Xiao-Ou Shu

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (348)2298.97 Total impact

  • Mitchell J Machiela, Chao Agnes Hsiung, Xiao-Ou Shu, Wei Jie Seow, Zhaoming Wang, Keitaro Matsuo, Yun-Chul Hong, Adeline Seow, Chen Wu, H Dean Hosgood, [......], Yi-Long Wu, Pan-Chyr Yang, Baosen Zhou, Min-Ho Shin, Joseph F Fraumeni Jr, Wei Zheng, Dongxin Lin, Stephen J Chanock, Nathaniel Rothman, Qing Lan
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    ABSTRACT: Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of 7 telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of 7 telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI=1.34-1.69) for upper vs. lower quartile of the weighted GRS, P-value=4.54 × 10(-14) ) even after removing rs2736100 (P-value=4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk. This article is protected by copyright. All rights reserved. © 2014 UICC.
    International Journal of Cancer 12/2014; · 6.20 Impact Factor
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    ABSTRACT: We evaluated the association of dietary glycemic index (GI) and glycemic load (GL) with the risk of endometrial cancer in a population-based, case-control study of 1199 endometrial cancer patients and 1212 age-frequency-matched controls in urban Shanghai, China, where diets are typically high in carbohydrates and have a high GL. Information on dietary habits, physical activity, and other relevant information was collected using a validated questionnaire, and anthropometric measurements were taken. Logistic regression was applied in the analysis. Dietary GI and GL were independently associated with risk for endometrial cancer but carbohydrate intake was unrelated to risk. Multivariable-adjusted odds ratios (ORs) for increasing quartiles of intake were 1.0, 1.3, 1.4, and 2.2 [95% confidence interval (CI): 1.2-4.0] for dietary GL (Ptrend = 0.02) and 1.0, 1.2, 1.4, and 1.4 (95% CI: 1.0-2.0) for dietary GI (Ptrend = 0.02). High intake of staples, especially rice, was positively associated with endometrial cancer. The association with GI was more evident among lean and normal weight women, although the test for interaction was not significant. This study suggests that intake of high GL or GI foods, but not carbohydrates per se, may increase risk for endometrial cancer.
    Nutrition and Cancer 12/2014; · 2.70 Impact Factor
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    ABSTRACT: Background Causes of racial disparities in breast cancer incidence and mortality between white and African-American women remain unclear. We evaluated associations of menstrual and reproductive factors with breast cancer risk by race and cancer subtypes. Patients and Methods Included in the study were 1,866 breast cancer cases and 2,306 controls recruited in the Nashville Breast Health Study, a population-based case-control study. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results African-American women were more likely to have estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and triple-negative (ER-PR-Her2-) breast cancer than white women. Age at menarche (≥ 14 years) and multiparity (≥ 3 live births) were inversely associated with (ER+) tumors only, while late age at first live birth (>30 years) and nulliparity were associated with elevated risk; such associations were predominantly seen in whites (OR = 0.70, 95% CI = 0.55-0.88; OR = 0.72, 95% CI = 0.56-0.92; OR = 1.42, 95% CI = 1.13-1.79; OR = 1.32, 95% CI = 1.06-1.63, respectively). Age at menopause between 47 and 51 years was associated with elevated risk of ER- tumors in both whites and African Americans. Among women who had natural menopause, positive association between ever-use of hormone replacement therapy and breast cancer risk was seen in whites only (OR = 1.39, 95% CI = 1.03-1.87). Conclusion Our study suggests that certain hormone-related factors are differentially associated with risk of breast cancer subtypes, and these associations also differ by race.
    Clinical Breast Cancer 12/2014; · 2.42 Impact Factor
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    ABSTRACT: Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93,926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P<5¡Á10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, ten are commonly distributed (MAF>5%) in Europeans, with comparable frequencies with in Asians; and seven SNPs are with low frequency (MAF<5%) in Europeans. In addition, our data suggest that novel biological pathway, such as the protein tyrosine phosphatase (PTP) family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human Molecular Genetics 11/2014; · 7.69 Impact Factor
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    ABSTRACT: We conducted a study of women recruited at Meharry Medical College, a historically black medical school, to investigate the relationship between diabetes and mammographic breast density. A total of 476 women completed in-person interviews, body measurements, and full-field digital mammograms on a Hologic mammography unit from December 2011 to February 2014. Average percent breast density for the left and right breasts combined was estimated using Quantra, an automated algorithm for volumetric assessment of breast tissue. The prevalence of type 2 diabetes was determined by self-report. After adjustment for confounding variables, the mean percent breast density among premenopausal women with type 2 diabetes [[Formula: see text] 13.8 %, 95 % confidence interval (CI) 11.6-15.9] was nonsignificantly lower than that of women without type 2 diabetes ([Formula: see text] 15.9 %, 95 % CI 15.0-16.8) (p = 0.07); however, there was no association among postmenopausal women. The effect of type 2 diabetes in severely obese women (BMI ≥ 35) appeared to differ by menopausal status with a reduction in mean percent breast density in premenopausal women, but an increase in mean percent breast density in postmenopausal women which could have been due to chance. Confirmation of our findings in larger studies may assist in clarifying the role of the insulin signaling breast cancer pathway in women with high breast density.
    Cancer causes & control : CCC. 11/2014;
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    ABSTRACT: Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1,184 genotyped and imputed SNPs in 6,608 Caucasian cases and 37,925 controls, and 895 Asian cases and 1,968 controls, revealed the best signal of association for SNP rs11263763 (P=8.4×10(-14), OR=0.86, 95% CI=0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumour samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high to moderate LD as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.
    Human Molecular Genetics 11/2014; · 7.69 Impact Factor
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    ABSTRACT: Choline deficiency has been shown to induce liver fat accumulation in both rodent and human studies. However, it is unclear whether dietary choline intake is related to fatty liver in the general population.
    The Journal of nutrition. 10/2014;
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    ABSTRACT: Background: We previously reported that higher levels of mitochondrial DNA copy number (mtDNA CN) were associated with lung cancer risk among male heavy smokers (i.e., ≥20 cigarettes per day) in the Alpha-Tocopherol Beta-Carotene (ATBC) study. Here, we present two additional prospective investigations nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and the Shanghai Women's Health Study (SWHS), and pooled with previously published data from ATBC. Materials and Methods: All DNA was extracted from peripheral whole blood samples using the phenol-chloroform method, and mtDNA CN was assayed by fluorescence-based quantitative polymerase chain reaction. Multivariate unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association of mtDNA CN and lung cancer risk. Results: Overall, mtDNA CN was not associated with lung cancer risk in the PLCO, SWHS, or pooled populations (all P-trends > 0.42, P-heterogeneity = 0.0001), and mtDNA CN was inversely associated with lung cancer risk among male smokers in PLCO, the opposite direction observed in ATBC. Additionally, the mtDNA CN association observed among male heavy smokers in ATBC was the opposite direction in PLCO. Conclusion: mtDNA CN was not consistently associated with lung cancer risk across three prospective study populations from Europe, Asia, and the US. Impact: This pooled study suggests no consistent association between pre-diagnostic mtDNA CN levels and lung cancer risk across several populations.
    10/2014;
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    ABSTRACT: Triple-negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. Dual specificity phosphatase 4 (DUSP4) has recently been suggested as a potential marker of chemotherapy resistance for TNBC. DUSP4 gene expression levels were measured in breast cancer tissue from 469 TNBC patients aged 20-75 years who participated in the Shanghai Breast Cancer Survival Study, and their association with recurrence/breast cancer mortality and total mortality was evaluated. Information on breast cancer diagnosis, treatment, and disease progression was collected via medical chart review and multiple in-person follow-up surveys. A Cox regression model was applied in the data analyses. Over a median follow-up of 5.3 years (range: 0.7-8.9 years), 100 deaths and 92 recurrences/breast cancer deaths were documented. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of the DUSP4 gene were studied and were highly correlated (r = 0.76). Low DUSP4 expression levels, particularly of variant 1, were associated with both increased recurrence/breast cancer mortality and increased overall mortality. Hazard ratios with adjustment for age at diagnosis and TNM stage associated with below versus above the median expression level were 1.97 (95 % confidence interval (CI): 1.27-3.05) for recurrence/breast cancer mortality and 2.09 (95 % CI: 1.38-3.17) for overall mortality. Additional adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, and grade did not materially alter the observed associations. Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors.
    Breast Cancer Research and Treatment 10/2014; · 4.47 Impact Factor
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    ABSTRACT: GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.
    Nat Commun. 09/2014;
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    ABSTRACT: Background. Levels of the cyclooxygenase 2 (COX-2) enzyme are elevated in breast cancer tissue, and most COX-2 effects are believed to be mediated through overproduction of prostaglandin-E2 (PGE2). We evaluated associations between the primary urinary metabolite of PGE2 (PGE-M) and breast cancer risk. Methods. A nested case-control study of 504 cases and 1,082 controls was conducted using data from the Shanghai Women's Health Study, a large population-based prospective cohort study of 74,941 Chinese women. Urinary PGE-M was measured using a liquid chromatography/tandem mass spectrometric method. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI), with adjustment for potential confounders. Results. Overall, no association between urinary PGE-M and breast cancer was detected. However, a suggestive positive association was found among postmenopausal women. In particular, a clear dose-response relationship between urinary PGE-M and breast cancer was observed among postmenopausal women with a BMI<25 kg/m2 (P for linear trend = 0.005). Among these women, risk of breast cancer increased from 1.00 (reference) to 1.06 (95% CI: 0.56-1.99), 1.50 (95% CI: 0.79-2.83), and 2.32 (95% CI: 1.24-4.41) for the lowest to highest quartiles of PGE-M, and such associations were stronger among those who were diagnosed with cancer within the first 4 years of sample collection. No apparent association was observed among overweight postmenopausal women (BMI≥25 kg/m2). Conclusion. High urinary PGE-M level was associated with elevated risk of breast cancer among normal weight, postmenopausal women. Impact. Urinary PGE-M level may be useful for breast cancer risk assessment among normal weight, postmenopausal women.
    09/2014;
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    ABSTRACT: Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single nucleotide polymorphisms (SNPs) spanning a 1Mb region around CASP8 were genotyped in 46,450 breast cancer cases and 42,600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1,232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10,052 case and 12,575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% CI)] for the minor allele of 1.05 (1.03-1.07), p=1x10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (p=3 x10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), p=1x10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.
    Human Molecular Genetics 08/2014; · 7.69 Impact Factor
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    ABSTRACT: Background: Mitochondria play an important role in cellular energy metabolism, free radical production, and apoptosis and thus may be involved in cancer development. Methods: We evaluated mtDNA copy number in peripheral leukocytes in relation to CRC risk in a case-control study of 444 CRC cases and 1,423 controls nested in the Shanghai Women's Health Study, a population-based, prospective cohort study. Relative mtDNA copy number was determined by a quantitative real-time PCR assay using peripheral leukocyte DNA samples collected at the time of study enrollment, prior to cancer diagnosis. Results: We found that baseline mtDNA copy number was lower among women who subsequently developed CRC (geometric mean = 0.277, 95% CI: 0.269-0.285) than among women who remained cancer-free (geometric mean = 0.288, 95% CI: 0.284-0.293; P=0.0153). Multivariate adjusted odds ratios (ORs) were 1.26 (95% CI: 0.93-1.70) and 1.44 (95% CI: 1.06-1.94) for the middle and lower tertiles of mtDNA copy number, respectively, compared with the upper tertile (highest mtDNA copy number; P for trend=0.0204). The association varied little by the interval between blood collection and cancer diagnosis. Conclusions: Our data suggest that mtDNA copy number measured in peripheral leukocytes may be a potential biomarker useful for CRC risk assessment. Impact: If confirmed, mtDNA copy number measured in peripheral leukocytes may be a biomarker useful for colorectal cancer risk assessment.
    08/2014;
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    ABSTRACT: We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
    Nature genetics. 08/2014;
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    ABSTRACT: To assess correlations between cruciferous vegetable intake and urinary isothiocyanate (ITC) level, in addition to glutathione S-transferase (GST) genotypes and other individual factors.
    Public Health Nutrition 08/2014; · 2.25 Impact Factor
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    ABSTRACT: We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
    Nature genetics. 08/2014;
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    ABSTRACT: Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10-94<P<5×10-8, odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2×10-23 < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.
    PLoS Genetics 08/2014; 10(8):e1004517. · 8.52 Impact Factor
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    ABSTRACT: Experimental studies have provided evidence that isothiocyanates (ITCs) from cruciferous vegetables may modulate carcinogen metabolism and facilitate carcinogen detoxification and reduce cancer risk. However, no epidemiological studies on liver cancer were reported. This study investigates the association between urinary ITCs levels and liver cancer risk among men and women in Shanghai, China. A nested case-control study of 217 incident cases of liver cancer and 427 matched controls identified from the Shanghai Women's Health Study and Shanghai Men's Health Study was conducted. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) summarizing the association between urinary ITCs levels and liver cancer risk. Compared to those with undetectable ITCs, nonsignificantly inverse association was observed among detectable (OR = 0.80; 95% CI = 0.51-1.26), below-median (OR = 0.76; 95% CI = 0.47-1.24), and above-median concentration (OR = 0.86; 95% CI = 0.52-1.41) with liver cancer risk. Similar patterns were observed when urinary ITCs levels were categorized into tertiles or quartiles. Although our study firstly focused on the association between urinary ITCs exposure and liver cancer risk, we did not find significant results. Future multicenter prospective, different population studies are warranted to validate our findings.
    Nutrition and Cancer 07/2014; · 2.70 Impact Factor
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    ABSTRACT: In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,8 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4950 at q32. (in intron 2 of the ZC3H11A gene; P = 8.82 × 0 −9), rs0474352 at 5q4.3 (near the ARRDC3 gene; P = .67 × 0 −9) and rs2290203 at 5q26. (in intron 4 of the PRC1 gene; P = 4.25 × 0 −8). We replicated these associations in 6,003 cases and 4,335 controls of European ancestry (P = 0.030, 0.004 and 0.00, respectively). Data from the ENCODE Project suggest that variants rs4950 and rs0474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer. Breast cancer is one of the most common malignancies among women worldwide. Genetic factors have a substantial role in breast cancer etiology 1,2 . Thus far, genome-wide association studies (GWAS) have identified approximately 75 genetic loci associated with breast cancer risk 2–5 . With the exception of the studies we have conducted among East Asian women 6–9 and one study conducted among women of African ancestry 10 , all other published GWAS have been conducted among women of European ancestry. Genetic risk variants identified thus far from GWAS explain only about 10% of familial risk for breast cancer in East Asian women 3 . Given the dif-ferences in genetic architecture and environmental exposures for women of European and East Asian ancestry, additional GWAS need to be conducted among East Asian women to study the genetic basis of breast cancer risk. The current study was conducted as part of the Asia Breast Cancer Consortium (ABCC) to search for additional susceptibility loci for breast cancer. Included in this study are data obtained from 22,780 breast cancer cases and 24,181 controls who were recruited in 14 studies conducted in multiple Asian countries (Supplementary Table 1). The discovery stage (stage 1) included 2 GWAS in which 5,285 Chinese women (SBCGS-1) and 4,777 Korean women (SeBCS1) were scanned primarily using Affymetrix Genome-Wide Human SNP Array 6.0, which consists of 906,602 SNPs. After applying quality control filters described previously 6,9,11 , 5,152 Chinese women (2,867 cases and 2,285 controls; 677,157 SNPs) and 4,298 Korean women (2,246 cases and 2,052 controls; 555,117 SNPs) remained in the cur-rent analysis. Imputation was conducted for each study following the MACH algorithm 12 using HapMap 2 release 22 CHB (Han Chinese in Beijing, China) and JPT (Japanese in Tokyo, Japan) data (2,416,663 SNPs) as the reference. Only SNPs with a high imputation quality score (RSQR ≥ 0.50) were analyzed for associations with breast can-cer risk. In the analyses of data from Chinese and Korean women, a total of 1,930,412 and 1,907,146 SNPs, respectively, were included. A meta-analysis of these GWAS data was conducted using a fixed-effects, inverse variance meta-analysis with the METAL program 13 . There was little evidence of inflation in the association test statis-tics for the studies included in stage 1 (genomic inflation factors (λ): λ = 1.0426 for SBCGS-1, λ = 1.0431 for SeBCS1 and λ = 1.0499 for both studies combined; Supplementary Fig. 1). When scaled to a study of 1,000 cases and 1,000 controls, λ 1,000 values were 1.02, 1.02 and 1.01, respectively. To select SNPs for stage 2 replication, we used the following criteria: (i) association P < 0.05 in the stage 1 meta-analysis results; (ii) the
    Nature Genetics 07/2014; · 35.21 Impact Factor
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    ABSTRACT: Cognitive decline is a common health problem among breast cancer patients and understanding trajectories of cognitive change following among breast cancer survivors is an important public health goal. We conducted a longitudinal study to investigate the cognitive function changes from 18 month to 3 years after breast cancer diagnosis among participants of the Shanghai Breast cancer survivor study, a population-based cohort study of breast cancer survivors. In our study, we completed cognitive function evaluation for 1,300 breast cancer survivors at the 18th month's survey and 1,059 at 36th month's survey, respectively, using a battery of cognitive function measurements. We found the scores in attention and executive function, immediate memory and delayed memory significantly improved from 18 to 36 months after breast cancer diagnosis. The improvements appeared in breast cancer survivors receiving treatments (i.e., surgery, radiotherapy, tamoxifen, or chemotherapy combined with or without tamoxifen), but not in those who received neither chemotherapy nor tamoxifen treatment. The results indicate that cognitive functions, particularly immediate verbal episodic memory, and delayed memory significantly improved among breast cancer survivors from 18 to 36 months after cancer diagnosis. In general, comorbidity was inversely associated with the improvements.
    Breast Cancer Research and Treatment 07/2014; · 4.47 Impact Factor

Publication Stats

7k Citations
2,298.97 Total Impact Points

Institutions

  • 2012–2014
    • University of Texas MD Anderson Cancer Center
      • Division of Cancer Prevention & Population Sciences
      Houston, Texas, United States
  • 2001–2014
    • Vanderbilt University
      • • Division of Epidemiology
      • • Vanderbilt Epidemiology Center
      • • Department of Medicine
      • • Vanderbilt-Ingram Cancer Center (VICC)
      Nashville, Michigan, United States
  • 1998–2014
    • Shanghai Cancer Institute
      Shanghai, Shanghai Shi, China
  • 2013
    • Institute of Cancer Research
      Londinium, England, United Kingdom
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, England, United Kingdom
  • 2012–2013
    • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2010–2013
    • Imperial College London
      • • Department of Epidemiology and Biostatistics
      • • Department of Primary Care and Public Health
      London, ENG, United Kingdom
    • Gateway-Vanderbilt Cancer Treatment Center
      Clarksville, Tennessee, United States
    • St. Jude Children's Research Hospital
      • Department of Epidemiology & Cancer Control
      Memphis, TN, United States
    • Mayo Clinic - Rochester
      • Department of Health Science Research
      Rochester, MN, United States
  • 2008–2013
    • Shanghai Municipal Center for Disease Control and Prevention
      Shanghai, Shanghai Shi, China
  • 2011
    • University of Hawaiʻi at Mānoa
      • Office of Public Health Studies
      Honolulu, HI, United States
    • U.S. Food and Drug Administration
      Washington, Washington, D.C., United States
    • Queensland Institute of Medical Research
      Brisbane, Queensland, Australia
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2009–2011
    • Fudan University
      • • School of Public Health
      • • Department of Health Statistics and Social Medicine
      Shanghai, Shanghai Shi, China
    • Northwestern University
      • Department of Preventive Medicine
      Evanston, IL, United States
    • University of Minnesota Twin Cities
      • Department of Pediatrics
      Minneapolis, MN, United States
  • 2004–2011
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Occupational and Environmental Epidemiology
      Bethesda, MD, United States
  • 2007–2009
    • National Institutes of Health
      • • Division of Cancer Epidemiology and Genetics
      • • Branch of Occupational and Environmental Epidemiology
      Bethesda, MD, United States
    • Harvard University
      • Department of Epidemiology
      Boston, MA, United States
  • 2002–2008
    • Yale University
      New Haven, Connecticut, United States
  • 2005–2007
    • Meharry Medical College
      • Department of Surgery
      Nashville, Tennessee, United States
  • 2003
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
    • Wake Forest School of Medicine
      • Center for Cancer Genomics
      Winston-Salem, NC, United States
  • 2000
    • University of South Carolina
      • Department of Epidemiology & Biostatistics
      Columbia, SC, United States