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Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant. Analyses integrating functional genomics data identified 195 putative susceptibility genes, enriched in PI3K/AKT, TNF/NF-κB, p53 and Wnt/β-catenin pathways. Single-cell RNA sequencing or in vitro experiment data provided additional functional evidence for 105 genes. Our study uncovered large numbers of association signals and candidate susceptibility genes for breast cancer, uncovered breast cancer genetics and biology, and supported the value of including multi-ancestry data in fine-mapping analyses.

Supplemental Digital Content is Available in the Text.Using 4-year longitudinal data, the authors observed that highly myopic individuals with eye shape deformity had myopic maculopathy progression more frequently than those with nondeformed eye shape. Eye shape deformity identified from three-dimensional magnetic resonance imaging is a novel predictor for myopic maculopathy progression, equally as important as axial length.

Alcohol intake can alter gut microbiome, which may subsequently affect human health. However, limited population-based, prospective studies have investigated associations of habitual and recent alcohol intake with the gut microbiome, particularly among Black/African American individuals.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P< 5 × 10−8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

IMPORTANCE: Individuals with high myopia younger than 18 years are at relatively high risk of progressively worsening myopic maculopathy. Additional studies are needed to investigate the progression of myopic maculopathy in this age group, as well as the risk factors associated with progression. OBJECTIVE: To investigate the 4-year progression of myopic maculopathy in children and adolescents with high myopia, and to explore potential risk factors. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based observational study with 4-year follow-up included a total of 548 high myopic eyes (spherical power −6.00 or less diopters) of 274 participants aged 7 to 17 years. Participants underwent comprehensive ophthalmic examination at baseline and 4-year follow-up. Myopic maculopathy was accessed by the International Photographic Classification and Grading System. The data analysis was performed from August 1 to 15, 2023. MAIN OUTCOMES AND MEASURES: The progression of myopic maculopathy progression over 4 years and associated risk factors. RESULTS: The 4-year progression of myopic maculopathy was found in 67 of 548 eyes (12.2%) of 274 participants (138 girls [50.4%] at baseline and 4-year follow-up) with 88 lesion changes, including new signs of the tessellated fundus in 16 eyes (18.2%), diffuse atrophy in 12 eyes (13.6%), patchy atrophy in 2 eyes (2.3%), lacquer cracks in 9 eyes (10.2%), and enlargement of diffuse atrophy in 49 eyes (55.7%). By multivariable analysis, worse best-corrected visual acuity (odds ratio [OR], 6.68; 95% CI, 1.15-38.99; P = .04), longer axial length (AL) (OR, 1.73; 95% CI, 1.34-2.24; P &lt; .001), faster AL elongation (OR, 302.83; 95% CI, 28.61-3205.64; P &lt; .001), and more severe myopic maculopathy (diffuse atrophy; OR, 4.52; 95% CI, 1.98-10.30; P &lt; .001 and patchy atrophy; OR, 3.82; 95% CI, 1.66-8.80; P = .002) were associated with myopic maculopathy progression. CONCLUSIONS AND RELEVANCE: In this observational study, the progression of myopic maculopathy was observed in approximately 12% of pediatric high myopes for 4 years. The major type of progression was the enlargement of diffuse atrophy. Risk factors for myopic maculopathy progression were worse best-corrected visual acuity, longer AL, faster AL elongation, and more severe myopic maculopathy. These findings support consideration of follow-up in these individuals and trying to identify those at higher risk for progression.

There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality.

IMPORTANCE: Understanding the long-term axial elongation trajectory in high myopia is important to prevent blindness. OBJECTIVE: To evaluate axial elongation trajectories and related visual outcomes in children and adults with high myopia. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, participants in the Zhongshan Ophthalmic Centre–Brien Holden Vision Institute high myopia cohort were followed up every other year for 8 years. Participants with axial length measurements at baseline (2011 or 2012) and at least 1 follow-up visit were included. Participants were grouped according to baseline age as children and adolescents (7 to &lt;18 years), young adults (18 to &lt;40 years), and older adults (≥40 to 70 years). Data were analyzed from November 1, 2022, to June 1, 2023. EXPOSURE: High myopia (spherical power ≤−6.00 diopters). MAIN OUTCOMES AND MEASURES: Longitudinal axial elongation trajectories were identified by cluster analysis. Axial elongation rates were calculated by linear mixed-effects models. A 2-sided P &lt; .05 was defined as statistically significant. RESULTS: A total of 793 participants (median [range] age, 17.8 [6.8-69.7] years; 418 females [52.7%]) and 1586 eyes were included in the analyses. Mean axial elongation rates were 0.46 mm/y (95% CI, 0.44-0.48 mm/y) for children and adolescents, 0.07 mm/y (95% CI, 0.06-0.09 mm/y) for young adults, and 0.13 mm/y (95% CI, 0.07-0.19 mm/y) for older adults. Cluster analysis identified 3 axial elongation trajectories, with the stable, moderate, and rapid progression trajectories having mean axial elongation rates of 0.02 mm/y (95% CI, 0.01-0.02 mm/y), 0.12 mm/y (95% CI, 0.11-0.13 mm/y), and 0.38 mm/y (95% CI, 0.35-0.42 mm/y), respectively. At 8 years of follow-up, compared with the stable progression trajectory, the rapid progression trajectory was associated with a 6.92 times higher risk of developing pathological myopic macular degeneration (defined as diffuse or patchy chorioretinal atrophy or macular atrophy; odds ratio, 6.92 [95% CI, 1.07-44.60]; P = .04), and it was associated with a 0.032 logMAR decrease in best-corrected visual acuity (β = 0.032 [95% CI, 0.001-0.063]; P = .04). CONCLUSIONS AND RELEVANCE: The findings of this 8-year follow-up study suggest that axial length in high myopia continues to increase from childhood to late adulthood following 3 distinct trajectories. At 8 years of follow-up, the rapid progression trajectory was associated with a higher risk of developing pathological myopic macular degeneration and poorer best-corrected visual acuity compared with the stable progression trajectory. These distinct axial elongation trajectories could prove valuable for early identification and intervention for high-risk individuals.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint< 5 × 10−8), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (Pint< 5 × 10−8). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (Pint= 2 × 10−6). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1and RGL3/ELAVL3previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (Pint< 10−3). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep–wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

BackgroundThe aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted.MethodsWe conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women’s Health Study and Shanghai Men’s Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis.ResultsOur study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10−8. These DMPs were identified as cg09198866 (MYH9; TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34).ConclusionsWhile replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P< 5 × 10−8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66–7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

Ginseng has been commonly used in Asian countries to promote longevity and health for >2000 years. Recent in vitro and in vivo studies, coupled with limited epidemiologic studies, have suggested that regular ginseng consumption may be related to lower cancer risk.

We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the EGFRgene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared with EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (odds ratio = 8.63, 95% confidence interval: 5.67–13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (odds ratio = 3.50, 95% confidence interval: 2.44–5.00) (p-heterogeneity = 3.66 × 10−3). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.

Largemouth bass (Micropterus salmoides) is poor at utilizing starch, and it is not clear whether commensal microorganisms can alleviate the adverse influences of high wheat starch in M. salmoides.Here, twelve autochthonous microorganisms with amylase producing abilities were isolated from the M. salmoidesfed with diets containing 6 %, 12 %, or 18 % starch. Among them, Citrobacter freundiiF1, Bacillus altitudinisF7, Enterococcus casseliflavusD12, Plesiomonas shigelloidesD15, Bacillus cabrialesiiD16, Citrobacter portucalensisK25 and Serratia oryzaeK28 showed no hemolytic activity and were safety for M. salmoides. A 42-d feeding experiment was performed to study the functions of the seven microorganisms. A total of 810 fish (5.9 ± 0.01 g) were equally distributed into 9 groups. The control groups C6 and C18 were respectively fed with 6 % and 18 % wheat starch diets, the groups F1, F7, D12, D15, D16, K25 and K28 were fed with 18 % wheat starch diets respectively supplemented with 1.0×108CFU/g C. freundiiF1, B. altitudinisF7, E. casseliflavusD12, P. shigelloidesD15, B. cabrialesiiD16, C. portucalensisK25 and S. oryzaeK28. The results indicated that compared with 6 % starch, 18 % level inhibited the growth performance, increased the hepatic glycogen and fat contents, improved the activities of glycolysis-related enzymes (hexokinase (HK), glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK)), decreased the activities of gluconeogenesis-related enzymes, pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK), promoted the activity of lipid synthases-related enzyme carnitine palmitoyl transferaseⅠ (CPT1) and reduced the activity of lipolytic enzymes-related lipoprotein lipase (LPL). C. freundiiF1, P. shigelloidesD15, C. portucalensisK25 and S. oryzaeK28 had relatively poor alleviating effects, while B. altitudinisF7, E. casseliflavusD12 and B. cabrialesiiD16 significantly promoted the final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), decreased feed conversion rate (FCR), significantly reduced the hepatic glycogen and fat contents, decreased the activities of glycolysis-related enzymes (HK, GK, PK), improved the activities of gluconeogenesis-related enzymes (PC, PEPCK), reduced the activity of lipid synthases-related enzyme CPT1 (P< 0.05), which proved that these three strains could effectively alleviate the negative effects of high starch in M. salmoides. In conclusion, among the seven autochthonous microorganisms, B. altitudinisF7, E. casseliflavusD12 and B. cabrialesiiD16 presented better potential advantages in improving glucose and lipid metabolisms, thus promoting the growth performance of M. salmoidesfed with high wheat starch diet.

Animal and small-cohort human studies have shown that tea consumption affects the gut microbiome, but evidence from large cohort studies is lacking.

Purpose: The High-Energy Photon Source (HEPS) is a 6 GeV storage ring-based light source under construction in Beijing, China. Its accelerator consists of a 6 GeV storage ring, a full-energy booster, an S-band normal-conducting 500 MeV linac, and three transport lines. As the beginning of HEPS, a stable linac is quite important, which needs a qualified waveguide distribution system to transmit microwave power from klystrons to accelerating structures. Methods: Installation and high-power conditioning of the HEPS linac were performed from February to September 2022. The assembly and conditioning of the waveguide distribution system were completed in April and July, respectively. The design of the waveguide distribution system began in 2018 and was finalized at the end of 2020 after multiple iterations. Results: Owing to careful design, fabrication, and assembly preparation, the assembly and conditioning of the system proceeded smoothly and considerable time was saved. Conclusion: The entire process from the design to the ultimate realization of the system is introduced in detail in this paper. Satisfactory measurement results were obtained for some waveguide components.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

Background Most of the genetic variants identified from genome-wide association studies of breast cancer have not been validated in Asian women. No risk assessment model that incorporates both genetic and clinical predictors is currently available to predict breast cancer risk in this population. Methods We analyzed 12 single-nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies mostly of women of European ancestry as being associated with the risk of breast cancer in 3039 case patients and 3082 control subjects who participated in the Shanghai Breast Cancer Study. All participants were interviewed in person to obtain information regarding known and suspected risk factors for breast cancer. The c statistic, a measure of discrimination ability with a value ranging from 0.5 (random classification) to 1.0 (perfect classification), was estimated to evaluate the contribution of genetic and established clinical predictors of breast cancer to a newly established risk assessment model for Chinese women. Clinical predictors included in the model were age at menarche, age at first live birth, waist-to-hip ratio, family history of breast cancer, and a previous diagnosis of benign breast disease. The utility of the models in risk stratification was evaluated by estimating the proportion of breast cancer patients in the general population that could be accounted for above a given risk threshold as predicted by the models. All statistical tests were two-sided. Results Eight SNPs (rs2046210, rs1219648, rs3817198, rs8051542, rs3803662, rs889312, rs10941679, and rs13281615), each of which reflected a genetically independent locus, were found to be associated with the risk of breast cancer. A dose-response association was observed between the risk of breast cancer and the genetic risk score, which is an aggregate measure of the effect of these eight SNPs (odds ratio for women in the highest quintile of genetic risk score vs those in the lowest = 1.85, 95% confidence interval = 1.58 to 2.18, [P.sub.trend] = 2.5 x [10.sup.-15]). The genetic risk score, the waist-to-hip ratio, and a previous diagnosis of benign breast disease were the top three predictors of the risk of breast cancer, each contributing statistically significantly (P< .001) to the full risk assessment model. The model, with a c statistic of 0.6295 after adjustment for overfitting, showed promise for stratifying women into different risk groups; women in the top 30% risk group accounted for nearly 50% of the breast cancers diagnosed in the general population. Conclusion A risk assessment model that includes both genetic markers and clinical predictors may be useful to classify Asian women into relevant risk groups for cost-efficient screening and other prevention programs. DOI: 10.1093/jnci/djq170

Background: Soy food is a rich source of isoflavones--a class of phytoestrogens that has both antiestrogenic and anticarcinogenic properties. Objective: The objective was to evaluate the association of adolescent and adult soy food intake with breast cancer risk in a cohort of 73,223 Chinese women who participated in the Shanghai Women's Health Study. Design: A validated food-frequency questionnaire was used to assess usual dietary intake during adulthood and adolescence. After a mean follow-up of 7.4 y, 592 incident cases of breast cancer were identified for longitudinal analyses by using Cox regressions. Results: Adult soy food consumption, measured either by soy protein or isoflavone intake, was inversely associated with the risk of premenopausal breast cancer, and the association was highly statistically significant (P for trend < 0.001). The multivariate-adjusted relative risks (RRs) for the upper intake quintile compared with the lowest quintile were 0.41 (95% CI: 0.25, 0.70) for soy protein intake and 0.44 (95% CI: 0.26, 0.73) for isoflavone intake. High intake of soy foods during adolescence was also associated with a reduced risk of premenopausal breast cancer (RR: 0.57; 95% CI: 0.34, 0.97). Women who consumed a high amount of soy foods consistently during adolescence and adulthood had a substantially reduced risk of breast cancer. No significant association with soy food consumption was found for postmenopausal breast cancer. Conclusion: This large, population-based, prospective cohort study provides strong evidence of a protective effect of soy food intake against premenopausal breast cancer.

Background: Diet plays a key role in the development of type 2 diabetes (T2D), but little is known about the contributions of specific nutrients in populations in which dietary patterns differ from Western populations. Objective: We examined associations between calcium and magnesium intakes and the risk of T2D in a Chinese population. Design: We used data from a population-based, prospective study of 64,191 women who were free of T2D or other chronic diseases at study recruitment and were living in urban Shanghai, China. Dietary intake, physical activity, and anthropometric measurements were assessed through in-person interviews. A Cox regression model was used to evaluate the association of the exposures under study with the risk of T2D. Results: An inverse association between calcium and magnesium intakes and T2D risk was observed. The relative risks for the lowest to the highest quintiles of calcium intake were 1.00, 0.82, 0.73, 0.67, and 0.74 (P for trend < 0.001), and for magnesium they were 1.00, 0.84, 0.84, 0.79, and 0.86 (P for trend < 0.001). Milk intake was also inversely associated with the risk of T2D. Conclusion: Our data suggest that calcium and magnesium intakes may protect against the development of T2D in this population.

Background: Soy and some of its constituents, such as isoflavones, have been shown to have cancer-inhibitory activities in experimental studies. Data from epidemiologic studies linking usual soy food intake with colorectal cancer are limited and inconsistent. Objective: The objective was to investigate whether soy food intake is associated with colorectal cancer risk. Design: We prospectively examined 68,412 women aged 40-70 y and free of cancer and diabetes at enrollment. Usual soy food intake was assessed at baseline (1997-2000) and reassessed during the first follow-up (2000-2002) through in-person interviews with a validated food-frequency questionnaire. We excluded the first year of observation to minimize lifestyle changes related to preclinical disease. Results: During a mean follow-up of 6.4 y, 321 incident colorectal cancer cases were identified. After adjustment for potential confounding factors, total soy food intake was inversely associated with colorectal cancer risk. Each 5-g/d increment in intake of soy foods as assessed by dry weight [equivalent to [approximately equal to]1 oz (28.35 g) tofu/d] was associated with an 8% reduction in risk (95% CI: 3%, 14%). Women in the highest tertile of intake had a multivariate relative risk of 0.67 (95% CI: 0.49, 0.90) compared with those in the lowest tertile (P for trend = 0.008). This inverse association was primarily confined to postmenopausal women. Similar results were also found for intakes of soy protein and isoflavones. Conclusion: This prospective study suggests that consumption of soy foods may reduce the risk of colorectal cancer in postmenopausal women.

Background: Few studies have investigated the association of dietary carbohydrate and fiber intake with breast cancer risk in women in China, where carbohydrate intake is traditionally high. Objective: The objective was to prospectively evaluate the association of dietary carbohydrates, glycemic index, glycemic load, and dietary fiber with breast cancer risk and to determine whether the effect of these dietary intakes is modified by age and selected insulin- or estrogen-related risk factors. Design: A total of 74,942 women aged 40-70 y were recruited into the Shanghai Women's Health Study, a population-based cohort study. Dietary intake was assessed by in-person interviews. A Cox proportional hazards regression model was used to evaluate associations. Results: During an average of 7.35 y of follow-up, 616 incident breast cancer cases were documented. A higher carbohydrate intake was associated with a higher risk of premenopausal breast cancer (P for trend = 0.002). Compared with the lowest quintile, the hazard ratios (and 95% CIs) were 1.47 (1.00, 2.32) and 2.01 (1.26, 3.19) for the fourth and fifth quintiles, respectively. A similar pattern was found for glycemic load. The association between carbohydrate intake and breast cancer was significantly modified by age; the increased breast cancer risk associated with carbohydrate intake was restricted to women who were younger than 50 y. No significant association of breast cancer risk with glycemic index or dietary fiber intake was found. Conclusion: Our data suggest that a high carbohydrate intake and a diet with a high glycemic load may be associated with breast cancer risk in premenopausal women or women < 50 y.

Samples of ultra-high-purity tungsten prepared using chemical vapour deposition (CVD) technique were irradiated with neutrons at temperatures Tirr= 373–483 K (stage II of defect recovery) and Tirr= 573–673 K (stage III) up to 0.15 displacements per atom (dpa) in the Belgian reactor (BR2). The study of the microstructure of neutron-damaged samples using transmission electron microscopy (TEM) revealed visible defects with a predominance of dislocation loops. With an increase in the neutron irradiation temperature, the spatial distribution of the loops acquired pronounced inhomogeneity, and their average size moderately increased. Cavities and voids were not observed. Irradiation-induced hardening was found and a linear correlation was obtained between Vickers microhardness and nanohardness for undamaged and neutron-irradiated CVD-W samples. Irradiation of tungsten with neutrons led to a significant increase in the retention of deuterium, which accumulated mainly in vacancy-type traps. Furthermore, the influence of the columnar grain structure in low-dose neutron-irradiated tungsten seemed to be non-trivial upon deuterium retention.

Background: Cruciferous vegetables are the primary source of isothiocyanates and other glucosinolate derivatives that are known to induce phase II detoxifying enzymes, including glutathione S-transferases (GSTs). Objective: We investigated the independent and combined effects of cruciferous vegetable intake and the GSTP1 [Ile.sup.105]Val genetic polymorphism on breast cancer risk. Design: Analyses included 3035 cases and 3037 population controls who were participating in the Shanghai Breast Cancer Study and for whom diet and genetic data were complete (87% of cases and 85% of controls). Results: With the use of multivariate logistic regression, the GSTP1 Val/Val genotype was significantly associated with greater breast cancer risk (OR = 1.50; 95% CI: 1.12, 1.99). The association was significantly greater in premenopausal women (OR = 1.69; 95% CI: 1.17, 2.43) than in postmenopausal women (OR = 1.20; 95% CI: 0.74, 1.92). Total cruciferous vegetable intake was not significantly associated with breast cancer risk, although subjects reporting greater turnip (P for trend < 0.001) and Chinese cabbage (P for trend = 0.049) intakes had a significantly lower postmenopausal breast cancer risk. Women with the GSTP1 Val/Val genotype and low cruciferous vegetable intake had a breast cancer risk 1.74-fold (95% CI: 1.13, 2.67) that of women with the Ile/Ile or Ile/Val genotype. This effect of low cruciferous vegetable intake and the Val/Val genotype was seen predominantly among premenopausal women (OR = 2.08; 95% CI = 1.20, 3.59). Conclusions: Cruciferous vegetable intake consistent with high isothiocyanate exposure may reduce breast cancer risk. Cruciferous vegetable intake also may ameliorate the effects of the GSTP1 genotype. KEY WORDS Cruciferous vegetables, GSTP1 genetic polymorphism, breast cancer risk, gene-diet combined effect

Background: It has been postulated that a diet high in legumes may be beneficial for the prevention of type 2 diabetes mellitus (type 2 DM). However, data linking type 2 DM risk and legume intake are limited. Objective: The objective of the study was to examine the association between legume and soy food consumption and self-reported type 2 DM. Design: The study was conducted in a population-based prospective cohort of middle-aged Chinese women. We followed 64 227 women with no history of type 2 DM, cancer, or cardiovascular disease at study recruitment for an average of 4.6 y. Participants completed in-person interviews that collected information on diabetes risk factors, including dietary intake and physical activity in adulthood. Anthropometric measurements were taken. Dietary intake was assessed with a validated food-frequency questionnaire at the baseline survey and at the first follow-up survey administered 2-3 y after study recruitment. Results: We observed an inverse association between quintiles of total legume intake and 3 mutually exclusive legume groups (peanuts, soybeans, and other legumes) and type 2 DM incidence. The multivariate-adjusted relative risk of type 2 DM for the upper quintile compared with the lower quintile was 0.62 (95% CI: 0.51,0.74) for total legumes and 0.53 (95% CI: 0.45, 0.62) for soybeans. The association between soy products (other than soy milk) and soy protein consumption (protein derived from soy beans and their products) with type 2 DM was not significant. Conclusions: Consumption of legumes, soybeans in particular, was inversely associated with the risk type 2 DM. KEY WORDS Type 2 diabetes, legume intake, soy intake, middle-aged women, Chinese women, protective factors

Background: Epidemiologic studies have suggested that a high phytoestrogen intake is inversely associated with cardiovascular disease risk factors and the incidence of cardiovascular events. However, the relation between the intake of isoflavone, a major component of phytoestrogen, and vascular endothelial function and the atherosclerotic burden remains unclear. Objective: We aimed to investigate the effects of various dietary soy isoflavone intakes on brachial artery flow-mediated dilation and mean maximum carotid intima-media thickness. Design: We studied 126 consecutive patients ([bar.x] [+ or -] SD age: 66.5 [+ or -] 11.1 y; 69% male) at high risk of cardiovascular events (94% had documented coronary artery disease or stroke; 44% had diabetes). A validated food-frequency questionnaire was used to estimate their dietary intake after they achieved stable dietary patterns for 3 mo. Results: The median intakes of isoflavone and soy protein were 5.5 (range: 2.2-13.3) mg/d and 1.2 (range: 0.4-2.8) g/d, respectively. Persons in the 4th quartile of daily isoflavone intake had significantly (P < 0.05) greater flow-mediated dilation--but not mean maximum carotid intima-media thickness--than did those in the lower quartiles. After adjustment for potential confounders, a higher isoflavone intake in the 4th than in the 1st quartile (> 13.3 rag/d), but not a higher intake of soy protein, predicted an absolute 2.71% increase in flow-mediated dilation (relative increase: 103%; P = 0.02) and a 0.17-mm decrease in mean maximum carotid intima-media thickness (relative decrease: 14.5%; P = 0.04). Conclusion: In persons at high risk of cardiovascular events, a greater isoflavone intake is associated with better vascular endothelial function and lower carotid atherosclerotic burden. KEY WORDS Isoflavone, flow-mediated dilation, carotid intima-media thickness

Background: Several small-scale clinical trials have suggested a potential beneficial effect of short-term soy consumption on blood pressure (BP). Data are scanty on long-term effects of the usual intake of soy foods on BP in general populations. Objective: Our aim was to examine the association between usual intake of soy foods and BP. Design: The usual intake of soy foods was assessed at baseline, and BP was measured 2-3 y after the baseline survey among 45 694 participants of the Shanghai Women's Health Study aged 40-70 y who had no history of hypertension, diabetes, or cardiovascular disease at recruitment. Multiple regression models were used to estimate mean differences in BP associated with various intakes of soy foods. Results: Soy protein intake was inversely associated with both systolic BP (P for trend = 0.01) and diastolic BP (P for trend = 0.009) after adjustment for age, body mass index, and lifestyle and other dietary factors. The adjusted mean systolic BP was 1.9 mm Hg lower (95% CI: -3.0, -0.8 mm Hg) and the diastolic BP was 0.9 mm Hg lower (- 1.6, -0.2 mm Hg) in women who consumed [greater than or equal to] 25 g soy protein/d than in women consuming 60 y old, the corresponding differences were -4.9 mm Hg (95% CI: -8.0, -1.9 mm Hg) for systolic BP and -2.2 mm Hg (95% CI: -3.8, -0.6 mm Hg) for diastolic BP. Conclusion: Usual intake of soy foods was inversely associated with both systolic and diastolic BPs, particularly among elderly women. KEY WORDS Blood pressure, soy foods, women, longitudinal observation

Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.

Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups.

Background: Cigarette smoking has been shown to increase oxidative DNA damage in human sperm cells. Assessment of the role of cigarette smoking in the etiology of childhood cancer has focused primarily on the effect of maternal smoking. Similar studies in relation to paternal smoking, however, have been inconclusive. Few studies have evaluated the effect of paternal smoking in the preconception period, and most of these could not disentangle the effects of paternal from maternal smoking. Purpose: We investigated the relationship of paternal smoking, particularly in the preconception period, with childhood cancer among offspring of the nonsmoking mothers. Methods: We conducted a population-based, case-control study in Shanghai, People's Republic of China, where the prevalence of smoking is high among men but extremely low among women. The study included 642 childhood cancer case patients ([is less than]15 years of age) and their individually matched control subjects. Information concerning parental smoking, alcohol drinking, and other exposures of the index child was obtained by direct interview of both parents of the study subjects. Odds ratios (ORs), derived from conditional logistic regression models, were used to measure the association between paternal smoking and risk of childhood cancers. Results and Conclusions: Paternal preconception smoking was related to a significantly elevated risk of childhood cancers, particularly acute leukemia and lymphoma. The risks rose with increasing pack-years of paternal preconception smoking for acute lymphocytic leukemia (ALL) (P for trend = .01), lymphoma (P for trend = .07), and total cancer (P for trend = .006). Compared with children whose fathers had never smoked cigarettes, children whose fathers smoked more than five pack-years prior to their conception had adjusted ORs of 3.8 (95% confidence interval [CI] = 1.3-12.3) for ALL, 4.5 (95% CI = 1.2-16.8) for lymphoma, 2.7 (95% CI = 0.8-9.9) for brain tumors, and 1.7 (95% CI = 1.2-2.5) for all cancers combined. Statistically significant increased risks of cancer were restricted to children under the age of 5 years at diagnosis or those whose fathers had smoked during all of the 5 years prior to conception. Implications: Further studies are needed to confirm the association of paternal smoking with increased risk of cancer in offspring, to clarify the pattern of risks in relation to the timing of cigarette smoking, and to elucidate the biologic mechanism involved in predisposing the offspring to cancer. For example, it may be that paternal smoking induces prezygotic genetic damage that, in turn, acts as the predisposing factor. [J Natl Cancer Inst 1997;89:238-44]