Interest and informational preferences regarding genomic testing for modest increases in colorectal cancer risk.

BACKGROUND/AIMS: This study explored the interest in genomic testing for modest changes in colorectal cancer risk and preferences for receiving genomic risk communications among individuals with intermediate disease risk due to a family history of colorectal cancer. METHODS: Surveys were conducted on 272 men and women at intermediate risk for colorectal cancer enrolled in a randomized trial comparing a remote personalized risk communication intervention (TeleCARE) aimed at promoting colonoscopy to a generic print control condition. Guided by Leventhal's Common Sense Model of Self-Regulation, we examined demographic and psychosocial factors possibly associated with interest in SNP testing. Descriptive statistics and logistic regression models were used to identify factors associated with interest in SNP testing and preferences for receiving genomic risk communications. RESULTS: Three-fourths of participants expressed interest in SNP testing for colorectal cancer risk. Testing interest did not markedly change across behavior modifier scenarios. Participants preferred to receive genomic risk communications from a variety of sources: printed materials (69.5%), oncologists (54.8%), primary-care physicians (58.4%), and the web (58.1%). Overall, persons who were unmarried (p = 0.029), younger (p = 0.003) and with greater cancer-related fear (p = 0.019) were more likely to express interest in predictive genomic testing for colorectal cancer risk. In a stratified analysis, cancer-related fear was associated with the interest in predictive genomic testing in the intervention group (p = 0.017), but not the control group. CONCLUSIONS: Individuals with intermediate familial risk for colorectal cancer are highly interested in genomic testing for modest increases in disease risk, specifically unmarried persons, younger age groups and those with greater cancer fear.

Trisomic pregnancy and intermediate CGG repeat length at the FMR1 locus.

BACKGROUND: We hypothesized that trisomy arises as a function of the size of the oocyte pool, with risk increased among women with diminished pools. Diminished pools may cause primary ovarian failure, which has been associated with premutation and intermediate CGG repeat length at the Fragile X mental retardation (FMR1) locus. Thus, we hypothesized that the risk of trisomic pregnancy is increased among women with intermediate CGG repeat length on the FMR1 gene. METHODS: The analysis drew on data from two hospital-based case-control studies. We compared 207 women with trisomic spontaneous abortions (SAs) to three comparison groups: 82 women with other chromosomally abnormal SAs, 99 women with chromosomally normal SAs and 537 women with live births (LBs), age matched to women with SAs. We defined the length of the CGG repeat in four ways: the biallelic mean, the genotypic mean, the length on allele 2 and the length on allele 1. We analyzed CGG repeat length as a categorical variable. All analyses were adjusted for site, age and ethnicity. RESULTS: CGG repeat length did not differ significantly between women with trisomic SAs and any of the three comparison groups. For the biallelic mean, the adjusted odds ratio relating trisomy (versus LB controls) to the highest category (35.5-59.5 repeats) versus the modal category (26.5-30.0 repeats) was 1.5 (95% confidence interval (CI): 0.7, 3.1). Comparisons with the two SA control groups also showed increased odds of more repeats among trisomy cases. Results were similar when repeat length was defined by the genotypic mean or by the repeat length on allele 2. For allele 1, the odds of short (9-19) repeat length were lower, but not significantly so, for trisomy cases compared with LB controls. Excluding women with premutations (n= 2) from the analysis yielded an adjusted odds ratio of 1.4 (95% CI: 0.7, 2.9) for the biallelic mean. CONCLUSIONS: Our data are equivocal. The direction of associations is consistent with the hypothesis that repeat length in the intermediate range is associated with trisomy. However, differences between the trisomy cases and the comparison groups are neither large nor statistically significant. Our data rule out odds ratios larger than about 3.

Copy number changes on the X chromosome in women with and without highly skewed X-chromosome inactivation.

AIM: To test the hypothesis that microdeletions or microduplications below the resolution of a standard karyotype may be a significant cause of highly skewed X-inactivation (HSXI) in women without a cytogenetically detected X-chromosome anomaly. METHODS: Cases were women with HSXI, defined as ≥85% of cells in a blood sample with the same active allele at the HUMARA locus. The skewing in controls ranged from 50 to <75%. We performed an SNP microarray analysis using the Affymetrix 6.0 platform for 45 cases and 45 controls. RESULTS: Cases and controls did not differ in the frequency of X-chromosome copy number changes ≥100 kb or in the frequency of copy number changes that contained genes. However, one woman with HSXI >90% in blood and left and right buccal smears had a 5.5-Mb deletion in Xp22.2p22.1. This deletion could affect the viability of male conceptions and may have led to the dysmorphology found in female carriers. CONCLUSION: HSXI in a blood sample is rarely due to X-chromosome copy number changes detectable by microarray.

Trisomic pregnancy and elevated FSH: implications for the oocyte pool hypothesis.

BACKGROUND: Some studies, but not all, support the hypothesis that trisomy frequency is related to the size of the oocyte pool, with the risk increased for women with fewer oocytes (older ovarian age). We tested this hypothesis by comparing hormonal indicators of ovarian age among women who had trisomic pregnancy losses with indicators among women with non-trisomic losses or chromosomally normal births. The three primary indicators of advanced ovarian age were low level of anti-Müllerian hormone (AMH), high level of follicle-stimulating hormone (FSH) and low level of inhibin B. METHODS: The analysis drew on data from two hospital-based case-control studies. Data were analyzed separately and the evidence from the two sites was combined. We compared 159 women with trisomic pregnancy losses to three comparison groups: 60 women with other chromosomally abnormal losses, 79 women with chromosomally normal losses and 344 women with live births (LBs) age-matched to women with losses. We analyzed the hormone measures as continuous and as categorical variables. All analyses adjust for age in single years, day of blood draw, interval in storage and site. RESULTS: AMH and inhibin B did not differ between women with trisomic losses and any of the three comparison groups. Mean ln(FSH) was 0.137 units (95% confidence interval (CI): 0.055, 0.219) higher for trisomy cases compared with LB controls; it was also higher, though not significantly so, for trisomy cases compared with women with other chromosomally abnormal losses or chromosomally normal losses. The adjusted odds ratio in relation to high FSH (≥ 10 mIU/ml) was significantly increased for trisomy cases versus LB controls (adjusted odds ratio (OR): 3.8, 95% CI: 1.6, 8.9). CONCLUSIONS: The association of trisomy with elevated FSH is compatible with the oocyte pool hypothesis, whereas the absence of an association with AMH is not. Alternative interpretations are considered, including the possibility that elevated FSH may disrupt meiotic processes or allow recruitment of abnormal follicles.

National scientific facilities and their science impact on nonbiomedical research.

The "h index" proposed by Hirsch [Hirsch JE (2005) Proc Natl Acad Sci USA 102:16569-16573] is a good indicator of the impact of a scientist's research and has the advantage of being objective. When evaluating departments, institutions, or laboratories, the importance of the h index can be further enhanced when it is properly calibrated for the size of the group. Particularly acute is the issue of federally funded facilities whose number of actively publishing scientists frequently dwarfs that of academic departments. Recently, Molinari and Molinari [Molinari JF, Molinari A (2008) Scientometrics, in press] developed a methodology that shows that the h index has a universal growth rate for large numbers of papers, allowing for meaningful comparisons between institutions. An additional challenge when comparing large institutions is that fields have distinct internal cultures, with different typical rates of publication and citation; biology is more highly cited than physics, for example. For this reason, the present study has focused on the physical sciences, engineering, and technology and has excluded biomedical research. Comparisons between individual disciplines are reported here to provide a framework. Generally, it was found that the universal growth rate of Molinari and Molinari holds well across the categories considered, testifying to the robustness of both their growth law and our results. The goal here is to set the highest standard of comparison for federal investment in science. Comparisons are made of the nation's preeminent private and public institutions. We find that many among the national science facilities compare favorably in research impact with the nation's leading universities.

Smoking, alcohol and caffeine in relation to ovarian age during the reproductive years.

BACKGROUND: We sought to determine whether smoking, alcohol and caffeine are related to four indicators of ovarian age: antral follicle count (AFC), follicle stimulating hormone (FSH), inhibin B and estradiol. METHODS: Analyses drew on ultrasound scans and sera from 188 women, aged 22-49. We used least squares regression to estimate differences in AFC and hormone levels for women who smoke cigarettes or who drink alcohol or caffeine. RESULTS: Current smoking is related to elevated FSH (beta for ln(FSH) = 0.21, 95% CI 0.04, 0.39), but not to AFC, inhibin B or estradiol. Neither alcohol nor caffeine is related to any ovarian age indicator. Exploratory analyses suggest that the association of current smoking with FSH varies with age: comparing current with never smokers, at ages 30, 35, 40 and 45, estimated differences in mean FSH are 0.3, 1.3, 3.2 and 6.9 mIU/ml. CONCLUSIONS: The association of current smoking with FSH may reflect accelerated oocyte atresia, impaired follicle quality or dysregulation of the hypothalamic-pituitary-ovarian axis. Identification of the causal mechanism has implications for prevention or treatment of conception delay, infertility and morbidity associated with early menopause.

Predictors of antral follicle count during the reproductive years.

BACKGROUND: We sought to identify indicators of antral follicle count which would be serviceable to clinicians seeking to estimate the number of ovarian follicles without relying on sonographic counts. METHODS: We examined the relations of chronological age and four potential indicators of ovarian age-ovarian volume, FSH, dimeric inhibin B and estradiol-to antral follicle count in 176 recently pregnant women. We identified the regression models which best predict low antral follicle count (< or =10 follicles). RESULTS: Chronological age, ovarian volume, FSH and inhibin B were each significantly associated with antral follicle count. Fifty-three (30.1%) women had < or =10 antral follicles. In the total sample, at the cutpoint corresponding to 80% sensitivity, the positive predictive value for a regression model with all four variables was 60%. All regression models performed less well in women <35 years (13.9% with low count) than in women > or =35 years (52.0% with low count). In older women, the positive predictive value for the model with all four variables was 79%, compared with 60% for a model with chronological age alone. CONCLUSIONS: Our models provide a basis for advising women aged > or =35 years who are either trying to conceive or wish to learn whether they may postpone childbearing.

Trisomic pregnancy and the oocyte pool.

BACKGROUND: We tested the hypothesis that trisomy risk is increased for women with fewer oocytes (older ovarian age) than other women of the same chronological age. METHODS: Our study compared three indicators of ovarian age-number of antral follicles, level of dimeric inhibin B, level of FSH-among women who had trisomic pregnancy losses (n = 54) with those among women who had other losses (24 with other chromosomally abnormal loses, 21 with chromosomally normal losses) or who had chromosomally normal births (n = 65). RESULTS: Ovarian age indicators did not differ between women with trisomic spontaneous abortions and the three comparison groups. Compared with live birth controls, adjusting for chronological age, we estimate that, on average, among trisomy cases the geometric means of 1 + follicle count, inhibin B and FSH are about 7.5% higher, 16.6% higher and 5.5% lower, respectively, with all 95% confidence intervals including zero. The sample size was sufficient to detect moderate differences (0.52 standard errors of regression) between trisomy cases and live birth controls. CONCLUSIONS: Although our data do not support our hypothesis, they leave open the possibility that changes in follicular development unrelated to the size of the oocyte pool influence abnormal chromosome segregation.

Factors associated with colorectal cancer screening in a population-based study: the impact of gender, health care source, and time.

INTRODUCTION: The effectiveness of colorectal cancer screening in reducing incident colorectal cancer and the risk of death has been shown. Despite campaigns to promote the benefits of and use of colorectal cancer screening, most people are not participating in screening. In this paper, we examine factors associated with screening behavior over time, by health care provider, and by gender and report associations between screening and development of colorectal cancer after adjusting for diet and lifestyle factors. METHODS: Data from two population-based case-control studies of colorectal cancer were used to examine risk associations with nonparticipation in colorectal cancer screening. Study participants were identified for the first study between 1991 and 1994 (N = 1,346 cases and 1,544 controls) and for the second between 1997 and 2001 (N = 952 cases and 1,205 controls) and were asked to complete a detailed in-person interviewer-administered diet and lifestyle questionnaire. The control population is used to examine changes in screening behavior and associations with screening over time. RESULTS: Significantly, fewer people reported fecal occult blood test (FOBT) in 1997-2001 than in 1991-1994 (62.5% in 1991-1994 vs. 47.2% in 1997-2001); a slight nonsignificant increase in sigmoidoscopy screening was reported for these periods among controls (33.9% vs. 36.6%). In the control population, during these periods, there was a statistically significant increase in the number of people who reported having had a sigmoidoscopy for screening rather than for problems (72.6% in 1997-2001 vs. 63.8% in 1991-1994). There were differences in factors associated with screening behavior by time, by sex, and by health care provider, although having a family history of colorectal cancer, having more education, and being male was associated with more screening in all settings. After adjusting for diet and lifestyle factors, we observed that non-sigmoidoscopy screening significantly influenced risk of incident cancer (rectal OR: 2.9; 95% CI, 2.3-3.7; distal tumor OR: 1.8; 95% CI, 1.4-2.3); proximal tumor: 1.4; 95% CI, 1.1-1.8). Nonuse of FOBT also was associated significantly with tumors in the rectal (OR: 1.6; 95% CI, 1.3-1.9) and distal (OR: 1.4; 95% CI, 1.1-1.8) sites. SUMMARY: These data reinforce the importance of screening to reduce risk of colorectal cancer development. However, flexible sigmoidoscopy screening is increasing only modestly over time, and primarily in settings where a significant investment in screening has been made. FOBT screening, which is effective for rectal cancer prevention, is actually decreasing.

Manipulating desaturase activities in transgenic crop plants.

The properties of edible vegetable oils are determined to a large extent by the relative content of the triacylglycerol fatty acids. The degree of saturation of these fatty acids can determine the functional, sensory and nutritional value of the oil. One method of altering the unsaturated fatty acid content of oilseeds is by manipulating the expression of desaturase genes of these plants. Manipulating the expression of desaturase genes in transgenic crops such as soybean, maize and canola (oilseed rape) has led to oils with improved functionality and nutrition. We have also been successful in manipulating the fatty acid content of domesticated oilseed plants by expressing heterologous desaturase and desaturase-related genes from exotic plants that produce unusual fatty acids. We have discovered that metabolic regulation, the number of genetic alleles that encode fatty acid biosynthetic enzymes, and the movement of fatty acids between complex lipids in the cell, all have a role in determining the effect of a transgene on the phenotype of the crop plant and the fatty acid composition of its seed oil.

Knowledge, attitudes, and interest in breast-ovarian cancer gene testing: a survey of a large African-American kindred with a BRCA1 mutation.

BACKGROUND: This study assessed counseling and testing needs from the perspective of adult members of a large African-American kindred with a BRCA1 mutation. METHODS: Interviews were conducted with 95 male and female kindred members to elicit information on sociodemographics, attitudes toward health care providers, breast cancer screening behaviors, and religious/spiritual beliefs, as well as to evaluate psychological distress, beliefs, knowledge, and attitudes related to genetic testing. RESULTS: Knowledge about breast and ovarian cancer genetics was limited. Adherence to screening recommendations was low among females with no personal breast or ovarian cancer history. The majority (67%) wished to discuss risk factors with a health care provider. Most participants (82%) indicated that they would have a genetic test if it were available. Significant predictors of intent to undergo testing were having at least one first-degree relative with breast and/or ovarian cancer (OR = 5.1; 95% CI = 1.2-20.9) and perceived risk of being a gene carrier > or =50% (OR = 64.3; 95% CI = 5.1-803.9) or reporting that they did not know their risk of being a gene carrier (OR = 10.9; 95% CI = 2.1-57.7). Cited barriers to testing included cost and availability. CONCLUSION: There is a high interest level in genetic testing despite limited knowledge about cancer genetics among these high-risk African Americans. Our study provides information for designing a genetic education and counseling intervention for this and similar families.

Cosuppression of the alpha subunits of beta-conglycinin in transgenic soybean seeds induces the formation of endoplasmic reticulum-derived protein bodies.

The expression of the alpha and alpha' subunits of beta-conglycinin was suppressed by sequence-mediated gene silencing in transgenic soybean seed. The resulting seeds had similar total oil and protein content and ratio compared with the parent line. The decrease in beta-conglycinin protein was apparently compensated by an increased accumulation of glycinin. In addition, proglycinin, the precursor of glycinin, was detected as a prominent polypeptide band in the protein profile of the transgenic seed extract. Electron microscopic analysis and immunocytochemistry of maturing transgenic soybean seeds indicated that the process of storage protein accumulation was altered in the transgenic line. In normal soybeans, the storage proteins are deposited in pre-existing vacuoles by Golgi-derived vesicles. In contrast, in transgenic seed with reduced beta-conglycinin levels, endoplasmic reticulum (ER)-derived vesicles were observed that resembled precursor accumulating-vesicles of pumpkin seeds and the protein bodies accumulated by cereal seeds. Their ER-derived membrane of the novel vesicles did not contain the protein storage vacuole tonoplast-specific protein alpha-TIP, and the sequestered polypeptides did not contain complex glycans, indicating a preGolgi and nonvacuolar nature. Glycinin was identified as a major component of these novel protein bodies and its diversion from normal storage protein trafficking appears to be related to the proglycinin buildup in the transgenic seed. The stable accumulation of proteins in a protein body compartment instead of vacuolar accumulation of proteins may provide an alternative intracellular site to sequester proteins when soybeans are used as protein factories.

Genetic testing for colorectal carcinoma susceptibility: focus group responses of individuals with colorectal carcinoma and first-degree relatives.

BACKGROUND: Colorectal carcinoma (CRC) may be the most frequent form of hereditary cancer. Genetic counseling and testing for heritable CRC is a promising approach for reducing the high incidence and mortality rates associated with the disease. Patients with CRC or those with at least one family member with the disease are the most likely persons to request or be offered genetic testing in the clinical or research setting. Currently, however, little is known about the behavioral, psychosocial, ethical, legal, and economic outcomes of CRC genetic counseling and testing. METHODS: Eight focus group interviews, four for CRC patients (n = 28) and four for first-degree relatives (n = 33), were conducted to obtain insights into attitudes, beliefs, and informational needs about genetic testing for hereditary CRC. RESULTS: Focus group interviews revealed a general lack of knowledge about cancer genetics and genetic testing; worry about confidentiality issues; strong concern for family members, particularly children; and a need for primary care providers to be informed about these issues. Major perceived advantages of genetic testing included improving health-related decisions, guiding physicians in making recommendations for surveillance, and informing relatives about risk potential. Disadvantages included potential discrimination, adverse psychologic effects, and financial costs associated with testing. CONCLUSIONS: As knowledge and media coverage of genetics continue to expand, it becomes increasingly important to continue efforts on behalf of, and in partnership with, those individuals most affected by genetic testing for hereditary cancer syndromes. These findings provide data needed to develop and implement informational, educational, counseling, and research-oriented programs that are sensitive to individuals' concerns and preferences.

Formation of conjugated delta8,delta10-double bonds by delta12-oleic-acid desaturase-related enzymes: biosynthetic origin of calendic acid.

Divergent forms of the plant Delta(12)-oleic-acid desaturase (FAD2) have previously been shown to catalyze the formation of acetylenic bonds, epoxy groups, and conjugated Delta(11),Delta(13)-double bonds by modification of an existing Delta(12)-double bond in C(18) fatty acids. Here, we report a class of FAD2-related enzymes that modifies a Delta(9)-double bond to produce the conjugated trans-Delta(8),trans-Delta(10)-double bonds found in calendic acid (18:3Delta(8trans,10trans,12cis)), the major component of the seed oil of Calendula officinalis. Using an expressed sequence tag approach, cDNAs for two closely related FAD2-like enzymes, designated CoFADX-1 and CoFADX-2, were identified from a C. officinalis developing seed cDNA library. The deduced amino acid sequences of these polypeptides share 40-50% identity with those of other FAD2 and FAD2-related enzymes. Expression of either CoFADX-1 or CoFADX-2 in somatic soybean embryos resulted in the production of calendic acid. In embryos expressing CoFADX-2, calendic acid accumulated to as high as 22% (w/w) of the total fatty acids. In addition, expression of CoFADX-1 and CoFADX-2 in Saccharomyces cerevisiae was accompanied by calendic acid accumulation when induced cells were supplied exogenous linoleic acid (18:2Delta(9cis,12cis)). These results are thus consistent with a route of calendic acid synthesis involving modification of the Delta(9)-double bond of linoleic acid. Regiospecificity for Delta(9)-double bonds is unprecedented among FAD2-related enzymes and further expands the functional diversity found in this family of enzymes.

Cocaine- and alcohol-mediated expression of inducible transcription factors is blocked by pentobarbital anesthesia.

Identifying the neurocircuitry involved in behavioral responses to drugs of abuse is an important step towards understanding the mechanisms of drug addiction. The present study sought to distinguish brain regions involved in pharmacological effects of cocaine and ethanol from secondary effects by administering these drugs in the presence or absence of pentobarbital anesthesia. Changes in neuronal activity were assessed by immunohistochemical analysis of expression of an inducible transcription factor (ITF), c-Fos, in the brain of rats habituated to repeated pentobarbital anesthesia or saline administration. Cocaine administration (15 mg/kg, i.v.) in non-anesthetized animals produced a strong induction of c-Fos in the striatum and large number of other brain areas. Ethanol administration (2 g/kg, i.p.) induced c-Fos in a smaller number of characteristic brain areas, including the central nucleus of amygdala and paraventricular nucleus of hypothalamus. However, neither of these drugs was able to induce c-Fos in pentobarbital-anesthetized rats (50 mg/kg, i.v.). The suppressive effects of pentobarbital were not specific to c-Fos, such that pentobarbital also suppressed expression of ITFs FosB and Egr1 in the striatum of cocaine-treated rats. On the other hand, pentobarbital by itself strongly induced c-Fos expression in the lateral habenula of saline-, cocaine-, and ethanol-injected rats. It is not clear whether the suppressive effects of anesthesia on ITF expression in other areas are mediated by activation of lateral habenula, or are independent of this event. Our data suggest that in the absence of conscious awareness of drug-associated cues, cocaine and alcohol activate only a fraction of the neural elements engaged in the unanesthetized state.

Production of fatty acid components of meadowfoam oil in somatic soybean embryos.

The seed oil of meadowfoam (Limnanthes alba) and other Limnanthes spp. is enriched in the unusual fatty acid Delta(5)-eicosenoic acid (20:1Delta(5)). This fatty acid has physical and chemical properties that make the seed oil of these plants useful for a number of industrial applications. An expressed sequence tag approach was used to identify cDNAs for enzymes involved in the biosynthesis of 20:1Delta(5)). By random sequencing of a library prepared from developing Limnanthes douglasii seeds, a class of cDNAs was identified that encode a homolog of acyl-coenzyme A (CoA) desaturases found in animals, fungi, and cyanobacteria. Expression of a cDNA for the L. douglasii acyl-CoA desaturase homolog in somatic soybean (Glycine max) embryos behind a strong seed-specific promoter resulted in the accumulation of Delta(5)-hexadecenoic acid to amounts of 2% to 3% (w/w) of the total fatty acids of single embryos. Delta(5)-Octadecenoic acid and 20:1Delta(5) also composed <1% (w/w) each of the total fatty acids of these embryos. In addition, cDNAs were identified from the L. douglasii expressed sequence tags that encode a homolog of fatty acid elongase 1 (FAE1), a beta-ketoacyl-CoA synthase that catalyzes the initial step of very long-chain fatty acid synthesis. Expression of the L. douglassi FAE1 homolog in somatic soybean embryos was accompanied by the accumulation of C(20) and C(22) fatty acids, principally as eicosanoic acid, to amounts of 18% (w/w) of the total fatty acids of single embryos. To partially reconstruct the biosynthetic pathway of 20:1Delta(5) in transgenic plant tissues, cDNAs for the L. douglasii acyl-CoA desaturase and FAE1 were co-expressed in somatic soybean embryos. In the resulting transgenic embryos, 20:1Delta(5) and Delta(5)-docosenoic acid composed up to 12% of the total fatty acids.

The motor core of speech: a comparison of serial organization patterns in infants and languages.

Comparison of serial organization of infant babbling and early speech with that of 10 languages reveals four movement-related design features reflecting a deep evolutionary heritage: (1) the cyclical consonant-vowel alternation underlying the syllable, a "Frame" for speech consisting of mandibular oscillation, possibly evolving from ingestive cyclicities (e.g., chewing) via visuofacial communicative cyclicities (e.g., lipsmacks); (2) three intracyclical consonant-vowel co-occurrence preferences reflecting basic biomechanical constraints-coronal consonants-front vowels, dorsal consonants-back vowels, and labial consonants-central vowels; (3) a developmental progression from above-chance to below-chance levels of intercyclical consonant repetition; (4) an ease-related labial consonant-vowel-coronal consonant sequence preference for word initiation. These design features presumably result from self-organizational responses to selection pressures, primarily determined by motor factors. No explanation for these design features is available from Universal Grammar, and, except for feature 3, perceptual-motor learning seems to have only a limited causal role in acquisition of any design feature.

Alcohol consumption and breast cancer among black and white women in North Carolina (United States).

OBJECTIVE: The purpose of this study was to investigate the effects of alcohol consumption on breast cancer risk in black and white women. METHODS: We used data from the Carolina Breast Cancer Study, a population-based, case-control study of black and white women in North Carolina. Interviews were conducted with 890 cases and 841 controls frequency-matched on age and race. RESULTS: Overall, the prevalence of moderate to high levels of alcohol consumption was low. Compared with abstainers, the multivariate odds ratio for recent intake of one or two drinks per day was 1.4 (95% CI = 0.9-2.1) and two or more drinks a day was 1.0 (95% CI = 0.6-1.6); increasing consumption was not associated with risk (p for trend = 0.6). The associations were similar, but somewhat weaker, for average lifetime consumption. Among women who consumed 91 g/week or more of alcohol, a nonsignificant increased risk of breast cancer was observed for women reporting binge drinking (OR = 1.5; 95% CI = 0.9-2.3), but not for those who consumed less than 91 g/week reporting binge drinking (OR = 1.0; 95% CI = 0.6-1.5). Odds ratios did not differ meaningfully by race, age, menopausal status, exogenous hormone use, or body mass index. CONCLUSIONS: These data provide little evidence for an association between alcohol consumption and risk of breast cancer among either black or white women.

Trisomic pregnancy and earlier age at menopause.

We tested the hypothesis that the connection between advanced maternal age and autosomal trisomy reflects the diminution of the oocyte pool with age. Because menopause occurs when the number of oocytes falls below some threshold, our hypothesis is that menopause occurs at an earlier age among women with trisomic pregnancies than it does among women with chromosomally normal pregnancies. To determine their menstrual status, we interviewed women from our previous study of karyotyped spontaneous abortions who, in 1993, were age >/=44 years. Premenopausal women completed interviews every 4-5 mo, until menopause or until the study ended in 1997. The primary analyses compare 111 women whose index pregnancy was a trisomic spontaneous abortion with two groups: women whose index pregnancy was a chromosomally normal loss (n=157) and women whose index pregnancy was a chromosomally normal birth (n=226). We used a parametric logistic survival analysis to compare median ages at menopause. The estimated median age at menopause was 0.96 years earlier (95% confidence interval -0.18 to 2.10) among women with trisomic losses than it was among women with chromosomally normal losses and chromosomally normal births combined. Results were unaltered by adjustment for education, ethnicity, and cigarette smoking. Our results support the hypothesis that trisomy risk is increased with decreased numbers of oocytes. Decreased numbers may indicate accelerated oocyte atresia or fewer oocytes formed during fetal development.