was positively associated with PA at school. In girls, PA in school and community settings was inversely associated with TV viewing and positively associated with PE participation.
These findings highlight similarities and differences in correlates of PA among boys and girls, and point towards potential sources of opportunities as well as disparities for PA behaviors in Mexican-origin adolescents.
PMCID: PMC3250565  PMID: 21952224
Mexican American; acculturation; physical education
6.  Policy implications of early onset breast cancer among Mexican-origin women 
Cancer  2011;117(2):390-397.
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 2003–2006, $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 five preventive services in the U.S. An additional 3,700 lives could be saved if 90% of women ≥40 years were recently screened for breast cancer. We examined risk for breast cancer in a case-control population-based sample of Mexican-origin women in Harris County, TX (n=714), where rates of breast cancer mortality for Latina women have doubled since 1990. Half of breast cancer cases (n=119) were diagnosed before the age of 50. In a multivariable model, women with a family history of breast cancer (OR=4.3), born in Mexico and having high levels of language acculturation (OR=2.5), and without health insurance (OR=1.6) were found to have the highest risk of breast cancer. Because Mexican-origin women were found to be of high-risk for early onset pre-menopausal breast cancer, we recommend policies targeting screening, education and treatment to prevent increased disparities in mortality. The inclusion of community members and policymakers as partners in these endeavors would further safeguard against an increase in cancer health disparities, and aid in formulating a policy agenda congruent with scientifically-based, community-driven policy efforts addressing breast cancer screening, education and treatment in this vulnerable population.
PMCID: PMC3071526  PMID: 21319396
7.  Risk analysis of severe myelotoxicity with temozolomide: The effects of clinical and genetic factors 
Neuro-Oncology  2009;11(6):825-832.
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) ≥ 2 m2 (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 ≥ 1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm3 (OR = 2.438, p = 0.03), BSA < 2 m2 (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 (O6-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.
PMCID: PMC2802402  PMID: 19179423
brain tumors; chemotherapy; myelotoxicity

Results 1-7 (7)