title: Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese.
abstract: Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10(-8) to 8.96 × 10(-6) for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10-1.19 and OR = 1.17, 95% CI, 1.12-1.21), with the p values being 1.20 × 10(-12) and 1.26 × 10(-16), respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers.
authors.affiliation: Department of Epidemiology and Biostatistics and Ministry of Education Key Laboratory for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.forename: Ruyang
authors.initials: R
authors.lastname: Zhang
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.forename: Huizhang
authors.initials: H
authors.lastname: Li
authors.forename: Shandong
authors.initials: S
authors.lastname: Pan
authors.forename: Minjie
authors.initials: M
authors.lastname: Chu
authors.forename: Feng
authors.initials: F
authors.lastname: Lu
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Lingmin
authors.initials: L
authors.lastname: Hu
authors.forename: Yijiang
authors.initials: Y
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.forename: Shiyang
authors.initials: S
authors.lastname: Pan
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Baosen
authors.initials: B
authors.lastname: Zhou
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D002681:China / Q000453:epidemiology; D002896:Chromosomes, Human, Pair 6; D002897:Chromosomes, Human, Pair 7; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics