1. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer:Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses
- Author
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Khankari, Nikhil K., Shu, Xiao Ou, Wen, Wanqing, Kraft, Peter, Lindström, Sara, Peters, Ulrike, Schildkraut, Joellen, Schumacher, Fredrick, Bofetta, Paolo, Risch, Angela, Bickeböller, Heike, Amos, Christopher I., Easton, Douglas, Eeles, Rosalind A., Gruber, Stephen B., Haiman, Christopher A., Hunter, David J., Chanock, Stephen J., Pierce, Brandon L., Zheng, Wei, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, dos Santos Silva, Isabel, Ahsan, Habib, Whittemore, Alice, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel, van der Luijt, Rob B., Uitterlinden, Andre G., Hofman, Albert, Meindl, Alfons, Schmutzler, Rita K., Müller-Myhsok, Bertram, Lichtner, Peter, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Hein, Rebecca, Dahmen, Norbert, Beckman, Lars, Crisponi, Laura, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Easton, Douglas F., Turnbull, Clare, Rahman, Nazneen, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Giles, Graham, Neal, David, Donovan, Jenny L., Hamdy, Freddie C., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher, Schumacher, Fred, Travis, Ruth, Riboli, Elio, Hunter, David, Gapstur, Susan, Berndt, Sonja, Chanock, Stephen, Han, Younghun, Su, Li, Wei, Yongyue, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, McKay, James D., Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil, Teresa Landi, Maria, Heinrich, Joachim, Wu, Xifeng, Ye, Yuanqing, Christiani, David C., Human genetics, CCA - Evaluation of Cancer Care, Eeles, Rosalind A [0000-0002-7472-5384], and Apollo - University of Cambridge Repository
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Oncology ,Male ,Lung Neoplasms ,Social Sciences ,Genome-wide association study ,Biochemistry ,0302 clinical medicine ,Sociology ,Odds Ratio ,Prospective Studies ,Aged, 80 and over ,Prostate Diseases ,11 Medical And Health Sciences ,General Medicine ,Genomics ,3. Good health ,030220 oncology & carcinogenesis ,Meta-analysis ,Physical Sciences ,Transdisciplinary Research in Cancer of the Lung (TRICL) ,Medicine ,DIFFERENT ANATOMIC SITES ,BODY-MASS-INDEX ,Statistics (Mathematics) ,medicine.medical_specialty ,03 medical and health sciences ,Exocrine Glands ,SDG 3 - Good Health and Well-being ,Genome-Wide Association Studies ,Genetics ,Humans ,Statistical Methods ,Molecular Biology ,RECTAL-CANCER ,Aged ,Science & Technology ,Biology and Life Sciences ,Computational Biology ,Genetic Variation ,Odds ratio ,Mendelian Randomization Analysis ,medicine.disease ,Genitourinary Tract Tumors ,030104 developmental biology ,Relative risk ,OLDER WOMEN ,Prostate Gland ,Mathematics ,Meta-Analysis ,Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) ,0301 basic medicine ,Bioinformatics ,Lung and Intrathoracic Tumors ,Mathematical and Statistical Techniques ,NETHERLANDS COHORT ,Consortia ,Risk Factors ,GROWTH-FACTOR (IGF)-I ,Medicine and Health Sciences ,Prospective cohort study ,Prostate Cancer ,Middle Aged ,Research Design ,Female ,Anatomy ,Colorectal Neoplasms ,Life Sciences & Biomedicine ,NORWEGIAN MEN ,Research Article ,Biotechnology ,Adult ,Urology ,IGF-BINDING PROTEINS ,Research and Analysis Methods ,Young Adult ,Medicine, General & Internal ,Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) ,General & Internal Medicine ,Internal medicine ,Mendelian randomization ,medicine ,Journal Article ,Colorectal Transdisciplinary Study (CORECT) ,Lung cancer ,Colorectal Cancer ,business.industry ,Cancers and Neoplasms ,Prostatic Neoplasms ,JAPANESE MEN ,Human Genetics ,Cell Biology ,Genome Analysis ,Body Height ,Prostate cancer ,Lung and intrathoracic tumors ,Prospective studies ,Colorectal cancer ,Prostate gland ,Genome-wide association studies ,FOLLOW-UP ,business ,Genome-Wide Association Study - Abstract
Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers., In a Mendelian randomisation study Pierce and colleagues show a genetic association between adult height and increased risk of colorectal and lung cancer., Author Summary Why Was This Study Done? Several previous observational studies have examined the association between adult height and risk of cancers of the lung, colon/rectum, and prostate; however, it remains unclear whether adult height is indeed related to the risk of these cancers. What Did the Researchers Do and Find? We conducted a systematic review and meta-analysis of prospective cohort studies that examined the association between adult height and the risk of colorectal, lung, and prostate cancers. To overcome inherent limitations of observational study designs, we conducted Mendelian randomization analyses using genetic data generated from a large multi-center consortium study including 47,800 cases and 81,353 controls. In the meta-analysis of the prospective observational studies, we found a 12% increased risk of colorectal cancer, a 7% increased risk of prostate cancer, and a 6% increased risk of lung cancer for every ten-centimeter increase in height, and this increased risk was corroborated in the Mendelian randomization analyses for colorectal (58%) and lung cancer (10%). What Do These Findings Mean? Our study provides strong evidence for an association between adult height and risk of colorectal and lung cancer, and suggests that certain genetic and biological factors that affect height may also affect the risk of these cancers. However, our meta-analysis was limited to published studies, and the sample size for the Mendelian randomization analysis for colorectal cancer was relatively small, affecting the precision of the risk estimate.
- Published
- 2016