PMID: 21490239

Rudolph A, Sainz J, Hein R, Hoffmeister M, Frank B, Forsti A, Brenner H, Hemminki K, Chang-Claude J
Modification of menopausal hormone therapy-associated colorectal cancer risk by polymorphisms in sex steroid signaling, metabolism and transport related genes.
Endocr Relat Cancer. 2011 Jun 8;18(3):371-84. Print 2011., [PubMed]
Sentences
No. Mutations Sentence Comment
119 ABCB1 p.Ser400Asn
X
ABCB1 p.Ser400Asn 21490239:119:546
status: NEW
view ABCB1 p.Ser400Asn details
ABCB1 p.Asn21Asp
X
ABCB1 p.Asn21Asp 21490239:119:865
status: NEW
view ABCB1 p.Asn21Asp details
 Table 2 Genotype frequencies and colorectal cancer risk estimates of polymorphisms in genes related to sex steroid signaling, transport, and metabolism in the female postmenopausal DACHS study population Gene Variant Genotype Effect estimate dbSNP rs# Amino acid substitution and functional consequence MAF Genotype N Co/N Ca OR (95% CI)a P trend ABCB1 rs1045642 I1145I, T allele associated with lower protein expression (Hoffmeyer et al. 2000) 49% T/T 183/190 1.00 T/C 329/336 1.04 (0.77-1.40) C/C 167/156 0.98 (0.69-1.39) 0.914 ABCB1 rs2229109 S400N, functional consequences unknown 6% G/G 596/614 1.00 G/A 86/64 0.69 (0.47-1.03) A/A 1/1 1.00 (0.03-33.9) 0.078 ABCB1 rs1202168 Intronic, functional consequences unknown, in high LD interval (Soranzo et al. 2004) 40% C/C 249/218 1.00 C/T 312/337 1.08 (0.82-1.42) T/T 119/127 1.02 (0.71-1.46) 0.829 ABCB1 rs9282564 N21D, results in a net charge change of the protein (Brinkmann and Eichelbaum 2001) 10% A/A 545/544 1.00 A/G 117/124 1.05 (0.76-1.45) G/G 12/9 0.73 (0.23-2.27) 0.997 ABCB1 rs2214102 50 -UTR, located at a translation initiation site (Hoffmeyer et al. 2000) 7% G/G 593/580 1.00 G/A 81/97 1.33 (0.91-1.92) A/A 6/6 0.96 (0.26-3.51) 0.208 SHBG rs6259 D356N, A allele is associated with reduced clearance of SHBG (Cousin et al. 1998) 11% G/G 525/549 1.00 G/A 141/115 0.69 (0.50-0.95) A/A 6/10 1.13 (0.36-3.60) 0.061 ESR2 rs1255998 30 -UTR, functional consequences unknown, G allele associated with endometrial cancer risk (Ashton et al. 2009) 12% C/C 519/547 1.00 C/G 138/114 0.76 (0.55-1.04) G/G 14/5 0.33 (0.11-1.01) 0.015 ESR2 rs928554 30 -UTR, G allele might create new acceptor splice site (MARIE-GENICA-Consortium 2010a) 40% A/A 246/222 1.00 A/G 316/317 1.19 (0.90-1.56) G/G 111/133 1.48 (1.03-2.13) 0.032 ESR2 rs4986938 30 -UTR, potentially affects pre-mRNA splicing (Zheng et al. 2003) 38% G/G 260/264 1.00 G/A 310/306 0.97 (0.74-1.27) A/A 99/106 1.02 (0.70-1.48) 0.997 ESR2 rs1271572 50 -UTR, might modulate binding of transcription factors (MARIE-GENICA-Consortium 2010a) 42% G/G 231/208 1.00 G/T 329/330 1.29 (0.97-1.70) T/T 120/138 1.40 (0.98-2.00) 0.046 ESR1 rs851984 50 -UTR, functional consequences unknown, T allele associated with breast cancer risk (MARIE-GENICA-Consortium 2010a) 41% C/C 221/231 1.00 C/T 341/314 0.95 (0.72-1.25) T/T 103/122 1.07 (0.74-1.55) 0.833 ESR1 rs2881766 50 -UTR, functional consequences unknown, G allele associated with breast cancer risk (MARIE-GENICA-Consortium 2010a) 18% T/T 461/453 1.00 T/G 190/195 1.02 (0.77-1.35) G/G 25/22 0.95 (0.48-1.87) 0.989 ESR1 rs2071454 50 -UTR, functional consequences unknown 11% T/T 536/551 1.00 T/G 132/120 0.81 (0.59-1.12) G/G 5/8 1.75 (0.51-6.03) 0.467 ESR1 rs2077647 S10S, potentially affects mRNA structure (Tanaka et al. 2003) 47% A/A 183/187 1.00 A/G 347/349 0.97 (0.73-1.30) G/G 140/135 0.93 (0.65-1.33) 0.697 ESR1 rs827421 Intronic, functional consequences unknown 48% T/T 172/178 1.00 T/C 350/355 1.02 (0.76-1.37) C/C 151/143 0.91 (0.64-1.30) 0.620 ESR1 rs2234693 Intronic, C allele introduces a binding site for transcription factor B-myb, leading to altered transcription (Herrington et al. 2002) 46% T/T 188/209 1.00 T/C 348/341 0.93 (0.70-1.24) C/C 136/120 0.87 (0.61-1.24) 0.429 ESR1 rs9340799 Intronic, functional consequences unknown, may lead to altered transcription or splicing (Schuit et al. 2004) 36% A/A 274/287 1.00 A/G 319/317 1.01 (0.78-1.32) G/G 83/72 0.94 (0.63-1.42) 0.864 ESR1 rs3798577 30 -UTR, functional consequences unknown 45% T/T 203/189 1.00 T/C 328/330 1.14 (0.86-1.52) C/C 139/154 1.27 (0.89-1.80) 0.181 Table 2 continued Gene Variant Genotype Effect estimate dbSNP rs# Amino acid substitution and functional consequence MAF Genotype N Co/N Ca OR (95% CI)a P trend ESR1 rs910416 30 near gene, functional consequences unknown, modified estrogen monotherapy- associated breast cancer risk (MARIE-GENICA-Consortium 2010a) 48% T/T 178/188 1.00 T/C 338/314 0.81 (0.61-1.10) C/C 148/159 0.92 (0.65-1.31) 0.599 PGR rs1042838 V660L, SNP possibly affects receptor dimerization, nuclear localization, ligand binding, cofactor interaction (Agoulnik et al. 2004) 15% C/C 495/478 1.00 C/A 154/181 1.32 (0.99-1.76) A/A 24/16 0.91 (0.44-1.88) 0.202 PGR rs1379130 G393G, functional consequences unknown 36% G/G 272/298 1.00 G/A 311/268 0.74 (0.56-0.96) A/A 88/108 1.01 (0.69-1.47) 0.412 PGR rs10895068 50 -UTR, creates new transcription start site, increasing expression of PR-B isoform (De Vivo et al. 2002) 4% G/G 615/619 1.00 G/A 58/59 0.89 (0.58-1.38) A/A 1/1 1.94 (0.05-80.6) 0.670 PGR rs518162 50 -UTR, SNP is located between PR-B and PR-A transcription start sites, potentially affecting PR-A/B expression (De Vivo et al. 2002) 7% G/G 580/586 1.00 G/A 93/88 1.06 (0.74-1.53) A/A 3/4 1.23 (0.21-7.06) 0.710 NR1I2 rs1523127 50 -UTR, belongs to a haplotype incl. SNPs that introduce new transcription factor binding sites (Zhang et al. 2001) 39% A/A 245/258 1.00 A/C 326/317 0.89 (0.68-1.17) C/C 98/88 0.89 (0.61-1.32) 0.450 NR1I2 rs2276706 Intronic, belongs to a haplotype incl. SNPs that introduce new transcription factor binding sites (Zhang et al. 2001) 38% G/G 251/267 1.00 G/A 329/324 0.92 (0.70-1.20) A/A 95/83 0.89 (0.60-1.31) 0.474 NR1I2 rs1464603 Intronic, functional consequences unknown 32% T/T 303/307 1.00 T/C 310/291 1.05 (0.80-1.36) C/C 65/78 1.11 (0.73-1.69) 0.608 NR1I2 rs6785049 Intronic, G allele associated with increased induction of CYP3A (Zhang et al. 2001) 38% A/A 260/264 1.00 A/G 323/313 1.00 (0.77-1.31) G/G 94/101 1.10 (0.75-1.60) 0.698 NR1I2 rs2276707 Intronic, T allele associated with increased induction of CYP3A (Zhang et al. 2001) 17% C/C 446/439 1.00 C/T 180/190 1.00 (0.75-1.32) T/T 21/24 1.19 (0.58-2.44) 0.794 NR1I2 rs1054191 30 -UTR, A allele associated with decreased induction of CYP3A (Zhang et al. 2001) 14% G/G 499/518 1.00 G/A 161/143 0.95 (0.70-1.28) A/A 17/12 0.80 (0.35-1.87) 0.581 NR1I2 rs3814057 30 -UTR, C allele associated with decreased induction of P-glycoprotein (Zhang et al. 2001) 17% A/A 458/440 1.00 A/C 177/201 1.15 (0.87-1.52) C/C 22/24 1.20 (0.60-2.41) 0.307 COMT rs4680 V158M, A allele leads to thermo-labile protein and 2-3 fold lower catalytic activity (Dawling et al. 2001) 49% G/G 171/177 1.00 A/G 343/327 0.88 (0.66-1.19) A/A 162/175 1.05 (0.74-1.48) 0.802 HSD17B1 rs605059 G313S, functional consequences unknown, C allele has been associated with lower estradiol levels (Setiawan et al. 2004) 46% T/T 199/167 1.00 T/C 330/340 1.30 (0.97-1.75) C/C 144/170 1.41 (0.99-2.01) 0.051 CYP1B1 rs1800440 N453S, G allele leads to enzyme which catalyzes hydroxylation of estradiol more efficiently (Hanna et al. 2000) 19% A/A 452/467 1.00 A/G 202/187 0.89 (0.68-1.18) G/G 26/22 0.81 (0.40-1.62) 0.342 CYP1B1 rs1056836 L432V, G allele leads to enzyme with increased activity (Shimada et al. 1999) 41% C/C 224/220 1.00 C/G 339/320 1.00 (0.75-1.32) G/G 106/128 1.31 (0.91-1.88) 0.209 CYP1B1 rs1056827 A119S, T allele leads to enzyme which catalyzes hydroxylation of estradiol more efficiently (Hanna et al. 2000) 31% G/G 317/323 1.00 G/T 304/297 0.90 (0.70-1.17) T/T 57/55 0.85 (0.54-1.35) 0.362 continued gene ESR1 (interaction ORZ1.49, 95% CI 1.04-2.13, P interactionZ0.03). 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