Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

C L Pearce; A M Near; D J Van Den Berg; S J Ramus; A Gentry-Maharaj; U Menon; S A Gayther; A R Anderson; C K Edlund; A H Wu; X Chen; J Beesley; P M Webb; S K Holt; C Chen; J A Doherty; M A Rossing; A S Whittemore; V McGuire; R A DiCioccio; M T Goodman; G Lurie; M E Carney; L R Wilkens; R B Ness; K B Moysich; R Edwards; E Jennison; Susanne Krüger Kjær; E Hogdall; C K Hogdall; E L Goode; T A Sellers; R A Vierkant; J M Cunningham; J C Cunningham; J M Schildkraut; A Berchuck; P G Moorman; E S Iversen; D W Cramer; K L Terry; A F Vitonis; L Titus-Ernstoff; H Song; P D P Pharoah; A B Spurdle; H Anton-Culver; A Ziogas; W Brewster; Australian Cancer Study; Australian Ovarian Cancer Study Group

doi:10.1038/sj.bjc.6604820

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

C L Pearce, A M Near, D J Van Den Berg, S J Ramus, A Gentry-Maharaj, U Menon, S A Gayther, A R Anderson, C K Edlund, A H Wu, X Chen, J Beesley, P M Webb, S K Holt, C Chen, J A Doherty, M A Rossing, A S Whittemore, V McGuire, R A DiCioccioM T Goodman, G Lurie, M E Carney, L R Wilkens, R B Ness, K B Moysich, R Edwards, E Jennison, Susanne Krüger Kjær, E Hogdall, C K Hogdall, E L Goode, T A Sellers, R A Vierkant, J M Cunningham, J C Cunningham, J M Schildkraut, A Berchuck, P G Moorman, E S Iversen, D W Cramer, K L Terry, A F Vitonis, L Titus-Ernstoff, H Song, P D P Pharoah, A B Spurdle, H Anton-Culver, A Ziogas, W Brewster, Australian Cancer Study, Australian Ovarian Cancer Study Group

45 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Jan-27

Originalsprog	Engelsk
Tidsskrift	British Journal of Cancer
Vol/bind	100
Udgave nummer	2
Sider (fra-til)	412-20
Antal sider	8
ISSN	0007-0920
DOI	https://doi.org/10.1038/sj.bjc.6604820
Status	Udgivet - 2009

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Pearce, C. L., Near, A. M., Van Den Berg, D. J., Ramus, S. J., Gentry-Maharaj, A., Menon, U., Gayther, S. A., Anderson, A. R., Edlund, C. K., Wu, A. H., Chen, X., Beesley, J., Webb, P. M., Holt, S. K., Chen, C., Doherty, J. A., Rossing, M. A., Whittemore, A. S., McGuire, V., ... Australian Ovarian Cancer Study Group (2009). Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium. British Journal of Cancer, 100(2), 412-20. https://doi.org/10.1038/sj.bjc.6604820

Pearce, CL, Near, AM, Van Den Berg, DJ, Ramus, SJ, Gentry-Maharaj, A, Menon, U, Gayther, SA, Anderson, AR, Edlund, CK, Wu, AH, Chen, X, Beesley, J, Webb, PM, Holt, SK, Chen, C, Doherty, JA, Rossing, MA, Whittemore, AS, McGuire, V, DiCioccio, RA, Goodman, MT, Lurie, G, Carney, ME, Wilkens, LR, Ness, RB, Moysich, KB, Edwards, R, Jennison, E, Kjær, SK, Hogdall, E, Hogdall, CK, Goode, EL, Sellers, TA, Vierkant, RA, Cunningham, JM, Cunningham, JC, Schildkraut, JM, Berchuck, A, Moorman, PG, Iversen, ES, Cramer, DW, Terry, KL, Vitonis, AF, Titus-Ernstoff, L, Song, H, Pharoah, PDP, Spurdle, AB, Anton-Culver, H, Ziogas, A, Brewster, W, Australian Cancer Study & Australian Ovarian Cancer Study Group 2009, 'Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium', British Journal of Cancer, bind 100, nr. 2, s. 412-20. https://doi.org/10.1038/sj.bjc.6604820

@article{196b0d0072d911df928f000ea68e967b,

title = "Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium",

abstract = "The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.",

author = "Pearce, {C L} and Near, {A M} and {Van Den Berg}, {D J} and Ramus, {S J} and A Gentry-Maharaj and U Menon and Gayther, {S A} and Anderson, {A R} and Edlund, {C K} and Wu, {A H} and X Chen and J Beesley and Webb, {P M} and Holt, {S K} and C Chen and Doherty, {J A} and Rossing, {M A} and Whittemore, {A S} and V McGuire and DiCioccio, {R A} and Goodman, {M T} and G Lurie and Carney, {M E} and Wilkens, {L R} and Ness, {R B} and Moysich, {K B} and R Edwards and E Jennison and Kj{\ae}r, {Susanne Kr{\"u}ger} and E Hogdall and Hogdall, {C K} and Goode, {E L} and Sellers, {T A} and Vierkant, {R A} and Cunningham, {J M} and Cunningham, {J C} and Schildkraut, {J M} and A Berchuck and Moorman, {P G} and Iversen, {E S} and Cramer, {D W} and Terry, {K L} and Vitonis, {A F} and L Titus-Ernstoff and H Song and Pharoah, {P D P} and Spurdle, {A B} and H Anton-Culver and A Ziogas and W Brewster and {Australian Cancer Study} and {Australian Ovarian Cancer Study Group}",

note = "Keywords: Adult; Aged; Case-Control Studies; Cohort Studies; Cytochrome P-450 CYP3A; DNA Ligases; DNA-Binding Proteins; Female; Genetic Predisposition to Disease; Genotype; Heterozygote; Homozygote; Humans; Middle Aged; Neoplasm Invasiveness; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Risk Factors",

year = "2009",

doi = "10.1038/sj.bjc.6604820",

language = "English",

volume = "100",

pages = "412--20",

journal = "The British journal of cancer. Supplement",

issn = "0007-0920",

publisher = "nature publishing group",

number = "2",

}

TY - JOUR

T1 - Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

AU - Pearce, C L

AU - Near, A M

AU - Van Den Berg, D J

AU - Ramus, S J

AU - Gentry-Maharaj, A

AU - Menon, U

AU - Gayther, S A

AU - Anderson, A R

AU - Edlund, C K

AU - Wu, A H

AU - Chen, X

AU - Beesley, J

AU - Webb, P M

AU - Holt, S K

AU - Chen, C

AU - Doherty, J A

AU - Rossing, M A

AU - Whittemore, A S

AU - McGuire, V

AU - DiCioccio, R A

AU - Goodman, M T

AU - Lurie, G

AU - Carney, M E

AU - Wilkens, L R

AU - Ness, R B

AU - Moysich, K B

AU - Edwards, R

AU - Jennison, E

AU - Kjær, Susanne Krüger

AU - Hogdall, E

AU - Hogdall, C K

AU - Goode, E L

AU - Sellers, T A

AU - Vierkant, R A

AU - Cunningham, J M

AU - Cunningham, J C

AU - Schildkraut, J M

AU - Berchuck, A

AU - Moorman, P G

AU - Iversen, E S

AU - Cramer, D W

AU - Terry, K L

AU - Vitonis, A F

AU - Titus-Ernstoff, L

AU - Song, H

AU - Pharoah, P D P

AU - Spurdle, A B

AU - Anton-Culver, H

AU - Ziogas, A

AU - Brewster, W

AU - Australian Cancer Study

AU - Australian Ovarian Cancer Study Group

N1 - Keywords: Adult; Aged; Case-Control Studies; Cohort Studies; Cytochrome P-450 CYP3A; DNA Ligases; DNA-Binding Proteins; Female; Genetic Predisposition to Disease; Genotype; Heterozygote; Homozygote; Humans; Middle Aged; Neoplasm Invasiveness; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Risk Factors

PY - 2009

Y1 - 2009

N2 - The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

AB - The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

U2 - 10.1038/sj.bjc.6604820

DO - 10.1038/sj.bjc.6604820

M3 - Journal article

C2 - 19127255

SN - 0007-0920

VL - 100

SP - 412

EP - 420

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

IS - 2

ER -

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

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