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young to have cancer’: A blueprint for research using family and twin studies  \nJohn L. Hopper1 | Shuai Li1,2,3,4  | Robert J. MacInnis1,5 | James G. Dowty1 | Tuong L. Nguyen1  | Minh Bui1 | Gillian S. Dite1,6 | Vivienne F. C. Esser1 | Zhoufeng Ye1  | Enes Makalic1 | Daniel F. Schmidt7 |  \nBenjamin Goudey8,9  | Karen Alpen1 | Miroslaw Kapuscinski1 | Aung Ko Win1,10,11 | Pierre‐Antoine Dugué1,4,5 | Roger L. Milne1,4,5 | Harindra Jayasekara1,5 | Jennifer D. Brooks12  | Sue Malta1 |  \nLucas Calais‐Ferreira1  | Alexander C. Campbell1,3 | Jesse T. Young1,12,13,14,15,16 |  \nTu Nguyen‐Dumont4 | Joohon Sung17,18,19 | Graham G. Giles1,4,5 | Daniel Buchanan20 | Ingrid Winship21 | Mary Beth Terry22 | Melissa C. Southey4,5,20 | Mark A. Jenkins1,10  \nCorrespondence  \nJohn L. Hopper, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, 207 Bouverie St, Carlton, VIC 3053, Australia.  \nEmail: [j.hopper@unimelb.edu.au](j.hopper@unimelb.edu.au)  \nFunding information  \nNational Health and Medical Research Council, Grant/Award Numbers:  \nGNT2017373, GNT1178027; Suicide Prevention Australia; National Research  \nFoundation of Korea (NRF), Grant/Award Numbers:  \n2020R1A2C2101041, 2023R1A2C2002925  \nAbstract  \nYoung breast and bowel cancers (e.g., those diagnosed before age 40 or 50 years) have far greater morbidity and mortality in terms of years of life lost, and are increasing in incidence, but have been less studied. For breast and bowel cancers, the familial relative risks, and therefore the familial variancesin age‐specific log(incidence), are much greater at younger ages, but little of these familial variances has been explained. Studies of families and twins can address questions not easily answered by studies of unrelated individuals alone. We describe existing and emerging family and twin data that can provide special opportunities for discovery. We present designs and statistical analyses, including novel ideas such as the VALID (Variance in Age‐specific Log Incidence Decomposition) model for causes of variation in risk, the DEPTH (DEPendency of association on the number of Top Hits) and other approaches to analyse genome‐wide association study data, and the within‐ pair, ICE FALCON (Inference about Causation from Examining FAmiliaL CONfounding) and ICE CRISTAL (Inference about Causation from  \nFor affiliations refer to page 442 .  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2024 The Authors. Genetic Epidemiology published by Wiley Periodicals LLC.  \nExamining Changes in Regression coefficients and Innovative STatistical AnaLysis) approaches to causation and familial confounding. Example applications to breast and colorectal cancer are presented. Motivated by the availability of the resources of the Breast and Colon Cancer Family Registries, we also present some ideas for future studies that could be applied to, and compared with, cancers diagnosed at older ages and address the challenges posed by young breast and bowel cancers.  \nKEYW OR DS  \nbreast cancer, causation, colorectal cancer, DEPTH, familial confounding, family data, ICE CRISTAL, ICE FALCON, statistical methods, twin studies, VALID  \n1 | INTRODUCTION  \n1.1 | The problem: Breast and bowel cancers diagnosed in persons ‘too young to have cancer’  \nBreast and bowel (colorectal) cancers are two of the most common cancers worldwide, with average ages at diagnosis in the 60s. An important minority of these cancers are diagnosed at young ages (e.g., breast cancers diagnosed before age 40 or bowel cancers before age 50) before population screening typically commences, after clinical presentation and typically at a later stage. These young cancers have far greater ph","cbCailPkwkaFlZfK","https://ap.wps.com/l/cbCailPkwkaFlZfK","pdf",1283301,15,"English","# Abstract\n# Introduction\n## The problem: Breast and bowel cancers diagnosed in persons ‘too young to have cancer’\n## Knowledge gaps","[{\"question\":\"Why are young breast and bowel cancers particularly important to study?\",\"answer\":\"They have greater morbidity and mortality, larger years of life lost, and increasing incidence, yet they are diagnosed before screening typically begins and have major physical, socioeconomic, and psychological impact.\"},{\"question\":\"What makes familial relative risks useful for research in younger-onset cancers?\",\"answer\":\"Familial relative risks and familial variances in age-specific risk are much larger at younger ages, creating stronger opportunities to discover causes.\"},{\"question\":\"How do family and twin studies support research beyond unrelated-individual studies?\",\"answer\":\"They address questions that cannot be answered by studying unrelated individuals alone, and they enable designs and statistical analyses tailored to familial and twin data, including models for analyzing variation and causation.\"}]","Breast and bowel cancers diagnosed in people ‘too young to have cancer’: A blueprint for research using family and twin studies | PDF",1789999496,38]