BACKGROUND: The link between colorectal cancer (CRC) and type 2 diabetes mellitus (T2D) has been extensively studied. Although it is commonly accepted that T2D is a risk factor for CRC, the underlying mechanisms are still poorly understood. RESEARCH DESIGN AND METHODS: Given that the genetic background contributes to both traits, it is conceivable that genetic variants associated with T2D may also influence the risk of CRC. We selected 26 T2D-related single-nucleotide polymorphisms (SNP) previously identified by genome-wide association studies and assessed their association with CRC and their interaction with known risk factors (gender, T2D, and body mass index) of CRC. Selected SNP were genotyped in 1798 CRC cases and 1810 controls from the population-based Darmkrebs: Chancen der Verhütung durch Screening (DACHS) study (Germany). RESULTS: Patients carrying the TCF7L2_rs7903146_T allele had an increased risk of CRC (P(trend) = 0.02), whereas patients harboring the IL13_rs20541_T allele had a reduced risk (P(trend) = 0.02). A further analysis revealed gender-specific effects: the TCF7L2_rs7903146_T allele was associated with an increased risk of CRC in women (P(trend) = 0.003) but not in men (P(interaction) = 0.06); the LTA_rs1041981_A allele was associated with a decreased risk for CRC in women (P(trend) = 0.02), with an opposite effect in men (P(trend) = 0.05; P(interaction) = 0.002); the CDKAL1_rs7754840_C allele was associated with a decreased risk for CRC in men (P(trend) = 0.03), with no effect in women (P(interaction) = 0.03). The risk associated with the presence of T2D was modified both by IGF2BP2_rs4402960 and PPARγ_rs1801282 SNP (P(interaction) = 0.04 and 0.04, respectively). None of the findings were significant after correction for multiple comparisons. CONCLUSIONS: These findings suggest that T2D-related variants modify CRC risk independently and/or in an interactive manner according to the gender and the presence or absence of T2D.
BACKGROUND: The link between colorectal cancer (CRC) and type 2 diabetes mellitus (T2D) has been extensively studied. Although it is commonly accepted that T2D is a risk factor for CRC, the underlying mechanisms are still poorly understood. RESEARCH DESIGN AND METHODS: Given that the genetic background contributes to both traits, it is conceivable that genetic variants associated with T2D may also influence the risk of CRC. We selected 26 T2D-related single-nucleotide polymorphisms (SNP) previously identified by genome-wide association studies and assessed their association with CRC and their interaction with known risk factors (gender, T2D, and body mass index) of CRC. Selected SNP were genotyped in 1798 CRC cases and 1810 controls from the population-based Darmkrebs: Chancen der Verhütung durch Screening (DACHS) study (Germany). RESULTS:Patients carrying the TCF7L2_rs7903146_T allele had an increased risk of CRC (P(trend) = 0.02), whereas patients harboring the IL13_rs20541_T allele had a reduced risk (P(trend) = 0.02). A further analysis revealed gender-specific effects: the TCF7L2_rs7903146_T allele was associated with an increased risk of CRC in women (P(trend) = 0.003) but not in men (P(interaction) = 0.06); the LTA_rs1041981_A allele was associated with a decreased risk for CRC in women (P(trend) = 0.02), with an opposite effect in men (P(trend) = 0.05; P(interaction) = 0.002); the CDKAL1_rs7754840_C allele was associated with a decreased risk for CRC in men (P(trend) = 0.03), with no effect in women (P(interaction) = 0.03). The risk associated with the presence of T2D was modified both by IGF2BP2_rs4402960 and PPARγ_rs1801282 SNP (P(interaction) = 0.04 and 0.04, respectively). None of the findings were significant after correction for multiple comparisons. CONCLUSIONS: These findings suggest that T2D-related variants modify CRC risk independently and/or in an interactive manner according to the gender and the presence or absence of T2D.
Authors: Zhiguo Zhao; Wanqing Wen; Kyriaki Michailidou; Manjeet K Bolla; Qin Wang; Ben Zhang; Jirong Long; Xiao-Ou Shu; Marjanka K Schmidt; Roger L Milne; Montserrat García-Closas; Jenny Chang-Claude; Sara Lindstrom; Stig E Bojesen; Habibul Ahsan; Kristiina Aittomäki; Irene L Andrulis; Hoda Anton-Culver; Volker Arndt; Matthias W Beckmann; Alicia Beeghly-Fadiel; Javier Benitez; Carl Blomqvist; Natalia V Bogdanova; Anne-Lise Børresen-Dale; Judith Brand; Hiltrud Brauch; Hermann Brenner; Barbara Burwinkel; Qiuyin Cai; Graham Casey; Georgia Chenevix-Trench; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Thilo Dörk; Martine Dumont; Peter A Fasching; Jonine Figueroa; Dieter Flesch-Janys; Olivia Fletcher; Henrik Flyger; Florentia Fostira; Marilie Gammon; Graham G Giles; Pascal Guénel; Christopher A Haiman; Ute Hamann; Patricia Harrington; Mikael Hartman; Maartje J Hooning; John L Hopper; Anna Jakubowska; Farzana Jasmine; Esther M John; Nichola Johnson; Maria Kabisch; Sofia Khan; Muhammad Kibriya; Julia A Knight; Veli-Matti Kosma; Mieke Kriege; Vessela Kristensen; Loic Le Marchand; Eunjung Lee; Jingmei Li; Annika Lindblom; Artitaya Lophatananon; Robert Luben; Jan Lubinski; Kathleen E Malone; Arto Mannermaa; Siranoush Manoukian; Sara Margolin; Frederik Marme; Catriona McLean; Hanne Meijers-Heijboer; Alfons Meindl; Hui Miao; Kenneth Muir; Susan L Neuhausen; Heli Nevanlinna; Patrick Neven; Janet E Olson; Barbara Perkins; Paolo Peterlongo; Kelly-Anne Phillips; Katri Pylkäs; Anja Rudolph; Regina Santella; Elinor J Sawyer; Rita K Schmutzler; Minouk Schoemaker; Mitul Shah; Martha Shrubsole; Melissa C Southey; Anthony J Swerdlow; Amanda E Toland; Ian Tomlinson; Diana Torres; Thérèse Truong; Giske Ursin; Rob B Van Der Luijt; Senno Verhoef; Shan Wang-Gohrke; Alice S Whittemore; Robert Winqvist; M Pilar Zamora; Hui Zhao; Alison M Dunning; Jacques Simard; Per Hall; Peter Kraft; Paul Pharoah; David Hunter; Douglas F Easton; Wei Zheng Journal: Cancer Causes Control Date: 2016-04-06 Impact factor: 2.506
Authors: José Manuel Sánchez-Maldonado; Ricardo Collado; Antonio José Cabrera-Serrano; Rob Ter Horst; Fernando Gálvez-Montosa; Inmaculada Robles-Fernández; Verónica Arenas-Rodríguez; Blanca Cano-Gutiérrez; Olivier Bakker; María Inmaculada Bravo-Fernández; Francisco José García-Verdejo; José Antonio López López; Jesús Olivares-Ruiz; Miguel Ángel López-Nevot; Laura Fernández-Puerta; José Manuel Cózar-Olmo; Yang Li; Mihai G Netea; Manuel Jurado; Jose Antonio Lorente; Pedro Sánchez-Rovira; María Jesús Álvarez-Cubero; Juan Sainz Journal: Cancers (Basel) Date: 2022-05-12 Impact factor: 6.575