Journal Article

DKFZ-2022-01089

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genome-Wide Interaction Analysis of Genetic Variants with Menopausal Hormone Therapy for Colorectal Cancer Risk.

Tian, Y. (First author)DKFZ* ; Kim, A. E. ; Bien, S. A. ; Lin, Y. ; Qu, C. ; Harrison, T. ; Carreras-Torres, R. ; Díez-Obrero, V. ; Dimou, N. ; Drew, D. A. ; Hidaka, A. ; Huyghe, J. R. ; Jordahl, K. M. ; Morrison, J. ; Murphy, N. ; Obón-Santacana, M. ; Ulrich, C. M. ; Ose, J. ; Peoples, A. R. ; Ruiz-Narvaez, E. A. ; Shcherbina, A. ; Stern, M. ; Su, Y.-R. ; van Duijnhoven, F. J. B. ; Arndt, V.DKFZ* ; Baurley, J. ; Berndt, S. I. ; Bishop, D. T. ; Brenner, H.DKFZ* ; Buchanan, D. D. ; Chan, A. T. ; Figueiredo, J. C. ; Gallinger, S. ; Gruber, S. B. ; Harlid, S. ; Hoffmeister, M.DKFZ* ; Jenkins, M. A. ; Joshi, A. D. ; Keku, T. O. ; Larsson, S. C. ; Le Marchand, L. ; Li, L. ; Giles, G. G. ; Milne, R. L. ; Nan, H. ; Nassir, R. ; Ogino, S. ; Budiarto, A. ; Platz, E. A. ; Potter, J. D. ; Prentice, R. L. ; Rennert, G. ; Sakoda, L. C. ; Schoen, R. E. ; Slattery, M. L. ; Thibodeau, S. N. ; Van Guelpen, B. ; Visvanathan, K. ; White, E. ; Wolk, A. ; Woods, M. O. ; Wu, A. H. ; Campbell, P. T. ; Casey, G. ; Conti, D. V. ; Gunter, M. J. ; Kundaje, A. ; Lewinger, J. P. ; Moreno, V. ; Newcomb, P. A. ; Pardamean, B. ; Thomas, D. C. ; Tsilidis, K. K. ; Peters, U. ; Gauderman, W. J. ; Hsu, L. ; Chang-Claude, J. (Last author)DKFZ*

2022
Oxford Univ. Press Oxford

This record in other databases:  

Please use a persistent id in citations: doi:10.1093/jnci/djac094

Abstract: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.We conducted a genome-wide gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen-only, and combined estrogen-progestogen therapy with CRC risk, among 28,486 postmenopausal women (11,519 cases and 16,967 controls) from 38 studies, using logistic regression, two-step method, and 2- or 3-degree-of-freedom (d.f.) joint test. A set-based score test was applied for rare genetic variants.The use of any MHT, estrogen-only and estrogen-progestogen were associated with a reduced CRC risk [odds ratio (OR) with 95% confidence interval (95% CI) of 0.71 (0.64-0.78), 0.65 (0.53-0.79), and 0.73 (0.59-0.90), respectively]. The two-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was significantly reduced in women with the GG genotype [0.68 (0.64-0.72)] but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-d.f. joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing ORs of 0.78 (0.70-0.87) for TT, 0.68 (0.63-0.73) for TC, and 0.66 (0.60-0.74) for CC genotypes. In addition, five genes in rare variant analysis showed suggestive interactions with MHT (two-sided P < 1.2x10-4).Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

Note: #EA:C020#LA:C020# / 2022 Aug 8;114(8):1135-1148

---

Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C071 Cancer Survivorship (C071)
3. C070 Klinische Epidemiologie und Alternf. (C070)
4. Präventive Onkologie (C120)
5. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---