Genetics of gallbladder cancer Authors’ reply
We would like to thank Kari Hemminki and colleagues for presenting empirical familial relative risk (FRR) estimates for gallbladder cancer based on the Swedish Family-Cancer Data (SFCD) providing a benchmark for comparison of heritability estimation for this rare malignancy. We do not find it surprising that the point estimate of GWAS FRR (FRR 3·15 [95% CI 1·80–5·49])1 from our study of Indian origin was higher than that from the empirical estimate in SFCD (2·47 [1·59–3·65]) in view of the difference in underlying populations and the large confidence intervals in both sets of estimates. Both these estimates qualitatively suggest that gallbladder cancer might have a stronger heritable component than most other cancers, which tend to have FRR between 1·5 and 2·5.2 The observation that in SFCD, FRR associated with mothers’ disease history was markedly higher than that associated with fathers is intriguing. We do not provide sex-specific heritability estimates here because of limited power, but appendix table 6 in our paper indicates that risk in SNPs reaching genome-wide significance was potentially higher for females.2 In the future, we plan to present more detailed analysis of empirical FRR and GWAS heritability stratified by sex as we accrue enough participants in our study to allow sufficient power for such analysis.
Mhatre S, Wang Z, Nagrani R, et al. Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study. Lancet Oncol 2017; 18: 535–44. Sampson JN, Wheeler WA, Yeager M, et al. Analysis of heritability and shared heritability based on genome-wide association studies for thirteen cancer types. J Natl Cancer Inst 2015; 107: djv279.
We declare no competing interests.
Sharayu Mhatre, Nilanjan Chatterjee†,* Rajesh Dikshit†, Preetha Rajaraman† [email protected]
These authors jointly directed this work.
Centre for Cancer Epidemiology, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India (SM, RD); Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA (NC); and Centre for Global Health, National Cancer Institute, NIH, Rockville, MD, USA (PR)
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