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| 001 | 180090 | ||
| 005 | 20240229145604.0 | ||
| 024 | 7 | _ | |a 10.1093/jnci/djac094 |2 doi |
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| 100 | 1 | _ | |a Tian, Yu |0 P:(DE-He78)834e8bc4d74592e3b999100c157215f5 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Genome-Wide Interaction Analysis of Genetic Variants with Menopausal Hormone Therapy for Colorectal Cancer Risk. |
| 260 | _ | _ | |a Oxford |c 2022 |b Oxford Univ. Press |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a #EA:C020#LA:C020# / 2022 Aug 8;114(8):1135-1148 |
| 520 | _ | _ | |a 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. |
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