Influence of a 12-month supervised, intensive resistance, aerobic and impact exercise intervention on muscle strength in prostate cancer patients undergoing anti-hormone therapy: Study protocol for the randomized, controlled Burgdorf study.

INTRODUCTION: Reduced testosterone levels due to androgen deprivation therapy (ADT) in prostate cancer patients cause common side effects, such as reduced muscle strength and bone density, increased fat mass, sexual dysfunction and fatigue. Short-term exercise during ADT has proven to be safe and effective in exhibiting a positive impact on body composition, sexual dysfunction and fatigue. However, there are only three randomized controlled trials that investigate one-year supervised impact exercise interventions, none of which examined follow-up effects after the intervention. Therefore, this study will conduct a one-year impact exercise intervention and assess follow-up effects up to one year later. MATERIAL AND METHODS: The aim of the randomized, controlled Burgdorf study is to assess the effects of a supervised 12-month intensive multimodal exercise intervention in comparison to a moderate aerobic exercise intervention, on muscle strength in prostate cancer patients receiving ADT. Additionally, quality of life, fatigue, body composition, erectile dysfunction, bone pain, physical activity level, endurance capacity, body-mass-index, waist and hip circumference and prostate-specific antigen- and testosterone levels will be assessed up to one year later. DISCUSSION: The Burgdorf study is the first study to conduct two different one-year supervised exercise interventions, and follow-up with patients for up to one year after the intervention. Results could provide important insights into the long-term effects of interventions on those parameters negatively affected by ADT, which could specify or newly establish care structures. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00009975. Registered 2016-02-09, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009975.

Self-reported functional outcome after surgical intervention in patients with idiopathic normal pressure hydrocephalus.

The goal of this study was to characterize long-term social and functional outcomes in adults treated for idiopathic normal pressure hydrocephalus (NPH). Data for 252 patients treated medically or surgically for idiopathic NPH were obtained through the Hydrocephalus Association Database Project. Data on post-surgical outcomes including improvement in symptoms, the need for in-home care, ability to drive, and employment status were analyzed. Most patients (73.7%) surveyed were treated with a shunt, an endoscopic third ventriculostomy (ETV), or both. More patients who underwent surgery reported driving and being employed compared to those who did not have surgery. Most shunt patients had improvements in gait (81.1%), urinary incontinence (55.9%), and dementia (64.4%). Overall, shunt patients reported more dramatic improvements in quality of life as compared to ETV patients (72.2% versus 55.6%). Treating idiopathic NPH with cerebrospinal fluid diversion facilitates a return to independence through improved functional and social outcomes.

Molecular typing of human leukocyte antigen and related polymorphisms following whole genome amplification.

Reliable, high-resolution genotyping of human leukocyte antigen (HLA) polymorphisms is often compromised by DNA samples of suboptimal quality or limited quantity. We tested the feasibility of molecular typing for variants at HLA and neighboring loci using whole genome amplification (WGA) strategy facilitated by the Phi29 DNA polymerase. With little (5-100 ng) starting genomic DNA of varying quality and source materials, WGA was deemed successful in 167 of 169 DNA from 47 cell lines, 100 European Americans, and 22 native Africans. The Phi29-processed DNA provided adequate templates for polymerase chain reaction (PCR)-based analyses of several HLA (A, B, C, DRB1, and DQB1) and related loci (HFE, MICA, and 10 microsatellites) in the 6p24.3-6p21.3 region, with PCR amplicons ranging from 92 to 2200 bp. Five different genotyping techniques resolved and confirmed 364 genotypes when both original and Phi29-processed DNA worked in PCRs. General population genetic analyses provided additional evidence that WGA may represent a reliable and simple approach to securing ample genomic DNA for typing HLA, MICA, and related variants.

Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid.

BACKGROUND: We previously showed that women with abnormal cytology in breast fluid obtained by nipple aspiration had an increased relative risk (RR) of breast cancer compared with women from whom fluid was not obtained and with women whose fluid had normal cytology. This study extends the follow-up in the original study group (n = 4046) and presents the first follow-up for a second group of women (n = 3627). METHODS: We collected nipple aspirate fluid from women in the San Francisco Bay Area during the period from 1972 through 1991, classified the women according to the most severe epithelial cytology observed in fluid specimens, and determined breast cancer incidence through March 1999. We estimated RRs for breast cancer using Cox regressions, adjusting for age and year of study entry. All statistical tests were two-sided. RESULTS: For women in the first and second study groups, the median years of follow-up were 21 years and 9 years, respectively, and breast cancer incidences were 7.8% (285 cases in the 3633 women for whom breast cancer status could be determined) and 3.5% (115 of 3271), respectively. Compared with women from whom no fluid was obtained, whose incidences of breast cancer were 4.7% (39 of 825) and 3.3% (65 of 1950) for those in group 1 and group 2, respectively, incidences and adjusted RRs were 8.1% (34 of 422), with RR = 1.4 (95% confidence interval [CI] = 0.9 to 2.3), and 0% (0 of 31), respectively, for those with unsatisfactory aspirate specimens and 8.2% (148 of 1816), with RR = 1.6 (95% CI = 1.1 to 2.3), and 3.1% (25 of 811), with RR = 1.2 (95% CI = 0.8 to 2.0), respectively, for those with normal cytology in aspirates. Compared with women from whom no fluid was obtained, incidences and adjusted RRs for women in group 1 with epithelial hyperplasia and atypical hyperplasia in aspirates were 10.8% (52 of 483), with RR = 2.4 (95% CI = 1.6 to 3.7), and 13.8% (12 of 87), with RR = 2.8 (95% CI = 1.5 to 5.5), respectively, while those for women in group 2 were 5.5% (25 of 457) and 0% (0 of 22), respectively, with a combined RR = 2.0 (95% CI = 1.3 to 3.3). CONCLUSION: The results obtained with the newly followed women independently confirmed previous findings that women with abnormal cytology in nipple aspirates of breast fluid have an increased risk of breast cancer.

Prevalence of antibodies to four herpesviruses among adults with glioma and controls.

The authors previously reported statistically significant inverse associations between adult onset glioma and histories of chickenpox and shingles among 462 cases and 443 controls in the San Francisco Bay Area Adult Glioma Study (1991--1995) and a suggestive but nonsignificant inverse association with immunoglobulin G antibodies to varicella-zoster virus in a small subset of these cases. This report considers antibodies to four common herpesviruses (varicella zoster, herpes simplex, cytomegalovirus, and Epstein Barr) among 134 cases and 165 controls that represent all subjects for whom usable blood specimens were available. The prevalences of immunoglobulin G antibodies to varicella-zoster virus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were 90%, 71%, 57%, and 90%, respectively. After adjustment for age, White versus non-White ethnicity, and gender, glioblastoma cases were less likely than controls to have immunoglobulin G antibodies to varicella-zoster virus (odds ratio = 0.4; 95% confidence interval: 0.1, 0.9). They were also somewhat less likely to have antibodies to Epstein-Barr virus but somewhat more likely to have antibodies to herpes simplex virus and cytomegalovirus. Antibody prevalences to all four herpesviruses were similar between cases with other glioma histologies and controls. These results corroborate our previously suggestive findings of an inverse association of varicella-zoster virus antibodies with adult onset glioma.

Ethnicity delineates different genetic pathways in malignant glioma.

In the United States and the San Francisco Bay Area, whites are nearly twice as likely as non-whites to develop brain cancer. To test whether prevalence and types of alterations in the p53 pathway in brain tumor development may explain some of this difference in risk, we have analyzed the p53 status of astrocytic gliomas from a population-based sample of cases within our San Francisco Bay Area Adult Glioma Study. We identified mutations in exons 5-8 of p53 using DNA extracted from formalin-fixed paraffin-embedded tissue blocks from 146 whites and 26 non-whites with astrocytic glioma by PCR-single-strand conformation polymorphism and direct sequencing. Tumor P53 protein (TP53) immunohistochemistry (IHC) available for 164 of these cases showed that tumors from 50% (13 of 26) of non-whites and 32% (44 of 138) of whites contained intense IHC staining for TP53, indicating persistence of TP53 protein. Irrespective of IHC status, tumors from 42% (11 of 26) of non-whites versus 13% (19 of 146) of whites contained p53 mutations (age/gender-adjusted odds ratio, 5.7; 95% confidence interval, 2.2-15.1; P = 0.0004). Patients with p53 mutation-positive tumors were also significantly younger than patients with mutation-negative tumors and somewhat more likely to be female. A higher proportion of tumors from non-whites than from whites had transition mutations, but there were similar proportions of transversion mutations in tumors from whites and non-whites. Whites and non-whites also had similar proportions of tumors with p53 mutations that stained intensely for TP53 (78 and 82%, respectively). Because whites have higher risk for glioma than non-whites in this population, that the gliomas from whites were less likely than those from non-whites to have p53 mutation suggests that whites may be more likely than non-whites to be at risk for the more common type of astrocytic gliomas, which do not contain p53 mutations.

Associations between ERCC2 polymorphisms and gliomas.

Xeroderma pigmentosum complementation group D/excision repair cross-complementing in rodents 2 (ERCC2) encodes a protein that is part of the nucleotide excision repair pathway and the transcription factor IIH transcription complex. Mutations in this gene have been shown to cause three distinct clinical diseases including xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Several ERCC2 polymorphisms, the effects of which on gene function are not known, have been described. To investigate whether constitutive sequence variations might be associated with adult onset gliomas, blood specimens from a case-control study (187 cases and 169 controls) were genotyped for seven previously described polymorphisms (R156R, I199M, H201Y, D312N, A575A, D711D, and K751Q). A novel R616C polymorphism was also identified. Cases were significantly more likely than controls to be homozygous for the silent AA variant at codon 156 (odds ratio, 2.3; 95% confidence interval, 1.3-4.2). Although this was observed for patients in each of three histological subgroups of cases, (glioblastoma multiforme, astrocytoma, and oligoastrocytoma) compared with controls, the association was strongest for patients with oligoastrocytoma (odds ratio, 3.2; 95% confidence interval, 1.1-9.5). In contrast, cases were somewhat less likely than controls to carry variants at D312N, D711D, and K751Q, but not significantly so overall or for any subgroup after adjustment for age and gender. Individuals with variant nucleotides at D312N, D711D, and K751Q were significantly more likely to carry a variant at another of those three codons and less likely to carry a variant nucleotide at R156R, regardless of case or control status. Although the pattern of association observed here is consistent with a role of ERCC2 variants in the prevention or causation of glioma, these results are also consistent with the possibility that another gene linked to ERCC2 may be involved. This seems especially so because the strongest association was observed with a silent nucleotide variation.

Genetic resistance factor for HIV-1 and immune response to varicella zoster virus.

A 32 bp deletion in the chemokine receptor CCR5 gene modulates HIV-1 infection. However, whether this CCR5 gene variation modifies immunity to common herpesvirus infections is unknown. We investigated whole blood IgG concentrations of 157 normal adult blood donors. Also we assessed whether the 32 bp deletion of CCR5 (delta32CCR5) was associated with circulating IgG to four herpesviruses: varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus type 1 and type 2. Individuals who carried delta32CCR5 were 9.2 times more likely to be seronegative for varicella zoster virus than non-carriers (95% CI 2.9-29.1), but no differences were seen for the other herpesviruses studied. Variation in CCR5 may modulate humoral immunity to varicella zoster virus.

Dietary calcium consumption and astrocytic glioma: the San Francisco Bay Area Adult Glioma Study, 1991-1995.

Previous studies suggest an association between calcium consumption and glioma risk. In the present study, we compare consumption of calcium and other dairy components and foods (cholesterol, fat, protein, calories, milk, and cheese) of 337 astrocytic glioma case patients with 450 controls from the San Francisco Bay Area Adult Glioma Study, 1991-1995. We use unconditional logistic regression models to estimate odds ratios (ORs) by gender controlling for age, education, and income. A statistically significant inverse association [p (trend) = 0.05] was observed for dietary calcium intake for women only [OR = 0.49, 95% confidence interval (CI) = 0.24-1.03 for highest vs. lowest quartile of consumption]. In addition, we observed elevated ORs for highest vs. lowest quartiles of cholesterol intake among women and men (OR = 2.07, 95% CI = 1.00-4.28 and OR = 1.75, 95% CI = 0.92-3.31, respectively). Calcium may exert a protective effect through its known roles in apoptosis, DNA repair, and inhibition of parathyroid hormone production. Recent evidence suggests that parathyroid hormone may influence growth and dedifferentiation of astrocytoma cells. Finally, circulating estradiol might directly stimulate intestinal absorption of calcium and may therefore explain why the inverse association of calcium intake and glioma is confined to women.

Occupation and adult gliomas.

Lifetime job histories from a population-based, case-control study of gliomas diagnosed among adults in the San Francisco Bay area between August 1991 and April 1994 were evaluated to assess occupational risk factors. Occupational data for 476 cases and 462 controls were analyzed, with adjustment for age, gender, education, and race. Imprecise increased risks were observed for physicians and surgeons (odds ratio (OR) = 3.5, 95% confidence interval (CI): 0.7, 17.6), artists (OR = 1.9, 95% CI: 0.5, 6.5), foundry and smelter workers (OR = 2.6, 95% CI: 0.5, 13.1), petroleum and gas workers (OR = 4.9, 95% CI: 0.6, 42.2), and painters (OR = 1.6, 95% CI: 0.5, 4.9). Legal and social service workers, shippers, janitors, motor vehicle operators, and aircraft operators had increased odds ratios only with longer duration of employment. Physicians and surgeons, foundry and smelter workers, petroleum and gas workers, and painters showed increased risk for both astrocytic and nonastrocytic tumors. Artists and firemen had increased risk for astrocytic tumors only, while messengers, textile workers, aircraft operators, and vehicle manufacturing workers showed increased risk only for nonastrocytic tumors. Despite study limitations, including small numbers for many of the occupational groups, a high percentage of proxy respondents among cases, and lack of specific exposure information, associations were observed for several occupations previously reported to be at higher risk for brain tumors generally and gliomas specifically.

Are prior head injuries or diagnostic X-rays associated with glioma in adults? The effects of control selection bias.

The causes of glioma, the most common type of primary malignant brain tumors, are poorly understood. This study compares personal histories of head injury and diagnostic radiation procedures of the head and neck among 476 adults newly diagnosed with glioma in the San Francisco Bay Area between August of 1991 and April of 1994 (82% of all those diagnosed during that time period) with 462 age-, gender-, and ethnicity-frequency-matched controls (63% of those eligible from random digit dialing). In addition, limited information was obtained from 101 controls during a brief telephone interview conducted with controls who declined participation in the lengthy in-person interview. Controls who participated in the full interview were much more likely than controls who only completed the telephone interview to report head injury [odds ratios (OR) and 95% confidence intervals (CI) were 2.3 (1.0-4.9) and 3.0 (1.6-5.8) for women and men, respectively]. The OR for any head injury in cases versus controls who completed the full interview was 0.9. However, OR for any head injury in cases versus both control groups was 1.3, 95% CI (1.0-1.7), and the OR for head injury for which the subject sought medical attention was 1.1, 95% CI (0.8-1.4). Among subjects completing the full interview, cases who responded by self-report were less likely than controls to report prior non-dental head and neck X-rays (OR = 0.7; 95% CI: 0.5-1.0). However, stratification by respondents' history of head injury indicated no difference in history of head and neck X-ray among those without prior head injury; OR 0.9; 95% CI (0.6-1.2). Cases and controls shared a very similar history of dental procedures and frequency of dental visits. These results suggest that head injury requiring medical attention, dental visits, or non-dental diagnostic X-rays to the head and neck are not important contributors to the risk of adult glioma and reveal some of the methodological obstacles encountered in forming convincing conclusions about these risk factors for brain tumors.

Association of an ERCC1 polymorphism with adult-onset glioma.

Gliomas include several histologically distinct types of tumors whose molecular profiles suggest different etiologies. Because the ERCC1 protein is essential for nucleotide excision repair and influences genomic instability, polymorphisms in ERCC1 may play a role in human tumors. We determined the presence of the A versus C polymorphism at nucleotide 8092 of ERCC1 using a single-strand conformational polymorphism assay and DNA sequencing in adults with glioma and controls from a population-based study. Among 318 alleles from 159 controls, 27% (86) were A and 73% were C. Prevalences of the CC genotype were 51% (81 of 159), 48% (30 of 62), 63% (20 of 32), and 82% (23 of 28) for controls and subjects with glioblastoma multiforme, astrocytoma, and oligoastrocytoma, respectively (Fisher's exact P = 0.009). The age-adjusted odds ratio for genotype CC in all cases versus controls was 1.4 (95% confidence interval, 0.9-2.3), whereas that for subjects with oligoastrocytoma versus controls was 4.6 (95% confidence interval, 1.6-13.2). The median age at diagnosis was 46 years for glioma patients with the CC genotype compared with 54 years for patients with the AA or AC genotype (P = 0.04). This is the first study to report a significant association of a polymorphism in ERCC1 with the risk of brain tumors. This A/C polymorphism, which may affect mRNA stability for ERCC1, also results in an amino acid substitution of lysine to glutamine in a recently described nucleolar protein (ASE-1) and T-cell receptor complex subunit CD3epsilon-associated signal transducer (CAST). This finding, if confirmed in other series, may provide a foundation on which to study novel mechanisms of carcinogenesis in subsets of glioma.

Discrepancies in diagnoses of neuroepithelial neoplasms: the San Francisco Bay Area Adult Glioma Study.

BACKGROUND: Valid and reliable diagnoses of disease are key both to meaningful epidemiologic and clinical investigations and to decision-making about appropriate treatment. One previous study highlighted the lack of precision in diagnosing primary brain tumors in a neuropathology referral practice. The current study explores diagnostic discrepancies in a population-based adult glioma series by hospital of origin, specialty training of the original diagnosing pathologist, and clinical significance. METHODS: To confirm patients' eligibility for the San Francisco Adult Glioma Study, the authors obtained participants' pathology specimens and conducted a uniform secondary neuropathology review. Eligible patients were all adults age 20 years or older newly diagnosed with glioma between August 1, 1991, and March 31, 1994, who resided in 1 of 6 San Francisco Bay Area counties. RESULTS: Overall, the original and secondary diagnoses were the same (concordant) for 352 (77%) of the 457 cases available for study. Twenty-six percent of the cases from community hospitals were discordant, compared with 12% of the cases from academic hospitals P= 0.004. Of the 105 discordant diagnoses, 17 (16%) were determined to be clinically significant, defined as a difference that could significantly alter patient management and/or prognosis. Sixteen of these 17 cases originated at community hospitals, and only 1 originated at a hospital with a neuropathologist. Based on the distribution of review diagnoses, subjects presenting at nonacademic hospitals were more likely than those presenting at academic hospitals to have glioblastoma (61% vs. 52%; P = 0.07). CONCLUSIONS: The percentage of cases with discrepant original and review diagnoses was higher among those originally diagnosed at community hospitals without a neuropathologist than among those originally diagnosed at an academic hospital with a neuropathologist. Clinically significant discrepancies were much more likely to have originated at a community hospital without a neuropathologist. These data highlight the importance of review of brain tumors by a neuropathologist prior to decision-making regarding treatment. A separate implication of this study is that glioma cases selected exclusively from academic or nonacademic institutions in a particular geographic area are unlikely to be representative of all cases occurring in that area.

Alternative therapies used by women with breast cancer in four ethnic populations.

BACKGROUND: Interest in alternative therapies is growing rapidly in the United States. We studied the types and prevalence of conventional and alternative therapies used by women in four ethnic groups (Latino, white, black, and Chinese) diagnosed with breast cancer from 1990 through 1992 in San Francisco, CA, and explored factors influencing the choices of their therapies. METHODS: Subjects (n = 379) completed a 30-minute telephone interview in their preferred language. Logistic regression models assessed factors associated with the use of alternative therapies after a diagnosis of breast cancer. RESULTS: About one half of the women used at least one type of alternative therapy, and about one third used two types; most therapies were used for a duration of less than 6 months. Both the alternative therapies used and factors influencing the choice of therapy varied by ethnicity. Blacks most often used spiritual healing (36%), Chinese most often used herbal remedies (22%), and Latino women most often used dietary therapies (30%) and spiritual healing (26%). Among whites, 35% used dietary methods and 21% used physical methods, such as massage and acupuncture. In general, women who had a higher educational level or income, were of younger age, had private insurance, and exercised or attended support groups were more likely to use alternative therapies. About half of the women using alternative therapies reported discussing this use with their physicians. More than 90% of the subjects found the therapies helpful and would recommend them to their friends. CONCLUSIONS: Given the high prevalence of alternative therapies used in San Francisco by the four ethnic groups and the relatively poor communication between patients and doctors, physicians who treat patients with breast cancer should initiate dialogues on this topic to better understand patients' choices with regard to treatment options.

Lack of association of rare alleles in the HRAS variable number of tandem repeats (VNTR) region with adult glioma.

HRAS rare alleles have been associated with the increased susceptibility to a variety of cancers. In the present study we examined the hypothesis that HRAS rare alleles are a risk factor for adult glioma in a population-based case-control study of adult glioma in six San Francisco Bay Area counties. We compared the prevalence of rare alleles in the variable number of tandem repeats region of HRAS in the germline DNA from 73 white adults who had gliomas with that of 65 controls. Overall, the prevalence of rare alleles in cases was not different from the prevalence of those in controls according to two definitions of rare alleles. We found that 25 of 73 (34%) of cases versus 25 of 65 (38%) of controls had at least one allele that was not 30, 46, 69, or 87 repeats; 4 of 73 (5%) of cases versus 6 of 65 (9%) of controls carried one or more alleles with 33, 39, 42, 53, 59, 63, 68, 105, or 114 repeats. The proportion of rare alleles was somewhat higher among subjects with anaplastic astrocytoma. Among women, cases were less likely than controls to have HRAS rare alleles, whereas among men, cases were slightly more likely to have HRAS rare alleles, but none of these results approach statistical significance. Our data do not suggest an excess of HRAS rare alleles among adult glioma cases.

Adult glioma in relation to residential power frequency electromagnetic field exposures in the San Francisco Bay area.

In a population-based study, we examined residential power frequency electromagnetic field exposures for 492 adults newly diagnosed with histologically confirmed glioma between August 1, 1991 and April 30, 1994, in the San Francisco Bay area and 462 controls, obtained through random-digit dialing frequency, matched to cases for age, gender, and race. Residential exposure assessment consisted of spot measures with EMDEX (Enertech Consultants, Campbell, CA) meters and wire codes based on characterization and location of nearby power lines. We considered the index residence at the time of the case's diagnosis or the control's interview and all other California residences of each subject for 7 years before study entry. We obtained wire codes for eligible residences of 76% and for index residences of 99% of subjects. Using the Kaune-Savitz wire code classification, the relative risk for longest held residences coded as "high" compared with "low" was 0.9 [95% confidence interval (CI) = 0.7-1.3], while relative risk and 95% CIs for front door spot measures of 1.01-2 milligauss, 2.01-3 milligauss, and higher than 3 milligauss compared with < or =1 milligauss were 1.0 (0.7-1.4), 0.6 (0.3-1.1), and 1.7 (0.8-3.6). Adjustment for age, gender, race, and whether the subject owned the residence did not meaningfully alter these findings, nor did comparisons using index or highest coded residence. Because of potential exposure misclassification and the unknown pertinent exposure period, these data cannot provide strong support against, but clearly do not support an association between, adult glioma and residential power frequency electromagnetic field exposures.

Aberrant methylation of p16INK4a in anatomic and gender-specific subtypes of sporadic colorectal cancer.

Colorectal cancer (CRC) occurring in the proximal colon and among women may represent a distinct subtype of the disease. In the present study of 120 sporadic CRCs, we used methylation-specific PCR to test whether methylation of the CpG island in the 5' region of the p16INK4a tumor suppressor gene was associated with anatomical location, gender, or other clinicopathological characteristics. Overall, 18.3% of the tumors had detectable p16INK4a methylation. A marked preponderance of methylated tumors occurred within the proximal colon; cancers occurring proximal to the sigmoid colon were 13.1 times more likely to contain methylated p16INK4a compared with distal tumors. In addition, female patients were 8.8 times more likely than males to have methylation-positive cancers, and p16INK4a methylation was also associated with poorly differentiated tumors. The localization of tumors with p16INK4a methylation within the proximal colon and among female patients specifically adds to a growing database of molecular alterations that define important subtypes of sporadic CRC. The potentially reversible nature of CpG methylation may provide novel therapeutic opportunities for this increasing subtype of the disease, which, due to anatomical location, presents a great challenge for early detection.

Birthplace and yield of nipple aspirate fluid in Chinese women.

The different rates of breast cancer found between Chinese women in Asia compared with Chinese-born women in the United States suggest that dietary and environmental factors may be of etiological significance. We evaluated the proportion of 480 premenopausal Chinese women who yielded nipple aspirate fluid (NAF) by birthplace in Asia versus the United States and by reproductive and other risk factors. Birthplace was used as a surrogate for presumed differences in exposures during gestation, childhood, and adolescence that might influence yield of NAF in premenopausal women. In United States-born Chinese women compared with Asia-born Chinese women, the proportion yielding NAF was 44 of 95 (46.3%) versus 120 of 385 (31.2%), respectively. The relative risk of yield of NAF in United States-born women compared with Asia-born women was odds ratio = 2.37 (95% confidence interval, 1.26-4.47). Independent positive associations of NAF yield were also found with history of parity and breast feeding, cerumen phenotype, and a negative association with ever use of oral contraceptives. These findings support the hypothesis that early environmental exposures may have long-lasting physiological effects discernible in the breast glands of adult women.

p53 mutations in malignant gliomas.

A population-based series of incident cases of malignant glioma were analyzed for mutations in the tumor suppressor gene p53. Exons 4-8 were screened using PCR-single-strand conformation analysis and confirmed through direct sequencing. Of 62 tumors analyzed, 12 (19%) contained mutations in p53: one 18-bp duplication in exon 5, five point mutations in exon 4, three point mutations in exon 7, two point mutations in exon 8, and a splice-site mutation at the exon 6/intron 7 boundary. In contrast to previous studies of malignant glioma, the prevalence of transversion mutations (56%) was higher than transition mutations (33%). A large proportion of transversion mutations occurred in exon 4, a region that is not routinely screened in gliomas. We present here an improved method for screening exon 4 (and other GC-rich regions) of p53 using PCR-single-strand conformation analysis. The high frequency of transversion mutations suggests a role for exogenous carcinogens in the etiology of malignant glioma.