Abstract
As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well-known ovarian cancer risk factors and their interactions with 28 genome-wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case–control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10−4). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46–0.60) compared to 0.71 (95%CI = 0.66–0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1–5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene–environment analysis in ovarian cancer.
| Original language | English (US) |
|---|---|
| Journal | International Journal of Cancer |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
Fingerprint
Keywords
- additive interaction
- G × E
- genetics
- ovarian cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
A comprehensive gene–environment interaction analysis in Ovarian Cancer using genome-wide significant common variants. / Kim, Sehee; Wang, Miao; Tyrer, Jonathan P.; Jensen, Allan; Wiensch, Ashley; Liu, Gang; Lee, Alice W.; Ness, Roberta B.; Salvatore, Maxwell; Tworoger, Shelley S.; Whittemore, Alice S.; Anton-Culver, Hoda; Sieh, Weiva; Olson, Sara H.; Berchuck, Andrew; Goode, Ellen L; Goodman, Marc T.; Doherty, Jennifer Anne; Chenevix-Trench, Georgia; Rossing, Mary Anne; Webb, Penelope M.; Giles, Graham G.; Terry, Kathryn L.; Ziogas, Argyrios; Fortner, Renée T.; Menon, Usha; Gayther, Simon A.; Wu, Anna H.; Song, Honglin; Brooks-Wilson, Angela; Bandera, Elisa V.; Cook, Linda S.; Cramer, Daniel W.; Milne, Roger L.; Winham, Stacey J; Kjaer, Susanne K.; Modugno, Francesmary; Thompson, Pamela J.; Chang-Claude, Jenny; Harris, Holly R.; Schildkraut, Joellen M.; Le, Nhu D.; Wentzensen, Nico; Trabert, Britton; Høgdall, Estrid; Huntsman, David; Pike, Malcolm C.; Pharoah, Paul D.P.; Pearce, Celeste Leigh; Mukherjee, Bhramar.
In: International Journal of Cancer, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A comprehensive gene–environment interaction analysis in Ovarian Cancer using genome-wide significant common variants
AU - Kim, Sehee
AU - Wang, Miao
AU - Tyrer, Jonathan P.
AU - Jensen, Allan
AU - Wiensch, Ashley
AU - Liu, Gang
AU - Lee, Alice W.
AU - Ness, Roberta B.
AU - Salvatore, Maxwell
AU - Tworoger, Shelley S.
AU - Whittemore, Alice S.
AU - Anton-Culver, Hoda
AU - Sieh, Weiva
AU - Olson, Sara H.
AU - Berchuck, Andrew
AU - Goode, Ellen L
AU - Goodman, Marc T.
AU - Doherty, Jennifer Anne
AU - Chenevix-Trench, Georgia
AU - Rossing, Mary Anne
AU - Webb, Penelope M.
AU - Giles, Graham G.
AU - Terry, Kathryn L.
AU - Ziogas, Argyrios
AU - Fortner, Renée T.
AU - Menon, Usha
AU - Gayther, Simon A.
AU - Wu, Anna H.
AU - Song, Honglin
AU - Brooks-Wilson, Angela
AU - Bandera, Elisa V.
AU - Cook, Linda S.
AU - Cramer, Daniel W.
AU - Milne, Roger L.
AU - Winham, Stacey J
AU - Kjaer, Susanne K.
AU - Modugno, Francesmary
AU - Thompson, Pamela J.
AU - Chang-Claude, Jenny
AU - Harris, Holly R.
AU - Schildkraut, Joellen M.
AU - Le, Nhu D.
AU - Wentzensen, Nico
AU - Trabert, Britton
AU - Høgdall, Estrid
AU - Huntsman, David
AU - Pike, Malcolm C.
AU - Pharoah, Paul D.P.
AU - Pearce, Celeste Leigh
AU - Mukherjee, Bhramar
PY - 2019/1/1
Y1 - 2019/1/1
N2 - As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well-known ovarian cancer risk factors and their interactions with 28 genome-wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case–control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10−4). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46–0.60) compared to 0.71 (95%CI = 0.66–0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1–5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene–environment analysis in ovarian cancer.
AB - As a follow-up to genome-wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well-known ovarian cancer risk factors and their interactions with 28 genome-wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case–control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10−4). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46–0.60) compared to 0.71 (95%CI = 0.66–0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1–5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene–environment analysis in ovarian cancer.
KW - additive interaction
KW - G × E
KW - genetics
KW - ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85060352233&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060352233&partnerID=8YFLogxK
U2 - 10.1002/ijc.32029
DO - 10.1002/ijc.32029
M3 - Article
C2 - 30499236
AN - SCOPUS:85060352233
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
ER -