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Biomedical subjects

Yutaka Yasui

Publications and source records attributed to Yutaka Yasui.

At least 37 records · Page 2Linked to original sources

Effect of exercise on bone mineral density and lean mass in postmenopausal women.

PURPOSE: To evaluate the effects of physical activity on bone mineral density, bone mineral content, and lean mass in postmenopausal, overweight/obese women. METHODS: We conducted a 12-month randomized controlled aerobic exercise intervention versus control in 173 sedentary, overweight/obese, postmenopausal women, aged 50-75 yr. The exercise prescription consisted of >or=45 min of moderate-intensity aerobic exercise (60-75% of maximal heart rate), 5 d.wk for 12 months. Control participants attended 45-min stretching sessions once a week. Ninety-eight percent (N=170) completed the trial. Exercisers averaged 172 min.wk (SD=89) of exercise and expended 3828 kJ.wk (SD=2053). We assessed body fat, total lean mass, and total body bone mineral density and content using dual-energy x-ray absortiometry (DXA). We compared baseline with 12-month changes in exercisers versus controls. RESULTS: Exercisers lost significantly more weight than stretchers (1.3-kg loss vs 0.1-kg gain, P=0.01). However, no differences between exercisers and controls in the change from baseline to 12 months were detected: exercisers' average bone mineral density increased by 0.005 g.cm and controls' by 0.003 g.cm (P=0.61). Similarly, no significant differences were detected for bone mineral content. Lean mass increased by 0.2 kg in both groups (P=0.84). CONCLUSION: Overall, the results from this randomized controlled study suggest that a yearlong moderate-intensity aerobic exercise intervention does not affect total body bone mineral density, bone mineral content, or lean mass in overweight/obese postmenopausal women.

Aged↗

Long-term outcomes of adult survivors of childhood cancer.

During the past 30 years, changes in the treatment of children and adolescents with cancer have led to substantial improvements in survival. Although treatment-related factors have been shown to impact subsequent health status and quality of life, there is limited information on survivors who are now two or more decades after treatment. The Childhood Cancer Survivor Study (CCSS) was established as a resource for investigating the long-term outcomes of a cohort of 5-year survivors of childhood and adolescent cancer, diagnosed between 1970-1986. The CCSS cohort has more than 14,000 active participants, including survivors of leukemia, brain tumors, Hodgkin disease, non-Hodgkin lymphoma, Wilms tumor, neuroblastoma, soft-tissue sarcoma, and bone tumors. Study participants, extensively characterized by their cancer therapy, have provided self-reported sociodemographic- and health-related information. Although the survivor population has been found to be at significantly increased risk of several adverse outcomes, such as late mortality, second cancers, pulmonary complications, pregnancy loss, low birth weight of offspring, and decreased education, the overall proportion of survivors affected is relatively small. Subgroups at high risk of adverse outcomes, defined by treatment-related, demographic, or medical factors, can be identified. The ongoing evaluation of large and diverse cohorts of cancer survivors will aid in further identifying individuals who should be the target of innovative intervention strategies.

Adolescent↗

Stroke as a late treatment effect of Hodgkin's Disease: a report from the Childhood Cancer Survivor Study.

PURPOSE: The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors. PATIENTS AND METHODS: The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings. RESULTS: Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% CI, 3.85 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% CI, 54.5 to 121.7 per 100,000 person-years). The RR of stroke among HD survivors was 4.32 (95% CI, 2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% CI, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P < .0001). CONCLUSION: Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease.

Adolescent↗

Long-term medical effects of childhood and adolescent rhabdomyosarcoma: a report from the childhood cancer survivor study.

BACKGROUND: This study was conducted to evaluate the incidence of adverse medical conditions and to assess the risk of developing these conditions in a cohort of long-term survivors of rhabdomyosarcoma (RMS) diagnosed before age 21. PROCEDURE: Using data from the Childhood Cancer Survivor Study (CCSS), we evaluated the incidence of self-reported adverse medical conditions for 606 RMS survivors and 3,701 siblings of cancer survivors. Cancer and treatment data abstracted from medical records were used to evaluate the effects of primary tumor site and combined modality therapy on the risk of developing sequelae in survivors. RESULTS: The relative risk (RR) for developing sequelae among survivors compared with siblings was greatest within 5 years after diagnosis. RR was elevated more than 5 years after diagnosis for several conditions (RR, 95% CI) as follows: eye impairment (cataract: 7.4, 2.9-18.9; visual disturbances: 3.2, 2.0-5.1; very dry eyes: 2.0, 1.2-3.3), endocrine impairment (growth hormone deficiency: 83.9, 33.0-213.6; hypothyroidism: 6.9, 4.1-11.3; need for medications to induce puberty: 90.4, 30.2-270.5), cardiopulmonary impairment (congestive heart failure: 43.0, 12.7-145.5; angina-like symptoms: 2.0, 1.3-2.9), neurosensory impairment (legal blindness: 9.8, 4.8-20.0; abnormal sensations: 1.5, 1.0-2.2), and neuromotor impairment (repeated seizures: 2.3, 1.2-4.4; motor problems: 3.7, 2.2-6.4; problems chewing or swallowing: 3.8, 1.9-7.5). CONCLUSIONS: Survivors are at risk for developing sequelae many years after their initial diagnosis and treatment. Continued medical surveillance is necessary to ensure the long-term health and well-being of RMS survivors.

Adolescent↗

Reliability, effect size, and responsiveness of health status measures in the design of randomized and cluster-randomized trials.

BACKGROUND: New health status survey instruments are often described by their psychometric (measurement) properties, such as Validity, Reliability, Effect Size, and Responsiveness. For cluster-randomized trials, another important statistic is the Intraclass Correlation (ICC) for the instrument within clusters. Studies using better instruments can be performed with smaller sample sizes, but better instruments may be more expensive in terms of dollars, opportunity cost, or poorer data quality due to the response burden of longer instruments. METHODS: We defined the psychometric statistics in terms of a mathematical model, and examined the power of a two-sample test as a function of the test-retest Reliability, Effect Size, Responsiveness, and Intraclass Correlation of the instrument. We examined the "cost-effectiveness" of using a one-item versus a five-item measure of mental health status. FINDINGS: Under the standard model for measurement error, the psychometric statistics are all functions of the same error term. They are also functions of the setting in which they were estimated. In randomized trials, power is a function of Reliability and sample size, and a less reliable instrument can achieve the desired power if N is increased. In cluster-randomized trials, adequate power may be obtained by increasing the number of clusters per treatment group (and often the number of persons per cluster), as well as by choosing a more reliable instrument. The one-item measure of mental health status may be more cost-effective than the five-item measure in some situations. CONCLUSION: If the goal is to diagnose or refer individual patients, an instrument with high Validity and Reliability is needed. In settings where the sample sizes are large or can be increased easily, any valid instrument may be cost-effective. It is likely that many published values of psychometric statistics are accurate only in settings similar to that in which they were estimated.

Cost-Benefit Analysis↗

Evaluation of matrix-assisted laser desorption/ionization-time of flight mass spectrometry proteomic profiling: identification of alpha 2-HS glycoprotein B-chain as a biomarker of diet.

Biomarkers have the potential to impact a wide range of public health concerns, including early detection of diseases, drug discovery, and improved accuracy of monitoring effects of interventions. Given new technological developments, broad-based screening approaches will likely advance biomarker discovery at an accelerated pace. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) allows for the elucidation of individual protein masses from a complex mixture with high throughput. We have developed a method for identifying serum biomarkers using MALDI-TOF and statistical analysis. However, before applying this approach to screening of complex diseases, we evaluated the approach in a controlled dietary intervention study. In this study, MALDI-TOF spectra were generated using samples from a randomized controlled trial. During separate feeding periods, 38 participants ate a basal diet devoid of fruits and vegetables and a basal diet supplemented with cruciferous (broccoli) family vegetables. Serum samples were obtained at the end of each 7-day feeding period and treated to remove large, abundant proteins. MALDI-TOF spectra were analyzed using peak picking algorithms and logistic regression models. Our bioinformatics methods identified two significant peaks at m/z values of 2740 and 1847 that could classify participants based on diet (basal vs. cruciferous) with 76% accuracy. The 2740 m/z peak was identified as the B-chain of alpha 2-HS glycoprotein, a serum protein previously found to vary with diet and be involved in insulin resistance and immune function.

Adult↗

Hepatitis B awareness, testing, and knowledge among Vietnamese American men and women.

Southeast Asians have higher rates of liver cancer than any other racial/ethnic group in the United States. Chronic carriage of hepatitis B virus (HBV) is the most common underlying cause of liver cancer in the majority of Asian populations. Our objectives were to describe Vietnamese Americans' awareness of hepatitis B, levels of HBV testing, and knowledge about hepatitis B transmission; and to compare the HBV knowledge and practices of men and women. A community-based, in-person survey of Vietnamese men and women was conducted in Seattle during 2002. Seven hundred and fifteen individuals (345 men and 370 women) completed the questionnaire. Eighty-one percent of the respondents had heard of hepatitis B (76% of men, 86% of women) and 67% reported HBV testing (66% of men, 68% of women). A majority of the participants knew that HBV can be transmitted during sexual intercourse (71% of men, 68% of women), by sharing toothbrushes (67% of men, 77% of women), and by sharing razors (59% of men, 67% of women). Less than one-half knew that hepatitis B is not spread by eating food prepared by an infected person (46% of men, 27% of women), nor by coughing (39% of men, 25% of women). One-third of our respondents did not recall being tested for HBV. Important knowledge deficits about routes of hepatitis B transmission were identified. Continued efforts should be made to develop and implement hepatitis B educational campaigns for Vietnamese immigrant communities. These efforts might be tailored to male and female audiences.

Adult↗

Cancer preventive screening: a cross-border comparison of United States and Canadian Chinese women.

OBJECTIVE: To compare screening mammography and Pap testing among Chinese women in Seattle, Washington to Vancouver, and British Columbia. METHODS: Using community-based sampling methods, trilingual female interviewers surveyed Chinese women in Seattle and Vancouver. Multiple preventive health behaviors and health care access variables were assessed. Mammography analysis included 409 women aged 50-74 years. Pap testing analysis included 973 women aged 20-69 years. Main outcome measures were ever use and use in the last 2 years of screening mammography and Pap testing. RESULTS: Chinese women in Vancouver were younger, more educated and fluent in English. Unadjusted rates of mammography and Pap testing were similar between the two cities. Provider type was consistently associated with screening in both cities; female providers had the highest rates and Chinese male providers the lowest. Adjusted logistic regression analysis demonstrated similar mammography use in the two cities. However, for Pap testing, women in Seattle had higher odds of screening compared to Vancouver. CONCLUSION: Despite universal health care coverage and baseline characteristics typically associated with greater utilization of preventive screening services, Chinese women in Vancouver did not have higher rates of screening mammography and Pap testing compared to Chinese women in Seattle.

Age Factors↗

Effects of exercise on metabolic risk variables in overweight postmenopausal women: a randomized clinical trial.

OBJECTIVE: This study examined the effects of exercise on metabolic risk variables insulin, leptin, glucose, and triglycerides in overweight/obese postmenopausal women. RESEARCH METHODS AND PROCEDURES: Sedentary women (n = 173) who were overweight or obese (BMI > or = 25 kg/m(2) or > or =24 kg/m(2) with > or =33% body fat), 50 to 75 years of age, were randomized to 12 months of exercise (> or =45 minutes of moderate-intensity aerobic activity 5 d/wk) or to a stretching control group. Body composition (DXA) and visceral adiposity (computed tomography) were measured at baseline and 12 months. Insulin, glucose, triglycerides, and leptin were measured at baseline and 3 and 12 months. Insulin resistance was evaluated by the homeostasis model assessment formula. Differences from baseline to follow-up were calculated and compared across groups. RESULTS: Exercisers had a 4% decrease and controls had a 12% increase in insulin concentrations from baseline to 12 months (p = 0.0002). Over the same 12-month period, leptin concentrations decreased by 7% among exercisers compared with remaining constant among controls (p = 0.03). Homeostasis model assessment scores decreased by 2% among exercisers and increased 14% among controls from baseline to 12 months (p = 0.0005). The exercise effect on insulin was modified by changes in total fat mass (trend, p = 0.03), such that the exercise intervention abolished increases in insulin concentrations associated with gains in total fat mass. DISCUSSION: Regular moderate-intensity exercise can be used to improve metabolic risk variables such as insulin and leptin in overweight/obese postmenopausal women. These results are promising for health care providers providing advice to postmenopausal women for lifestyle changes to reduce risk of insulin resistance, coronary heart disease, and diabetes.

Adipose Tissue↗

Associations between reproductive and menstrual factors and postmenopausal androgen concentrations.

BACKGROUND: Reproductive and menstrual characteristics, as well as high circulating estrogen and androgen concentrations, are associated with the risk of breast and ovarian cancer in postmenopausal women. To explore possible etiological relationships between menstrual and reproductive characteristics and cancer risk, we examined associations between menstrual and reproductive factors and serum concentrations of total testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S). METHODS: This study was conducted in 167 postmenopausal women, using data from the pre-randomization visit of an exercise clinical trial. Participants were sedentary, overweight/ obese, and not on hormone therapy. RESULTS: DHEA-S concentrations were 42% higher, total testosterone concentrations were 35% lower, and free testosterone concentrations were 23% lower in women with both ovaries removed compared with those with both remaining (p = 0.01, p = 0.01, and p = 0.03, respectively). Women who had used herbal therapy in the past had, on average, 25% higher concentrations of total and free testosterone than women who had never used these herbal therapies (p = 0.03 and p = 0.004, respectively). No other significant associations were detected. CONCLUSIONS: Overall, this study does not support the hypothesis that reproductive or menstrual factors, with the exception of oophorectomy status, are associated with postmenopausal androgen concentrations.

Aged↗

Associations among circulating sex hormones, insulin-like growth factor, lipids, and mammographic density in postmenopausal women.

OBJECTIVE: Hormone therapy use has been positively associated with mammographic density in several studies. However, few studies have examined the association between endogenous hormone levels and mammographic density. Therefore, we evaluated the relationship of endogenous sex hormones, insulin-like growth factor (IGF), and lipids with mammographic density in 88 overweight, postmenopausal women not taking hormone therapy. METHODS: Percent density and dense area were evaluated as continuous measures using a computer-assisted program. We used multiple linear regression to evaluate the associations of sex hormones, IGF, and cholesterol with mammographic density, adjusting for confounders, including adiposity. We evaluated stratification by history of hormone therapy use (former versus never) and hormone therapy latency (<5 versus > or = 5 years). RESULTS: Among former hormone therapy users, mammographic density was inversely associated with circulating levels of estrone (P = 0.01), estradiol (P = 0.003), free estradiol (P = 0.004), testosterone (P = 0.04), free testosterone (P = 0.02), androstenedione (P < 0.001), dehydroepiandrosterone (P = 0.01), and the ratio of IGF-I to its binding protein (IGF-I/IGFBP-3; P = 0.04). We found similar associations when we limited the analyses to women who had used hormone therapy within the past 5 years. We also noted positive associations of mammographic density with total cholesterol (P = 0.03) and low-density lipoprotein (P = 0.03) among former hormone therapy users. No associations were noted among women who had never used hormone therapy. CONCLUSIONS: These results suggest that there is an inverse relationship between endogenous sex hormones and mammographic density in postmenopausal women among former users of hormone therapy. This is not consistent with the hormone therapy literature and should be confirmed in larger studies.

Aged↗

Increased risk of cancer among siblings of long-term childhood cancer survivors: a report from the childhood cancer survivor study.

We determined risk of cancer among first-degree relatives of 5-year survivors of childhood leukemia, lymphoma, central nervous system tumors, sarcomas, Wilms' tumor, and neuroblastoma. Subjects were 13,703 participants in the Childhood Cancer Survivor Study. Family history was collected on 56,759 first-degree relatives using a self-reported questionnaire. Incidence was compared with age- and sex-specific rates using the U.S. Surveillance, Epidemiology and End Results program. Siblings of the survivors had an increased risk of cancer [standardized incidence ratio (SIR), 1.5; 95% confidence interval (95% CI), 1.35-1.7]. Risk was elevated for siblings of probands of leukemia (SIR, 1.3; 95% CI, 1.0-1.6), Hodgkin's disease (SIR, 1.5; 95% CI, 1.2-1.9), non-Hodgkin's lymphoma (SIR, 1.8; 95% CI, 1.3-2.5), Wilms' tumor (SIR, 1.9; 95% CI, 1.2-3.2), soft tissue sarcoma (SIR, 1.5; 95% CI, 1.0-2.2), and bone tumors (SIR, 1.6; 95% CI, 1.2-2.2). Cancer risk was elevated in siblings (SIR, 2.4; 95% CI, 1.5-3.7) and offspring (SIR, 15.0; 95% CI, 5.3-42.9) of probands with second malignant neoplasms (SMN) compared with relatives of probands without SMNs. Siblings of probands with leukemia, Hodgkin's disease, neuroblastoma, and Wilms' tumor had elevated risks for the same malignancies. Parents had no increased risk (fathers' SIR, 0.7; 95% CI, 0.7-0.8; mothers' SIR, 0.9; 95% CI, 0.9-1.0). Seventy percent of siblings' cancers developed in adulthood. These findings suggest that familial cancer syndromes may be revealed as this cohort and family members age and with accrual of more offspring and subjects with SMNs.

Child↗

Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility.

BACKGROUND: Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer. METHODS: Two sequential experimental phases were conducted to establish interlaboratory calibration and standardization of the surface-enhanced laser desorption (SELDI) instrumental and assay platform output. We first established whether the output from multiple calibrated Protein Biosystem II SELDI-ionization time-of-flight mass spectrometry (TOF-MS) instruments demonstrated acceptable interlaboratory reproducibility. This was determined by measuring mass accuracy, resolution, signal-to-noise ratio, and normalized intensity of three m/z "peaks" present in a standard pooled serum sample. We next evaluated the ability of the calibrated and standardized instrumentation to accurately differentiate between selected cases of prostate cancer and control by use of an algorithm developed from data derived from a single site 2 years earlier. RESULTS: When the described standard operating procedures were established at all laboratory sites, the across-laboratory measurements revealed a CV for mass accuracy of 0.1%, signal-to-noise ratio of approximately 40%, and normalized intensity of 15-36% for the three pooled serum peaks. This was comparable to the intralaboratory measurements of the same peaks. The instrument systems were then challenged with sera from a selected group of 14 cases and 14 controls. The classification agreement between each site and the established decision algorithm were examined by use of both raw peak intensity boosting and ranked peak intensity boosting. All six sites achieved perfect blinded classification for all samples when boosted alignment of raw intensities was used. Four of six sites achieved perfect blinded classification with ranked intensities, with one site passing the criteria of 26 of 28 correct and one site failing with 19 of 28 correct. CONCLUSIONS: These results demonstrate that "between-laboratory" reproducibility of SELDI-TOF-MS serum profiling approaches that of "within-laboratory" reproducibility as determined by measuring discrete m/z peaks over time and across laboratories.

Calibration↗

Hepatitis B knowledge and testing among Vietnamese-American women.

The study objective was to examine factors associated with previous hepatitis B virus (HBV) testing among Vietnamese women. A population-based survey was conducted in Seattle. The survey was completed by 370 women (response rate: 82%). Sixty-eight percent of the respondents reported previous HBV testing. Only 44% recalled a physician recommendation for the test. The following factors were associated with previous testing in bivariate comparisons: knowing that HBV can be spread during childbirth, during sexual intercourse, and by sharing toothbrushes; doctor(s) had recommended testing; family member(s) and friend(s) had suggested testing; and family member(s) were chronically infected with HBV. In a multiple regression analysis, women who reported a previous physician recommendation had nearly a five times higher odds of testing than those who did not. Education about HBV transmission may stimulate Vietnamese women to seek testing. Intervention strategies that target social networks might be effective in increasing testing levels. Physicians should be educated about the importance of testing Asian immigrants for HBV.

Adolescent↗

Human plasma ghrelin levels increase during a one-year exercise program.

Weight loss resulting from decreased caloric intake raises levels of the orexigenic hormone, ghrelin. Because ingested nutrients suppress ghrelin, increased ghrelin levels in hypophagic weight loss may result from decreased inhibitory input by ingested food, rather than from lost weight. We assessed whether ghrelin levels increase in response to exercise-induced weight loss without decreased caloric intake. We randomized 173 sedentary, overweight, postmenopausal women to an aerobic exercise intervention or stretching control group. At baseline, 3 months, and 12 months, we measured body weight and composition, food intake, cardiopulmonary fitness (maximal oxygen consumption), leptin, insulin, and ghrelin. Complete data were available for 168 women (97%) at 12 months. Exercisers lost 1.4 +/- 0.4 kg (P < 0.05 compared with baseline; P = 0.01 compared with stretchers) and manifested a significant, progressive increase in ghrelin levels, whereas neither measure changed among stretchers. Ghrelin increased 18% in exercisers who lost more than 3 kg (P < 0.001). There was no change in caloric intake in either group and no effect on ghrelin of exercise per se independent of its impact on body weight. In summary, ghrelin levels increase with weight loss achieved without reduced food intake, consistent with a role for ghrelin in the adaptive response constraining weight loss and, thus, in long-term body weight regulation.

Body Mass Index↗

Methylenetetrahydrofolate reductase genotype affects risk of relapse after hematopoietic cell transplantation for chronic myelogenous leukemia.

PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) directs intracellular folate toward homocysteine metabolism and away from nucleotide synthesis. Two common MTHFR polymorphisms, C677T and A1298C, are associated with reduced enzyme activity. We evaluated the association of these polymorphisms with risk of relapse and bcr-abl mRNA transcript detection among 336 Caucasian patients who underwent allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia. EXPERIMENTAL DESIGN: Data on the transplant course and folate-related exposures were abstracted from medical records. MTHFR C677T and A1298C genotypes were determined using polymerase chain reaction/restriction fragment length polymorphism and TaqMan assays. Qualitative bcr-abl mRNA testing was conducted using a two-step reverse transcription-polymerase chain reaction assay. Cox regression analysis was used to assess the association between MTHFR genotypes and time to relapse and bcr-abl mRNA detection. RESULTS: A statistically significant decreased risk of relapse was observed in patients with the variant A1298C genotype [1298AC, hazard ratio (HR)=0.48 and 95% confidence interval (CI)=0.26-0.88; 1298CC, HR=0.28 and 95% CI=0.09-0.84; P-trend <0.01). For the joint C677T/A1298C genotype, variant genotypes were associated with a decreased risk of relapse when compared with the wild-type 677CC/1298AA genotype. This risk was lowest for the 677CC/1298CC genotype (HR, 0.23; 95% CI, 0.08-0.72). MTHFR genotypes were not associated with bcr-abl transcript detection. CONCLUSIONS: These findings suggest that individuals with the 677CC/1298AA genotype are at higher risk of relapse after hematopoietic cell transplantation and that the balance of intracellular folate metabolites available for nucleotide synthesis (regulated by the relative activity of the MTHFR enzyme) may affect the progression from bcr-abl positivity to clinical relapse.

Adolescent↗

Breast cancer after childhood cancer: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Survivors of childhood cancer are at risk for secondary breast cancer. Other than previous chest radiation therapy, risk factors for secondary breast cancer have not been established. OBJECTIVE: To identify risk factors for breast cancer among female survivors of childhood cancer. DESIGN: Retrospective cohort study. SETTING: The Childhood Cancer Survivor Study (CCSS), a multicenter study of persons who survived more than 5 years after childhood cancer diagnosed from 1970 to 1986. PARTICIPANTS: Among 6068 women in the CCSS, 95 women had 111 confirmed cases of breast cancer. MEASUREMENTS: Standardized incidence ratios for breast cancer were calculated by using age-specific incidence rates in the general population. Breast cancer incidence was evaluated with respect to primary cancer diagnosis and therapy, age at and time since primary diagnosis, menstrual and reproductive history, and family history of cancer. RESULTS: Breast cancer risk was increased in survivors who were treated with chest radiation therapy (standardized incidence ratio, 24.7 [95% CI, 19.3 to 31.0]) and survivors of bone and soft-tissue sarcoma who were not treated with chest radiation therapy (standardized incidence ratios, 6.7 and 7.6, respectively). Family history of breast cancer (relative rate, 2.7 [CI, 1.3 to 5.0]) and history of thyroid disease (relative rate, 1.7 [CI, 1.1 to 2.6]) were independently associated with increased risk, and exposure to pelvic radiation was protective (relative rate, 0.6 [CI, 0.4 to 0.9]). Age at primary cancer diagnosis and menstrual and reproductive histories did not statistically significantly modify risk. LIMITATIONS: This cohort has not yet attained an age at which breast cancer risk is greatest. CONCLUSION: Survivors of childhood sarcomas and those who received chest radiation therapy are at risk for secondary breast cancer. When assessing a survivor's risk, clinicians should consider primary diagnosis, previous radiation therapy, family cancer history, and history of thyroid disease.

Adult↗