Estimation of heritability for nine common cancers using data from genome-wide association studies in Chinese population.
The familial aggregation indicated the inheritance of cancer risk. Recent genome-wide association studies (GWASs) have identified a number of common single-nucleotide polymorphisms (SNPs). Following heritability analyses have shown that SNPs could explain a moderate amount of variance for different cancer phenotypes among Caucasians. However, little information was available in Chinese population. We performed a genome-wide complex trait analysis for common cancers at nine anatomical sites in Chinese population (14,629 cancer cases vs. 17,554 controls) and estimated the heritability of these cancers based on the common SNPs. We found that common SNPs explained certain amount of heritability with significance for all nine cancer sites: gastric cancer (20.26%), esophageal squamous cell carcinoma (19.86%), colorectal cancer (16.30%), lung cancer (LC) (15.17%), and epithelial ovarian cancer (13.31%), and a similar heritability around 10% for hepatitis B virus-related hepatocellular carcinoma, prostate cancer, breast cancer and nasopharyngeal carcinoma. We found that nearly or less than 25% change was shown when removing the regions expanding 250 kb or 500 kb upward and downward of the GWAS-reported SNPs. We also found strong linear correlations between variance partitioned by each chromosome and chromosomal length only for LC (R2= 0.641, p = 0.001) and esophageal squamous cell cancer (R2= 0.633, p = 0.002), which implied us the complex heterogeneity of cancers. These results indicate polygenic genetic architecture of the nine common cancers in Chinese population. Further efforts should be made to discover the hidden heritability of different cancer types among Chinese.
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Juncheng
J
Dai
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Wei
W
Shen
Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University of Medical Center, Nashville, TN.
Wanqing
W
Wen
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.|Institute of Occupational Medicine and Ministry of Education Key Lab for Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Jiang
J
Chang
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
Tongmin
T
Wang
Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
Haitao
H
Chen
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Guangfu
G
Jin
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Hongxia
H
Ma
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Chen
C
Wu
Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
Lian
L
Li
Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
Fengju
F
Song
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
YiXin
Y
Zeng
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Yue
Y
Jiang
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Jiaping
J
Chen
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Cheng
C
Wang
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Meng
M
Zhu
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Wen
W
Zhou
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Jiangbo
J
Du
Shanghai Cancer Institute, Shanghai, People's Republic of China.
Yongbing
Y
Xiang
Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University of Medical Center, Nashville, TN.
Xiao-Ou
XO
Shu
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Zhibin
Z
Hu
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Weiping
W
Zhou
Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
Kexin
K
Chen
Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
Jianfeng
J
Xu
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
Weihua
W
Jia
State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Dongxin
D
Lin
Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University of Medical Center, Nashville, TN.
Wei
W
Zheng
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Hongbing
H
Shen
D044466:Asian People / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
Chinese population; cancer; genome-wide complex trait analysis; heritability; single-nucleotide polymorphisms
Gynecol Oncol. 2010 Oct;119(1):7-17
20692025
N Engl J Med. 2000 Jul 13;343(2):78-85
10891514
Nat Genet. 2011 Jun;43(6):519-25
21552263
Hum Mol Genet. 2013 Feb 15;22(4):832-41
23193196
Am J Hum Genet. 2009 Aug;85(2):194-203
19664746
Sci Rep. 2015 Jul 24;5:12473
26208354
Nat Genet. 2010 Jul;42(7):599-603
20512145
Annu Rev Genet. 2013;47:75-95
23988118
Am J Hum Genet. 2011 Mar 11;88(3):294-305
21376301
PLoS Genet. 2012;8(7):e1002791
22807686
Nat Genet. 2011 Jul 03;43(8):792-6
21725308
Carcinogenesis. 2015 Sep;36(9):992-8
26045304
Gynecol Oncol. 2013 Jul;130(1):107-14
23558050
JAMA. 2016 Jan 5;315(1):68-76
26746459
Int J Cancer. 2004 Nov 10;112(3):451-7
15382071
Nat Genet. 2011 Oct 30;43(12):1215-8
22037551
Nature. 2013 Sep 19;501(7467):338-45
24048066
Hum Genet. 2012 Oct;131(10):1655-64
22821350
Nat Genet. 2014 Aug;46(8):886-90
25038754
Int J Cancer. 2002 May 10;99(2):260-6
11979442
Hum Mol Genet. 2014 Nov 15;23(22):6112-8
24943595
Gut. 2015 Oct;64(10):1623-36
26187503
Nat Genet. 2015 Apr;47(4):373-80
25751625
Chin J Cancer. 2012 Sep;31(9):421-9
22085526
Nat Genet. 2014 Oct;46(10):1103-9
25217961
Nat Commun. 2014 Aug 19;5:4682
25134534
Nat Genet. 2012 Nov;44(11):1231-5
23023329
Br J Cancer. 2004 May 4;90(9):1765-70
15208620
Clin Otolaryngol Allied Sci. 2001 Apr;26(2):82-92
11309046
J Hum Genet. 2009 Jul;54(7):392-7
19478819
Am J Hum Genet. 2011 Jan 7;88(1):76-82
21167468
JAMA. 2007 Dec 26;298(24):2869-76
18159056
Nat Genet. 2016 Jan;48(1):30-5
26569126
Nat Genet. 2011 Jun 05;43(7):679-84
21642993
Nat Genet. 2014 Jun;46(6):533-42
24836286
Nat Rev Genet. 2005 Feb;6(2):95-108
15716906
Nat Genet. 2009 Sep;41(9):996-1000
19648919
Int J Cancer. 2001 Apr 1;92(1):144-50
11279618
Nature. 2008 Nov 6;456(7218):18-21
18987709
CA Cancer J Clin. 2015 Mar;65(2):87-108
25651787
Carcinogenesis. 2013 Mar;34(3):487-502
23349013
Nature. 2009 Oct 8;461(7265):747-53
19812666
J Natl Cancer Inst. 2015 Oct 12;107(12):djv279
26464424
Hum Mol Genet. 2014 Jul 15;23(14):3898-905
24562164
Hum Mol Genet. 2012 Nov 15;21(22):4996-5009
22892372
Nat Genet. 2010 Jul;42(7):565-9
20562875