Family History and Stroke Risk in China: Evidence from a Large Cohort Study

Tian Tian,Guangfu Jin,Canqing Yu,Jun Lv,Yu Guo,Zheng Bian,Ling Yang,Yiping Chen,Hongbing Shen,Zhengming Chen,Zhibin Hu,Liming Li 대한뇌졸중학회 2017 Journal of stroke Vol.19 No.2

Background and Purpose Large cohort studies on relationship between family history of stroke(FHS) and stroke risk are lacking in Asians. We aimed to systematically evaluate the association ofFHS with stroke risk in a cohort study of 0.5 million Chinese adults. Methods Information about FHS was self-reported. The median follow-up time was 7.16 years andthe end-point of follow-up was incident stroke, which was entered directly into the China KadoorieBiobank system. Multivariate analyses were performed with Cox proportional hazards model, andinteraction analyses were carried using likelihood-ratio tests. Results Compared with participants without FHS, the hazard ratio (HR) (95% confidence interval,CI) of stroke for participants with FHS was 1.50 (1.46-1.55). The HRs increased with the number offirst degree relatives with stroke (HRs=1.41, 1.98 and 2.47 for 1, 2 and ≥3 relatives, respectively,Ptrend <0.001). The HRs were 1.57 (95% CI: 1.50-1.66) and 1.49 (95% CI: 1.45-1.54) for siblinghistory and parental history, respectively. Similar associations with offspring stroke risk wereobserved between paternal history (HR=1.48, 95% CI: 1.43-1.54) and maternal history (HR=1.49,95% CI: 1.43-1.55). Moreover, significant interactions were detected between FHS and health-riskbehaviors (tobacco smoking and alcohol drinking). Conclusions FHS is an independent risk factor for stroke in Chinese. The more first degree relativesare affected by stroke, the higher are individuals’ risk of suffering from stroke. The management ofthe health-risk behaviors for reducing stroke should be highlighted, especially for the individualswith FHS.

Genome-Wide Association Study in East Asians Identifies Novel Susceptibility Loci for Breast Cancer

Long, Jirong,Cai, Qiuyin,Sung, Hyuna,Shi, Jiajun,Zhang, Ben,Choi, Ji-Yeob,Wen, Wanqing,Delahanty, Ryan J.,Lu, Wei,Gao, Yu-Tang,Shen, Hongbing,Park, Sue K.,Chen, Kexin,Shen, Chen-Yang,Ren, Zefang,Haima Public Library of Science 2012 PLoS genetics Vol.8 No.2

<P>Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (<I>TAB2</I>) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a <I>P</I>-value of 3.8×10<SUP>−12</SUP> in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (<I>P</I> = 1.9×10<SUP>−6</SUP> from the combined analysis of all samples), located in intron 5 of the <I>ESR1</I> gene, and SNP rs7107217 (<I>P</I> = 4.6×10<SUP>−7</SUP>), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the <I>TAB2</I> gene (6q25.1), and identifies two possible susceptibility loci located in the <I>ESR1</I> gene and 11q24.3, respectively.</P><P><B>Author Summary</B></P> <P>Breast cancer is one of the most common malignancies among women worldwide. Genetic factors play an important role in the etiology of breast cancer. To identify common genetic susceptibility alleles for breast cancer, we performed a four-stage genome-wide association study in 19,091 cases and 20,606 controls among East-Asian women. Single nucleotide polymorphism (SNP) rs9485372, near the TGF-beta activated kinase 1 (<I>TAB2</I>) gene at chromosome 6q25.1, was associated with breast cancer risk (<I>P</I> = 3.8×10<SUP>−12</SUP>). SNPs rs9383951, located in intron 5 of the estrogen receptor 1 (<I>ESR1</I>) gene, and rs7107217, located at 11q24.3, were also consistently associated with breast cancer risk in all four stages with a combined <I>P</I> of 1.9×10<SUP>−6</SUP> and 4.6×10<SUP>−7</SUP>, respectively. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the <I>TAB2</I> gene (6q25.1), and identifies two possible susceptibility loci located in the <I>ESR1</I> gene and 11q24.3, respectively.</P>

Genetic variations in DROSHA and DICER and survival of advanced non-small cell lung cancer: a two-stage study in Chinese population

Shuangshuang Wu,Yun Pan,Songyu Cao,Jiali Xu,Yan Liang,Yan Wang,Lei Chen,Yunyan Wei,Chongqi Sun,Weihong Zhao,Zhibin Hu,Hongxia Ma,Hongbing Shen,Jianqing Wu 한국유전학회 2015 Genes & Genomics Vol.37 No.7

MicroRNAs (miRNA) are a class of small, noncoding RNA molecules involved in carcinogenesis. Genetic variations in miRNA processing genes may affect the biogenesis of miRNAs, and consequently affect miRNAs regulation and development and progression of human cancer. Therefore, we hypothesized that polymorphisms in two main miRNA biosynthesis genes (DROSHA and DICER) may modulate the survival of advanced non-small cell lung cancer (NSCLC) patients in China. We selected 36 common tagging SNPs in DROSHA and DICER and evaluated the associations of these SNPs with survival of advanced NSCLC patients by a two-stage study in Chinese Han population (discovery cohort: 303 patients; replication cohort: 340 patients). Thirty-six SNPs were detected in the discovery cohort and 12 promising SNPs were validated in the replication cohort. The results showed that DROSHA rs3805525 was marginally associated with the survival of NSCLC patients in the replication cohort (dominant model: HR 0.69, 95 % CI 0.46–1.03, P = 0.071), which was in the same direction as that in the discovery cohort. When combing all patients into one group, three SNPs (rs3805525, rs17410035 and rs7719497) in DROSHA showed significantly associations with NSCLC survival (additive model: HR 0.82, 95 % CI 0.68–0.99 for rs3805525; HR 0.79, 95 % CI 0.62–1.00 for rs17410035; HR 0.76, 95 % CI 0.62–0.93 for rs7719497). Additionally, the combined analysis of those three SNPs showed a significant locus-dosage effect between number of favorable alleles and death risk of NSCLC (Trend P = 0.002). Genetic variations in DROSHA might be associated with the survival of advanced NSCLC patients in Chinese population.

Family History of Cancer and Head and Neck Cancer Risk in a Chinese Population

Huang, Yu-Hui Jenny,Lee, Yuan-Chin Amy,Li, Qian,Chen, Chien-Jen,Hsu, Wan-Lun,Lou, Pen-Jen,Zhu, Cairong,Pan, Jian,Shen, Hongbing,Ma, Hongxia,Cai, Lin,He, Baochang,Wang, Yu,Zhou, Xiaoyan,Ji, Qinghai,Zho Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Background: The aim of this study was to investigate whether family history of cancer is associated with head and neck cancer risk in a Chinese population. Materials and Methods: This case-control study included 921 cases and 806 controls. Recruitment was from December 2010 to January 2015 in eight centers in East Asia. Controls were matched to cases with reference to sex, 5-year age group, ethnicity, and residence area at each of the centers. Results: We observed an increased risk of head and neck cancer due to first degree family history of head and neck cancer, but after adjustment for tobacco smoking, alcohol drinking and betel quid chewing the association was no longer apparent. The adjusted OR were 1.10 (95% CI=0.80-1.50) for family history of tobacco-related cancer and 0.96 (95%CI=0.75-1.24) for family history of any cancer with adjustment for tobacco, betel quid and alcohol habits. The ORs for having a first-degree relative with HNC were higher in all tobacco/alcohol subgroups. Conclusions: We did not observe a strong association between family history of head and neck cancer and head and neck cancer risk after taking into account lifestyle factors. Our study suggests that an increased risk due to family history of head and neck cancer may be due to shared risk factors. Further studies may be needed to assess the lifestyle factors of the relatives.