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Isabel dos Santos Silva

Publications and source records attributed to Isabel dos Santos Silva.

18 recordsLinked to original sources
PubMed2006

Lack of evidence on diets for obesity for children: a systematic review.

BACKGROUND: The prevalence of obesity has increased rapidly in most developed countries in the last decades, and this rise is now spreading to developing countries. Childhood obesity is also increasing. The UK government has set a target to halt the rise in childhood obesity by 2010. Dietary recommendations are a central component of any comprehensive weight-loss programme. A low-fat energy-restricted diet is the conventional therapy for obesity, but alternative dietary interventions have been proposed in recent years. METHODS: We conducted a systematic review to assess dietary intervention studies designed to reduce weight in childhood and adolescence. The studies included overweight or obese children or adolescents in which there was a comparison group and change in body weight or BMI was reported. RESULTS: We identified only nine such studies, seven of which were randomized. Six were conducted in the USA, two in Cuba, and one in France. Low-carbohydrate and low-glycaemic-index diets appeared to be at least as effective as energy-restricted low-fat diets for short-term weight loss, but most studies were too small to be informative, and none provided evidence on long-term weight control. CONCLUSIONS: There is a marked mismatch between the public health importance of childhood obesity and the number and quality of the studies conducted so far to assess dietary interventions for weight reduction in childhood and adolescence, and little evidence to support the current recommendation of a low-fat energy-restricted diet. There is an urgent need for well-designed intervention studies of the long-term effectiveness of alternative diets to provide a basis for evidence-based recommendations.

Adolescent↗
PubMed2006

Inconsistent association between the STK15 F31I genetic polymorphism and breast cancer risk.

STK15 may be a low-penetrance breast cancer susceptibility gene, and several reports suggest that women who are homozygous for the polymorphic variant F31I have an increased risk of breast cancer. To evaluate this potential breast cancer allele, we genotyped 507 patients with two primary breast cancers and 875 population-based control subjects for the STK15 F31I polymorphism. All statistical tests were two-sided. The Ile/Ile homozygous genotype was not associated with an increased risk in white women of British descent. The odds ratio for developing two primary breast cancers) in Ile/Ile homozygotes was 0.63 (95% confidence interval [CI] = 0.34 to 1.13), which corresponds to an odds ratio of 0.79 (95% CI = 0.58 to 1.06) for a first primary breast cancer. A meta-analysis of this study and other published studies showed statistically significant heterogeneity in the odds ratio estimates (P<.001). This heterogeneity could reflect either population-specific linkage disequilibrium with a functional variant or artifacts such as population stratification or publication bias.

Asian People↗
PubMed2006

Phyto-oestrogen intake and plasma concentrations in South Asian and native British women resident in England.

Phyto-oestrogens, naturally occurring hormone-like chemicals in plant food, may play a protective role against hormone-related chronic diseases. South Asian migrants in the UK have a lower incidence of hormone-related cancer than their hosts but the extent to which this difference may be due to phytoestrogen intake is not known. The aim was to compare habitual phytoestrogen intake in first-generation South Asian migrant women and native British women. South Asian (n 221) and native British women (n 50) were recruited from general practitioner lists and were asked to provide monthly 24 h recalls for a period of 1 year. An enhanced phytoestrogen database was compiled using data from a literature search and unpublished data. A sub-sample of South Asian women (n 100) and the native British women (n 40) also provided blood samples every 3 months during the 1-year period. The median daily intakes (microg/d) of isoflavones (184.2 v. 333.9) and lignans (110.8 v. 148.8) were significantly lower in South Asians than in the native British (P<0.001, P=0.04 respectively). There were no significant differences in mean plasma isoflavone levels (nmol/l) but plasma enterolactone was significantly lower in the South Asians (13.9 (SD 17.5) v. 28.5 (SD 23.3), P<0.001). The main sources of phytoestrogens were bread and vegetables in both ethnic groups. Habitual phytoestrogen intake in South Asian and native British women was below 1 mg/d and was higher in the native British diet. The present study does not support the hypothesis that differences in phytoestrogen intake, or in circulating levels, could explain differences in hormone-related cancer risks between these two populations.

Adult↗
PubMed2006

The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women.

High levels of circulating insulin-like growth factor-I (IGF-I) and its major binding protein (IGFBP-3) at premenopausal ages have been associated with an increased breast cancer risk. We conducted a cross-sectional study (215 premenopausal women and 241 after natural menopause) nested within the Guernsey prospective studies to examine the relationship between the IGF system and mammographic features of the breast. The mammographically dense area in the breast increased with increasing serum levels of IGF-I (P for linear trend, P(t) = 0.05), IGF-II (P(t) = 0.08), and IGFBP-3 (P(t) = 0.01) only in premenopausal women. IGF-II and IGFBP-3 serum levels were associated with increases in the mammographically lucent area in both premenopausal (P(t) = 0.01 and 0.04, respectively) and postmenopausal women (P(t) < 0.001 for both), but these associations were no longer statistically significant after adjustment for body mass index and waist circumference. Neither the IGF-I/IGFBP-3 nor the IGF-II/IGFBP-3 molar ratio was associated with any of these mammographic features. The number of A alleles at a polymorphic locus in the promoter region of the IGFBP-3 gene was associated with increasing mean IGFBP-3 levels in both premenopausal (P(t) = 0.01) and postmenopausal (P(t) <0.001) women but not with mammographically dense area. These results support the hypothesis that the IGF system may affect the amount of mammographically dense tissue in premenopausal women, possibly by promoting cell proliferation and inhibiting apoptosis in the fibroglandular tissue. The findings also show strong relations between IGF-II and IGFBP-3 levels and the amount of mammographically lucent tissue, reflecting the associations between body adiposity and amount of fat tissue in the breast and between body adiposity and circulating levels of these growth factors.

Adult↗
PubMed2006

Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis.

Mammographic features are associated with breast cancer risk, but estimates of the strength of the association vary markedly between studies, and it is uncertain whether the association is modified by other risk factors. We conducted a systematic review and meta-analysis of publications on mammographic patterns in relation to breast cancer risk. Random effects models were used to combine study-specific relative risks. Aggregate data for > 14,000 cases and 226,000 noncases from 42 studies were included. Associations were consistent in studies conducted in the general population but were highly heterogeneous in symptomatic populations. They were much stronger for percentage density than for Wolfe grade or Breast Imaging Reporting and Data System classification and were 20% to 30% stronger in studies of incident than of prevalent cancer. No differences were observed by age/menopausal status at mammography or by ethnicity. For percentage density measured using prediagnostic mammograms, combined relative risks of incident breast cancer in the general population were 1.79 (95% confidence interval, 1.48-2.16), 2.11 (1.70-2.63), 2.92 (2.49-3.42), and 4.64 (3.64-5.91) for categories 5% to 24%, 25% to 49%, 50% to 74%, and > or = 75% relative to < 5%. This association remained strong after excluding cancers diagnosed in the first-year postmammography. This review explains some of the heterogeneity in associations of breast density with breast cancer risk and shows that, in well-conducted studies, this is one of the strongest risk factors for breast cancer. It also refutes the suggestion that the association is an artifact of masking bias or that it is only present in a restricted age range.

Breast Neoplasms↗
PubMed2005

Statistical issues in life course epidemiology.

There is growing recognition that the risk of many diseases in later life, such as type 2 diabetes or breast cancer, is affected by adult as well as early-life variables, including those operating prior to conception and during the prenatal period. Most of these risk factors are correlated because of common biologic and/or social pathways, while some are intrinsically ordered over time. The study of how they jointly influence later ("distal") disease outcomes is referred to as life course epidemiology. This area of research raises several issues relevant to the current debate on causal inference in epidemiology. The authors give a brief overview of the main analytical and practical problems and consider a range of modeling approaches, their differences determined by the degree with which associations present (or presumed) among the correlated explanatory variables are explicitly acknowledged. Standard multiple regression (i.e., conditional) models are compared with joint models where more than one outcome is specified. Issues arising from measurement error and missing data are addressed. Examples from two cohorts in the United Kingdom are used to illustrate alternative modeling strategies. The authors conclude that more than one analytical approach should be adopted to gain more insight into the underlying mechanisms.

Causality↗
PubMed2005

Birth characteristics and adult cancer incidence: Swedish cohort of over 11,000 men and women.

Associations between larger size at birth and increased rates of adult cancer have been proposed but few empirical studies have examined this hypothesis. We investigated overall and site-specific cancer incidence in relation to birth characteristics in a Swedish population-based cohort of 11,166 singletons born in 1915-1929 for whom we have detailed obstetric data and who were alive in 1960. A total of 2,685 first primary cancers were registered during follow-up from 1960 to 2001. A standard deviation (SD) increase in birth weight for gestational age (GA) was associated with (sex-adjusted) increases of 13% (95% CI = 0.03-0.23) in the rates of digestive cancers and of 17% (95% CI = 0.01-0.35) in the rates of lymphatic cancers. Women who had higher birth weights also had increased rates of breast cancer under age 50 years (by 39% per SD increase; 95% CI = 0.09-0.79), but reduced rates (by 24%; 95% CI = 0.07-0.38) of endometrial (corpus uteri) cancer at all ages. There was no evidence of associations with other cancer sites. For overall cancer incidence, men had an 8% increased risk at all ages per SD increase in birth weight for GA while women only had an increased risk under age 50 years (mainly driven by the association with breast cancer). These findings provide evidence of a modest association of birth size and adult cancer risk, resulting from positive associations with a few cancer sites and a possible inverse association with endometrial cancer.

Adult↗
PubMed2005

Correlates of high-density mammographic parenchymal patterns by menopausal status in a rural population in Northern Greece.

Reproductive factors affect breast cancer risk, but less is known of their associations with mammographic density and whether these differ by menopausal status. We report on a cross-sectional study of 1946 pre- and 3047 post-menopausal women who joined a breast screening programme in Northern Greece during 1993-1997. The odds of having a high-density Wolfe pattern (P2/DY) was inversely associated with age (P for linear trend <0.001) in both pre- and post-menopausal women and, for post-menopausal women, with years since menopause (P < 0.001). The odds of a P2/DY pattern declined with higher parity (P < 0.001) and younger age at first pregnancy (P = 0.05) in both pre- and post-menopausal women. They also decreased with the duration of breast-feeding in pre-menopausal women (P = 0.03 in pre- and P = 0.69 in post-menopausal women; test for interaction with menopausal status: P = 0.07). Age at menarche, age at menopause and the number of miscarriages/abortions were not associated with mammographic density. Age at first pregnancy and parity were strong correlates of mammographic density in pre- and post-menopausal women while duration of breast-feeding appeared to be particularly important in pre-menopausal women.

Aged↗
PubMed2005

A semiquantitative food frequency questionnaire is a valid indicator of the usual intake of phytoestrogens by south Asian women in the UK relative to multiple 24-h dietary recalls and multiple plasma samples.

We investigated the relative validity of an interview-administered FFQ to estimate phytoestrogen intake among South Asian women in the UK. A population-based sample of 108 healthy South Asian women completed random repeated monthly 24-h recalls [with a subsample (n = 58) also providing multiple plasma samples] over a period of 1 y followed by administration of the FFQ. The FFQ produced slightly higher estimates of phytoestrogen intake than the 24-h recalls, but the percentage of women classified into the same +/- 1 quartile by the 2 methods was high for all phytoestrogens (from 81 to 94%) with only a small percentage (<5%) being misclassified into extreme opposite quartiles. Energy-adjusted Spearman correlations coefficients between the estimates obtained by the FFQ and the 24-h recalls were 0.55 for genistein, 0.60 for daidzein, 0.70 for secoisolariciresinol, and 0.63 for matairesinol (all P < 0.001). Spearman correlation coefficients between the FFQ estimates and plasma levels were 0.21 (P = 0.12) for genistein, 0.32 (P = 0.02) for daidzein and 0.10 (P = 0.43) for enterolactone; the corresponding values for the 24-h recalls compared with plasma levels were 0.43 (P < 0.001), 0.40 (P = 0.002), and 0.08 (P = 0.50), respectively. The method of triads was used to estimate the validity coefficients (VCs) between the estimates provided by each assessment method and "true intake." The FFQ had the highest VC for lignans (0.91 vs. 0.73 for 24-h recalls and 0.11 for plasma samples) and satisfactory VCs for both genistein (0.46 vs. 0.95 and 0.45, respectively) and daidzein (0.67 vs. 0.83 and 0.45, respectively). This FFQ is thus a relatively valid tool with which to estimate phytoestrogen intake among South Asian women in the UK.

Asia, Southeastern↗
PubMed2005

No Evidence for BRAF as a melanoma/nevus susceptibility gene.

Somatic mutations of BRAF have been identified in both melanoma tumors and benign nevi. Germ line mutations in BRAF have not been identified as causal in families predisposed to melanoma. However, a recent study suggested that a BRAF haplotype was associated with risk of sporadic melanoma in men. Polymorphisms or other variants in the BRAF gene may therefore act as candidate low-penetrance genes for nevus/melanoma susceptibility. We hypothesized that promoter variants would be the most likely candidates for determinants of risk. Using denaturing high-pressure liquid chromatography and sequencing, we screened peripheral blood DNA from 184 familial melanoma cases for BRAF promoter variants. We identified a promoter insertion/deletion in linkage disequilibrium with the previously described BRAF polymorphism in intron 11 (rs1639679) reported to be associated with melanoma susceptibility in males. We therefore investigated the contribution of this BRAF polymorphism to melanoma susceptibility in 581 consecutively recruited incident cases, 258 incident cases in a study of late relapse, 673 female general practitioner controls, and the 184 familial cases. We found no statistically significant difference in either genotype or allele frequencies between cases and controls overall or between male and female cases for the BRAF polymorphism in the two incident case series. Our results therefore suggest that the BRAF polymorphism is not significantly associated with melanoma and the promoter insertion/deletion linked with the polymorphism is not a causal variant. In addition, we found that there was no association between the BRAF genotype and mean total number of banal or atypical nevi in either the cases or controls.

Alleles↗
PubMed2004

Validation of a food frequency questionnaire to assess macro- and micro-nutrient intake among South Asians in the United Kingdom.

BACKGROUND: The South Asian population is one of the largest minority ethnic groups in the United Kingdom (UK), forming 2.7% of the UK population. Risk of diseases such as CHD, NIDDM is high in South Asians and risk of cancer low in this population compared both to the native UK population and other migrant groups. It is useful to investigate the experience of disease and dietary exposures for aetiological clues in South Asians. The FFQ was designed for a population-based case-control study of diet and breast cancer. AIMS: To validate a food frequency questionnaire (FFQ) to assess macro- and micronutrient intake among South Asians in the United Kingdom (UK). METHODS: A one-year long study of current diet was conducted using monthly telephone 24-hour recalls followed by administration of an interviewer-administered FFQ to ascertain usual diet during this period. General practices in the Thames and West Midlands regions, England were used to sequentially recruit 100 women from a larger random sample of South Asian migrants from general practitioners' patient lists participating as controls in a case-control study of diet and breast cancer. RESULTS: A total of 133 women were invited to achieve the final sample of 100 (76% response rate). The proportion of individuals classified by the two dietary assessment methods into the same or adjacent quartiles was high ranging from 65% (vitamin A) to 96% (protein). Misclassification into opposite quartiles was very low (0 % to 5 %), except for vitamin A (10 %). Energy-adjusted Spearman correlation coefficients were reasonable for almost all nutrients being highest for protein (0.76), NSP (0.71), folate (0.70) and cholesterol (0.69). Correction for within-person variation in monthly 24-hour recalls had little effect on the magnitude of the nutrient correlations between the FFQ and the 24-hour recalls. Calibration coefficients to correct relative risks for nutrient-disease associations were above 0.50 for most nutrients indicating that the degree of attenuation introduced by the FFQ would be acceptable. CONCLUSIONS: This FFQ was specifically designed for South Asian women in the UK. Despite the diversity of diets, the FFQ had reasonable validity. The role of diet in breast cancer disease aetiology in this population is being assessed with this instrument.

Adult↗
PubMed2004

Phyto-oestrogen intake and breast cancer risk in South Asian women in England: findings from a population-based case-control study.

OBJECTIVE: This study investigates whether intake of phyto-oestrogens is associated with breast cancer risk in South Asian women from the Indian subcontinent, whose diet is rich in pulses and vegetables but poor in soyfoods. METHODS: A total of 240 South Asian breast cancer cases living in England and 477 age-matched population-based controls were recruited into the study. Dietary intake was measured using a validated food frequency questionnaire. Conditional logistic regression models were used to estimate the effect of phyto-oestrogen intake on breast cancer risk. RESULTS: After adjustment for known breast cancer risk factors and total energy intake, there was moderate evidence of a dose-effect response in the odds of breast cancer with isoflavone intake (p-value for trend 0.08), with women in the top quartile having approximately half the odds of breast cancer of those in the bottom one (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.33, 1.00) but with no reductions in the odds for women in the second and third quartiles. The ORs for second, third and highest quartiles of total lignan intake compared to the lowest were 0.78 (95% CI 0.48, 1.26), 0.74 (0.46, 1.19) and 0.66 (0.41, 1.07), respectively, again with moderate evidence of a linear dose-effect response (p-value for trend 0.09). Further adjustment for non-startch polysaccharides (NSP) intake slightly weakened the phyto-oestrogens-breast cancer associations. CONCLUSIONS: These findings are consistent with the possibility that high phyto-oestrogen intake may protect against breast cancer, but further research is required to confirm this hypothesis.

Adult↗
PubMed2004

An assessment of a variant of the DNA repair gene XRCC3 as a possible nevus or melanoma susceptibility genotype.

Inheritance of the T allele in exon 7 (position 18067) of the DNA repair gene XRCC3 has been reported to be associated with susceptibility to melanoma in a study from Oxford. We report a study in which an attempt was made to confirm this association in a similar population. The most potent risk factor for melanoma in the general population is a phenotype characterized by the presence of multiple melanocytic nevi: the atypical mole syndrome. Our hypothesis is that the atypical mole syndrome may be a marker of genetic susceptibility to melanoma. We have therefore investigated whether the XRCC3 polymorphism influences the nevus phenotype. The XRCC3 genotype was investigated using PCR in a general-practice-based sample of 565 women and 475 patients from a cohort enriched for the atypical mole syndrome, of whom 140 had had melanoma. Allele frequencies were the same in the healthy women, the melanoma cases from this study, and the melanoma cases reported in the Oxford study, but were different from those in the Oxford control group. We found no evidence therefore that the T allele of this XRCC3 polymorphism is indicative of susceptibility to melanoma. There was a marginal relationship with nevus phenotype, but this was no longer statistically significant in multivariate analysis. The previous association between XRCC3 and melanoma may be a result of the choice of control group and we emphasize the need for appropriate choice of controls.

Adult↗
PubMed2003

Mortality after radiological investigation with radioactive Thorotrast: a follow-up study of up to fifty years in Portugal.

Cerebral angiography using a radioactive radiological contrast medium, Thorotrast, was pioneered by Moniz in Portugal in the 1920s. Thorotrast is retained by the reticuloendothelial system, with a biological half-life of several hundred years, so that such patients suffer lifetime exposure to internal radiation. We studied mortality in Portuguese patients who were administered Thorotrast during the period 1928-1959 and in a comparison group of patients who received nonradioactive contrast agents. There were 1096 systemically exposed, 1014 unexposed, and, unique to the Portuguese study, 240 locally exposed Thorotrast patients who were successfully traced and followed up to the end of 1996. Mortality was significantly raised among systemically exposed Thorotrast patients relative to those unexposed for all causes [relative risk (RR) = 2.63], all neoplasms (RR = 6.72), liver cancer (RR = 42.4), chronic liver disease (RR = 5.12), other non-neoplastic diseases of the digestive system (RR = 4.87), neoplastic (RR = 21.9) and non-neoplastic hematological disorders (RR = 6.00), and non-neoplastic diseases of the respiratory system (RR = 4.31). Risks for most of these conditions increased significantly with time since first administration of the contrast medium and with cumulative alpha-particle radiation dose. Mortality was also significantly raised for non-neoplastic disorders of the nervous system (RR = 12.7) and ill-defined conditions (RR = 3.74), but these associations are likely to reflect the initial diagnosis, not Thorotrast exposure, because risks declined significantly with time and/or dose. There were no significant excess deaths from oropharyngeal or nasal cancers, or from any other cause, among patients exposed to Thorotrast locally for visualization of the perinasal sinuses, and no clear trend in risk with time since exposure. This study shows an association between systemic, but not local, exposure to Thorotrast and mortality from liver cancer, chronic liver disease, and neoplastic and non-neoplastic hematological disorders, with risks for these conditions remaining high for over 40 years after administration. Liver conditions, but not hematological disorders, showed a strong and consistent gradient with cumulative alpha-particle radiation dose.

Adolescent↗
PubMed2002

Determinants of the availability and accuracy of self-reported birth weight in middle-aged and elderly women.

Associations have been found between birth weight and many diseases in adult life. In most countries, few birth records exist for older adults; therefore, birth weight is usually obtained by maternal recall or self-report. This study examined determinants of the availability and accuracy of self-report in middle-aged and elderly women. Birth weights, recorded at the time of birth, were found in 1999 for a subset of 363 women participating in a long-running cancer research study in the United Kingdom. Questionnaires were sent to the surviving 286 women requesting information on their birth weight and other factors related to their birth family. Twenty-five percent of the 244 respondents were able to report their birth weight to within 4 ounces (113.4 g) of that listed in birth records, 28% reported it inaccurately, and 47% did not know their birth weight. The most important factors determining the availability of self-reported birth weight were having a living mother and a low birth weight (< or = 6 pounds (2,722 g)). The most important determinants of accuracy, for those who provided a report, were being younger and the eldest child. Research studies relying on self-reported birth weight should take these factors into account.

Adult↗
PubMed2002

Prenatal factors, childhood growth trajectories and age at menarche.

BACKGROUND: In recent studies a larger birth size has been shown to delay the timing of menarche. The mechanisms underlying this association are not clear, however, as birthweight is a predictor of body size in childhood, and a large body size is known to be associated with an early onset of menarche. METHODS: Data from a representative British cohort of 2547 girls born in 1946 who were followed prospectively throughout childhood were used. Information was available on prenatal characteristics, birthweight, height, weight and social circumstances during childhood, and on age at menarche. Random coefficients models were used to estimate the individual trajectories in height and body mass index (BMI) up to age 7 years. The parameters identified by these models were then included in Weibull survival models for the timing of menarche together with birthweight. RESULTS: Birthweight was found to positively influence height and BMI values at age 2 years, but not to affect their rates of change from age 2 to 7 years. Initial analyses showed low birthweight to be associated with an early onset of menarche, but after controlling for growth in infancy this effect was reversed, with girls who were heavy at birth reaching menarche earlier than others with similar infant growth. Rapid growth in infancy was also related to early pubertal maturation. The effects of birthweight and infant growth disappeared, however, when further controlled for growth from age 2 to 7 years. CONCLUSIONS: The effects of birthweight and growth in infancy on the timing of menarche seem to be mediated through growth in early childhood. These findings are consistent with the possibility that timing of menarche may be set in utero or early in life, although it may be modified by changes in body size and composition in childhood.

Birth Weight↗
PubMedDate not supplied

Interaction between CHEK2*1100delC and other low-penetrance breast-cancer susceptibility genes: a familial study.

BACKGROUND: The allele CHEK2*1100delC doubles the risk of breast cancer in unselected women, but could confer a greater risk in women with a family history of the disease, particularly of bilateral breast cancer. Our aim was to measure the risk of breast cancer in relatives of women with bilateral breast cancer who were carriers of this allele. METHODS: A population-based series of 469 bilateral breast cancer cases ascertained through English cancer registries were genotyped for CHEK2*1100delC. Standardised incidence ratios (SIRs) and cumulative risks were calculated for breast cancer, prostate cancer, and all other cancers in the first-degree relatives of carriers and non-carriers. FINDINGS: The relatives of bilateral cases who were wild-type for CHEK2 had three times the population risk of female breast cancer (145 cases: SIR 3.48 (95% CI 2.96-4.09), twice the risk of prostate cancer (34 cases: SIR 2.41, 1.67-3.36) and a large excess of male breast cancer (five cases: SIR 15.06, 4.92-35.36). Relatives of those who were carriers of CHEK2*1100delC had a substantially higher risk of breast cancer (eight cases: SIR 12.11, 5.23-23.88) and possibly prostate cancer (two cases: SIR 9.87, 1.20-35.67). INTERPRETATION: These data suggest a multiplicative interaction between CHEK2*1100delC and other unknown susceptibility genes. In women with a family history of bilateral disease, CHEK2*1100delC confers a high lifetime risk and might be useful for predictive testing. Bilateral breast cancer cases and their families are likely to provide an efficient basis for identification of additional low-penetrance breast-cancer genes.

Adult↗