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1. Pre-diagnosis tea and coffee consumption and survival after a diagnosis of ovarian cancer: results from the Ovarian Cancer Association Consortium.

Author

Nagle, CM, Ibiebele, TI, Bandera, EV, Cramer, D, Doherty, JA, Giles, GG, Goodman, MT, Hanley, GE, Harris, HR, Jensen, A, Kjaer, SK, Lee, AW, Milne, RL, Qin, B, Richardson, J, Sasamoto, N, Sieh, W, Terry, KL, Titus, L, Trabert, B, Wentzensen, N, Wu, AH, Berchuck, A, Pike, M, Pearce, CL, Webb, PM, Nagle, CM, Ibiebele, TI, Bandera, EV, Cramer, D, Doherty, JA, Giles, GG, Goodman, MT, Hanley, GE, Harris, HR, Jensen, A, Kjaer, SK, Lee, AW, Milne, RL, Qin, B, Richardson, J, Sasamoto, N, Sieh, W, Terry, KL, Titus, L, Trabert, B, Wentzensen, N, Wu, AH, Berchuck, A, Pike, M, Pearce, CL, and Webb, PM

Abstract

BACKGROUND: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain. METHODS: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Compared with women who did not drink any green tea, consumption of one or more cups/day was associated with better overall survival (aHR = 0.84, 95% CI 0.71-1.00, p-trend = 0.04). A similar association was seen for ovarian cancer-specific survival in five studies with this information (aHR = 0.81, 0.66-0.99, p-trend = 0.045). There was no consistent variation between subgroups defined by clinical or lifestyle characteristics and adjustment for other aspects of lifestyle did not appreciably alter the estimates. We found no evidence of an association between coffee, black or herbal tea, or caffeine intake and survival. CONCLUSION: The observed association with green tea consumption before diagnosis raises the possibility that consumption after diagnosis might improve patient outcomes.

Published
2024

2. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

Author

Amankwah, EK, Lin, HY, Tyrer, JP, Lawrenson, K, Dennis, J, Chornokur, G, Aben, KKH, Anton-Culver, H, Antonenkova, N, Bruinsma, F, Bandera, EV, Bean, YT, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bunker, CH, Butzow, R, Campbell, IG, Carty, K, Chen, Z, Chen, YA, Chang-Claude, J, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, du Bois, A, Despierre, E, Dicks, E, Doherty, JA, Dörk, T, Dürst, M, Easton, DF, Eccles, DM, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, YT, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goodman, MT, Gronwald, J, Harrington, P, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, CK, Hogdall, E, Hosono, S, Iversen, ES, Jakubowska, A, Jensen, A, Ji, BT, Karlan, BY, Jim, H, Kellar, M, Kiemeney, LA, Krakstad, C, Kjaer, SK, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lim, BK, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, Mcguire, V, Mclaughlin, JR, Mcneish, I, Menon, U, Milne, RL, Modugno, F, Moysich, KB, Ness, RB, Nevanlinna, H, Eilber, U, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, and Weber, RP

Subjects
Epidemiology, Public Health and Health Services, Genetics
Abstract

Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value

Published
2015

3. Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis

Author

Fu, Z, Brooks, MM, Irvin, S, Jordan, S, Aben, KKH, Anton-Culver, H, Bandera, E, Beckmann, MW, Berchuck, A, Brooks-Wilson, A, Chang-Claude, J, Cook, LS, Cramer, DW, Cushing-Haugen, KL, Doherty, JA, Ekici, AB, Fasching, PA, Fortner, RT, Gayther, SA, Gentry-Maharaj, A, Giles, GG, Goode, EL, Goodman, MT, Harris, HR, Hein, A, Kaaks, R, Kiemeney, LA, Koebel, M, Kotsopoulos, J, Le, ND, Lee, AW, Matsuo, K, McGuire, V, McLaughlin, JR, Menon, U, Milne, RL, Moysich, KB, Pearce, CL, Pike, MC, Qin, B, Ramus, SJ, Riggan, MJ, Rothstein, JH, Schildkraut, JM, Sieh, W, Sutphen, R, Terry, KL, Thompson, PJ, Titus, L, van Altena, AM, White, E, Whittemore, AS, Wu, AH, Zheng, W, Ziogas, A, Taylor, SE, Tang, L, Songer, T, Wentzensen, N, Webb, PM, Risch, HA, Modugno, F, Fu, Z, Brooks, MM, Irvin, S, Jordan, S, Aben, KKH, Anton-Culver, H, Bandera, E, Beckmann, MW, Berchuck, A, Brooks-Wilson, A, Chang-Claude, J, Cook, LS, Cramer, DW, Cushing-Haugen, KL, Doherty, JA, Ekici, AB, Fasching, PA, Fortner, RT, Gayther, SA, Gentry-Maharaj, A, Giles, GG, Goode, EL, Goodman, MT, Harris, HR, Hein, A, Kaaks, R, Kiemeney, LA, Koebel, M, Kotsopoulos, J, Le, ND, Lee, AW, Matsuo, K, McGuire, V, McLaughlin, JR, Menon, U, Milne, RL, Moysich, KB, Pearce, CL, Pike, MC, Qin, B, Ramus, SJ, Riggan, MJ, Rothstein, JH, Schildkraut, JM, Sieh, W, Sutphen, R, Terry, KL, Thompson, PJ, Titus, L, van Altena, AM, White, E, Whittemore, AS, Wu, AH, Zheng, W, Ziogas, A, Taylor, SE, Tang, L, Songer, T, Wentzensen, N, Webb, PM, Risch, HA, and Modugno, F

Abstract

BACKGROUND: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. METHODS: LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. RESULTS: LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. CONCLUSIONS: LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.

Published
2023

4. Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery

Author

Phung, MT, Webb, PM, DeFazio, A, Fereday, S, Lee, AW, Bowtell, DDL, Fasching, PA, Goode, EL, Goodman, MT, Karlan, BY, Lester, J, Matsuo, K, Modugno, F, Brenton, JD, Van Gorp, T, Pharoah, PDP, Schildkraut, JM, McLean, K, Meza, R, Mukherjee, B, Richardson, J, Grout, B, Chase, A, Deurloo, CM, Terry, KL, Hanley, GE, Pike, MC, Berchuck, A, Ramus, SJ, Pearce, CL, Ovarian, CAC, Phung, MT, Webb, PM, DeFazio, A, Fereday, S, Lee, AW, Bowtell, DDL, Fasching, PA, Goode, EL, Goodman, MT, Karlan, BY, Lester, J, Matsuo, K, Modugno, F, Brenton, JD, Van Gorp, T, Pharoah, PDP, Schildkraut, JM, McLean, K, Meza, R, Mukherjee, B, Richardson, J, Grout, B, Chase, A, Deurloo, CM, Terry, KL, Hanley, GE, Pike, MC, Berchuck, A, Ramus, SJ, Pearce, CL, and Ovarian, CAC

Abstract

OBJECTIVE: The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery. METHODS: This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS. RESULTS: Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53). CONCLUSIONS: The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Published
2023

5. Endometriosis and menopausal hormone therapy impact the hysterectomy-ovarian cancer association.

Author

Khoja, L, Weber, RP, Australian Ovarian Cancer Study Group, Webb, PM, Jordan, SJ, Muthukumar, A, Chang-Claude, J, Fortner, RT, Jensen, A, Kjaer, SK, Risch, H, Doherty, JA, Harris, HR, Goodman, MT, Modugno, F, Moysich, K, Berchuck, A, Schildkraut, JM, Cramer, D, Terry, KL, Anton-Culver, H, Ziogas, A, Phung, MT, Hanley, GE, Wu, AH, Mukherjee, B, McLean, K, Cho, K, Pike, MC, Pearce, CL, Lee, AW, Khoja, L, Weber, RP, Australian Ovarian Cancer Study Group, Webb, PM, Jordan, SJ, Muthukumar, A, Chang-Claude, J, Fortner, RT, Jensen, A, Kjaer, SK, Risch, H, Doherty, JA, Harris, HR, Goodman, MT, Modugno, F, Moysich, K, Berchuck, A, Schildkraut, JM, Cramer, D, Terry, KL, Anton-Culver, H, Ziogas, A, Phung, MT, Hanley, GE, Wu, AH, Mukherjee, B, McLean, K, Cho, K, Pike, MC, Pearce, CL, and Lee, AW

Abstract

OBJECTIVE: To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. METHODS: We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99). CONCLUSIONS: The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

Published
2022

6. Radiotherapy for parapharyngeal space tumors

Author

Mendenhall, WM, Strojan, P, Beitler, JJ, Langendijk, JA, Suarez, C, Lee, AW, Rinaldo, A, Rodrigo, JP, Smee, R, Eisbruch, A, Harrison, LB, Corry, J, Ferlito, A, Mendenhall, WM, Strojan, P, Beitler, JJ, Langendijk, JA, Suarez, C, Lee, AW, Rinaldo, A, Rodrigo, JP, Smee, R, Eisbruch, A, Harrison, LB, Corry, J, and Ferlito, A

Abstract

A wide variety of tumors, both benign and malignant, occur in the parapharyngeal space. Depending on histology and extent, treatment may include surgery and/or radiotherapy (RT). Herein we discuss the role of RT in the management of some of the more commonly encountered neoplasms, including salivary gland tumors, paragangliomas, schwannomas, and soft-tissue sarcomas.

Published
2019

7. A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants

Author

Kim, S, Wang, M, Tyrer, JP, Jensen, A, Wiensch, A, Liu, G, Lee, AW, Ness, RB, Salvatore, M, Tworoger, SS, Whittemore, AS, Anton-Culver, H, Sieh, W, Olson, SH, Berchuck, A, Goode, EL, Goodman, MT, Doherty, JA, Chenevix-Trench, G, Rossing, MA, Webb, PM, Giles, GG, Terry, KL, Ziogas, A, Fortner, RT, Menon, U, Gayther, SA, Wu, AH, Song, H, Brooks-Wilson, A, Bandera, E, Cook, LS, Cramer, DW, Milne, RL, Winham, SJ, Kjaer, SK, Modugno, F, Thompson, PJ, Chang-Claude, J, Harris, HR, Schildkraut, JM, Le, ND, Wentzensen, N, Trabert, B, Hogdall, E, Huntsman, D, Pike, MC, Pharoah, PDP, Pearce, CL, Mukherjee, B, Kim, S, Wang, M, Tyrer, JP, Jensen, A, Wiensch, A, Liu, G, Lee, AW, Ness, RB, Salvatore, M, Tworoger, SS, Whittemore, AS, Anton-Culver, H, Sieh, W, Olson, SH, Berchuck, A, Goode, EL, Goodman, MT, Doherty, JA, Chenevix-Trench, G, Rossing, MA, Webb, PM, Giles, GG, Terry, KL, Ziogas, A, Fortner, RT, Menon, U, Gayther, SA, Wu, AH, Song, H, Brooks-Wilson, A, Bandera, E, Cook, LS, Cramer, DW, Milne, RL, Winham, SJ, Kjaer, SK, Modugno, F, Thompson, PJ, Chang-Claude, J, Harris, HR, Schildkraut, JM, Le, ND, Wentzensen, N, Trabert, B, Hogdall, E, Huntsman, D, Pike, MC, Pharoah, PDP, Pearce, CL, and Mukherjee, B

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.

Published
2019

8. rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology

Author

Kelemen, LE, Earp, M, Fridley, BL, Chenevix-Trench, G, Fasching, PA, Beckmann, MW, Ekici, AB, Hein, A, Lambrechts, D, Lambrechts, S, Van Nieuwenhuysen, E, Vergote, I, Rossing, MA, Doherty, JA, Chang-Claude, J, Behrens, S, Moysich, KB, Cannioto, R, Lele, S, Odunsi, K, Goodman, MT, Shvetsov, YB, Thompson, PJ, Wilkens, LR, Doerk, T, Antonenkova, N, Bogdanova, N, Hillemanns, P, Runnebaum, IB, du Bois, A, Harter, P, Heitz, F, Schwaab, I, Butzow, R, Pelttari, LM, Nevanlinna, H, Modugno, F, Edwards, RP, Kelley, JL, Ness, RB, Karlan, BY, Lester, J, Orsulic, S, Walsh, C, Kjaer, SK, Jensen, A, Cunningham, JM, Vierkant, RA, Giles, GG, Bruinsma, F, Southey, MC, Hildebrandt, MAT, Liang, D, Lu, K, Wu, X, Sellers, TA, Levine, DA, Schildkraut, JM, Iversen, ES, Terry, KL, Cramer, DW, Tworoger, SS, Poole, EM, Bandera, EV, Olson, SH, Orlow, I, Thomsen, LCV, Bjorge, L, Krakstad, C, Tangen, IL, Kiemeney, LA, Aben, KKH, Massuger, LFAG, van Altena, AM, Pejovic, T, Bean, Y, Kellar, M, Cook, LS, Le, ND, Brooks-Wilson, A, Gronwald, J, Cybulski, C, Jakubowska, A, Lubinski, J, Wentzensen, N, Brinton, LA, Lissowska, J, Hogdall, E, Engelholm, SA, Hogdall, C, Lundvall, L, Nedergaard, L, Pharoah, PDP, Dicks, E, Song, H, Tyrer, JP, McNeish, I, Siddiqui, N, Carty, K, Glasspool, R, Paul, J, Campbell, IG, Eccles, D, Whittemore, AS, McGuire, V, Rothstein, JH, Sieh, W, Narod, SA, Phelan, CM, McLaughlin, JR, Risch, HA, Anton-Culver, H, Ziogas, A, Menon, U, Gayther, SA, Gentry-Maharaj, A, Ramus, SJ, Wu, AH, Pearce, CL, Lee, AW, Pike, MC, Kupryjanczyk, J, Podgorska, A, Plisiecka-Halasa, J, Sawicki, W, Goode, EL, Berchuck, A, Kelemen, LE, Earp, M, Fridley, BL, Chenevix-Trench, G, Fasching, PA, Beckmann, MW, Ekici, AB, Hein, A, Lambrechts, D, Lambrechts, S, Van Nieuwenhuysen, E, Vergote, I, Rossing, MA, Doherty, JA, Chang-Claude, J, Behrens, S, Moysich, KB, Cannioto, R, Lele, S, Odunsi, K, Goodman, MT, Shvetsov, YB, Thompson, PJ, Wilkens, LR, Doerk, T, Antonenkova, N, Bogdanova, N, Hillemanns, P, Runnebaum, IB, du Bois, A, Harter, P, Heitz, F, Schwaab, I, Butzow, R, Pelttari, LM, Nevanlinna, H, Modugno, F, Edwards, RP, Kelley, JL, Ness, RB, Karlan, BY, Lester, J, Orsulic, S, Walsh, C, Kjaer, SK, Jensen, A, Cunningham, JM, Vierkant, RA, Giles, GG, Bruinsma, F, Southey, MC, Hildebrandt, MAT, Liang, D, Lu, K, Wu, X, Sellers, TA, Levine, DA, Schildkraut, JM, Iversen, ES, Terry, KL, Cramer, DW, Tworoger, SS, Poole, EM, Bandera, EV, Olson, SH, Orlow, I, Thomsen, LCV, Bjorge, L, Krakstad, C, Tangen, IL, Kiemeney, LA, Aben, KKH, Massuger, LFAG, van Altena, AM, Pejovic, T, Bean, Y, Kellar, M, Cook, LS, Le, ND, Brooks-Wilson, A, Gronwald, J, Cybulski, C, Jakubowska, A, Lubinski, J, Wentzensen, N, Brinton, LA, Lissowska, J, Hogdall, E, Engelholm, SA, Hogdall, C, Lundvall, L, Nedergaard, L, Pharoah, PDP, Dicks, E, Song, H, Tyrer, JP, McNeish, I, Siddiqui, N, Carty, K, Glasspool, R, Paul, J, Campbell, IG, Eccles, D, Whittemore, AS, McGuire, V, Rothstein, JH, Sieh, W, Narod, SA, Phelan, CM, McLaughlin, JR, Risch, HA, Anton-Culver, H, Ziogas, A, Menon, U, Gayther, SA, Gentry-Maharaj, A, Ramus, SJ, Wu, AH, Pearce, CL, Lee, AW, Pike, MC, Kupryjanczyk, J, Podgorska, A, Plisiecka-Halasa, J, Sawicki, W, Goode, EL, and Berchuck, A

Abstract

Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3' gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97⁻1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03⁻1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10-28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.

Published
2018

9. Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies

Author

Praestegaard, C, Jensen, A, Jensen, SM, Nielsen, TSS, Webb, PM, Nagle, CM, DeFazio, A, Hogdall, E, Rossing, MA, Doherty, JA, Wicklund, KG, Goodman, MT, Modugno, F, Moysich, K, Ness, RB, Edwards, R, Matsuo, K, Hosono, S, Goode, EL, Winham, SJ, Fridley, BL, Cramer, DW, Terry, KL, Schildkraut, JM, Berchuck, A, Bandera, EV, Paddock, LE, Massuger, LF, Wentzensen, N, Pharoah, P, Song, H, Whittemore, A, McGuire, V, Sieh, W, Rothstein, J, Anton-Culver, H, Ziogas, A, Menon, U, Gayther, SA, Ramus, SJ, Gentry-Maharaj, A, Wu, AH, Pearce, CL, Pike, M, Lee, AW, Sutphen, R, Chang-Claude, J, Risch, HA, Kjaer, SK, Praestegaard, C, Jensen, A, Jensen, SM, Nielsen, TSS, Webb, PM, Nagle, CM, DeFazio, A, Hogdall, E, Rossing, MA, Doherty, JA, Wicklund, KG, Goodman, MT, Modugno, F, Moysich, K, Ness, RB, Edwards, R, Matsuo, K, Hosono, S, Goode, EL, Winham, SJ, Fridley, BL, Cramer, DW, Terry, KL, Schildkraut, JM, Berchuck, A, Bandera, EV, Paddock, LE, Massuger, LF, Wentzensen, N, Pharoah, P, Song, H, Whittemore, A, McGuire, V, Sieh, W, Rothstein, J, Anton-Culver, H, Ziogas, A, Menon, U, Gayther, SA, Ramus, SJ, Gentry-Maharaj, A, Wu, AH, Pearce, CL, Pike, M, Lee, AW, Sutphen, R, Chang-Claude, J, Risch, HA, and Kjaer, SK

Abstract

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08-1.28) and former smokers (pHR = 1.10, 95% CI: 1.02-1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01-3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00-1.23; former smoking: pHR = 1.12, 95% CI: 1.04-1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis.

Published
2017

10. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

Author

Hampras, SS, Sucheston-Campbell, LE, Cannioto, R, Chang-Claude, J, Modugno, F, Dörk, T, Hillemanns, P, Preus, L, Knutson, KL, Wallace, PK, Hong, CC, Friel, G, Davis, W, Nesline, M, Pearce, CL, Kelemen, LE, Goodman, MT, Bandera, EV, Terry, KL, Schoof, N, Eng, KH, Clay, A, Singh, PK, Joseph, JM, Aben, KKH, Anton-Culver, H, Antonenkova, N, Baker, H, Bean, Y, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bruinsma, F, Butzow, R, Campbell, IG, Carty, K, Cook, LS, Cramer, DW, Cybulski, C, Dansonka-Mieszkowska, A, Dennis, J, Despierre, E, Dicks, E, Doherty, JA, du Bois, A, Dürst, M, Easton, D, Eccles, D, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, YT, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Gronwald, J, Harrington, P, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hogdall, C, Hogdall, E, Hosono, S, Iversen, ES, Jakubowska, A, Jensen, A, Ji, BT, Karlan, BY, Kellar, M, Kelley, JL, Kiemeney, LA, Klapdor, R, Kolomeyevskaya, N, Krakstad, C, Kjaer, SK, Kruszka, B, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lissowska, J, Liu, S, and Lu, K

Subjects
endocrine system diseases, female genital diseases and pregnancy complications
Abstract

Background: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. Methods: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. Results: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). Conclusions: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

Published
2016

11. Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk

Author

Chornokur, G, Lin, HY, Tyrer, JP, Lawrenson, K, Dennis, J, Amankwah, EK, Qu, X, Tsai, YY, Jim, HSL, Chen, Z, Chen, AY, Permuth-Wey, J, Aben, KKH, Anton-Culver, H, Antonenkova, N, Bruinsma, F, Bandera, EV, Bean, YT, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bunker, CH, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, Du Bois, A, Despierre, E, Dicks, E, Doherty, JA, Dörk, T, Dürst, M, Easton, DF, Eccles, DM, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, YT, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goodman, MT, Gronwald, J, Harrington, P, Harter, P, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, CK, Hogdall, E, Hosono, S, Jakubowska, A, Jensen, A, Ji, BT, Karlan, BY, Kelemen, LE, Kellar, M, Kiemeney, LA, Krakstad, C, Kjaer, SK, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, and Lester, J

Abstract

© 2015 Chornokur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q-4). Conclusion: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.

Published
2015

12. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study

Author

Lee, AW, Tyrer, JP, Doherty, JA, Stram, DA, Kupryjanczyk, J, Dansonka-Mieszkowska, A, Plisiecka-Halasa, J, Spiewankiewicz, B, Myers, EJ, Chenevix-Trench, G, Fasching, PA, Beckmann, MW, Ekici, AB, Hein, A, Vergote, I, Van Nieuwenhuysen, E, Lambrechts, D, Wicklund, KG, Eilber, U, Wang-Gohrke, S, Chang-Claude, J, Rudolph, A, Sucheston-Campbell, L, Odunsi, K, Moysich, KB, Shvetsov, YB, Thompson, PJ, Goodman, MT, Wilkens, LR, Dörk, T, Hillemanns, P, Dürst, M, Runnebaum, IB, Bogdanova, N, Pelttari, LM, Nevanlinna, H, Leminen, A, Edwards, RP, Kelley, JL, Harter, P, Schwaab, I, Heitz, F, Du Bois, A, Orsulic, S, Lester, J, Walsh, C, Karlan, BY, Hogdall, E, Kjaer, SK, Jensen, A, Vierkant, RA, Cunningham, JM, Goode, EL, Fridley, BL, Southey, MC, Giles, GG, Bruinsma, F, Wu, X, Hildebrandt, MAT, Lu, K, Liang, D, Bisogna, M, Levine, DA, Weber, RP, Schildkraut, JM, Iversen, ES, Berchuck, A, Terry, KL, Cramer, DW, Tworoger, SS, Poole, EM, Olson, SH, Orlow, I, Bandera, EV, Bjorge, L, Tangen, IL, Salvesen, HB, Krakstad, C, and Massuger, LFAG

Subjects
endocrine system
Abstract

© 2014 Elsevier Inc. All rights reserved. Objective: Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. Methods: Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. Results: We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p = 0.045, mucinous), LHCGR (p = 0.046, high-grade serous), GNRH (p = 0.041, high-grade serous), and FSHB (p = 0.036, overall invasive). There was also suggestive evidence for INHA (p = 0.060, overall invasive). Conclusions: Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available.

Published
2015

13. Network-based integration of GWAS and gene expression identifies a HOX-centric network associated with serous ovarian cancer risk

Author

Kar, SP, Tyrer, JP, Li, Q, Lawrenson, K, Aben, KKH, Anton-Culver, H, Antonenkova, N, Chenevix-Trench, G, Baker, H, Bandera, EV, Bean, YT, Beckmann, MW, Berchuck, A, Bisogna, M, Bjørge, L, Bogdanova, N, Brinton, L, Brooks-Wilson, A, Butzow, R, Campbell, I, Carty, K, Chang-Claude, J, Chen, YA, Chen, Z, Cook, LS, Cramer, D, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, Dennis, J, Dicks, E, Doherty, JA, Dörk, T, Du Bois, A, Dürst, M, Eccles, D, Easton, DF, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, YT, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goode, EL, Goodman, MT, Grownwald, J, Harrington, P, Harter, P, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, E, Hogdall, CK, Hosono, S, Iversen, ES, Jakubowska, A, Paul, J, Jensen, A, Ji, BT, Karlan, BY, Kjaer, SK, Kelemen, LE, Kellar, M, Kelley, J, Kiemeney, LA, Krakstad, C, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, and Liang, D

Subjects
endocrine system diseases, female genital diseases and pregnancy complications
Abstract

© 2015 American Association for Cancer Research. Background: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. Methods: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Results: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. Conclusion: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Impact: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.

Published
2015

14. A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer

Author

Lee, AW, Bomkamp, A, Bandera, EV, Jensen, A, Ramus, SJ, Goodman, MT, Rossing, MA, Modugno, F, Moysich, KB, Chang-Claude, J, Rudolph, A, Gentry-Maharaj, A, Terry, KL, Gayther, SA, Cramer, DW, Doherty, JA, Schildkraut, JM, Kjaer, SK, Ness, RB, Menon, U, Berchuck, A, Mukherjee, B, Roman, L, Pharoah, PD, Chenevix-Trench, G, Olson, S, Hogdall, E, Wu, AH, Pike, MC, Stram, DO, Pearce, CL, Lee, AW, Bomkamp, A, Bandera, EV, Jensen, A, Ramus, SJ, Goodman, MT, Rossing, MA, Modugno, F, Moysich, KB, Chang-Claude, J, Rudolph, A, Gentry-Maharaj, A, Terry, KL, Gayther, SA, Cramer, DW, Doherty, JA, Schildkraut, JM, Kjaer, SK, Ness, RB, Menon, U, Berchuck, A, Mukherjee, B, Roman, L, Pharoah, PD, Chenevix-Trench, G, Olson, S, Hogdall, E, Wu, AH, Pike, MC, Stram, DO, and Pearce, CL

Abstract

Menopausal estrogen-alone therapy (ET) is a well-established risk factor for serous and endometrioid ovarian cancer. Genetics also plays a role in ovarian cancer, which is partly attributable to 18 confirmed ovarian cancer susceptibility loci identified by genome-wide association studies. The interplay among these loci, ET use and ovarian cancer risk has yet to be evaluated. We analyzed data from 1,414 serous cases, 337 endometrioid cases and 4,051 controls across 10 case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Conditional logistic regression was used to determine the association between the confirmed susceptibility variants and risk of serous and endometrioid ovarian cancer among ET users and non-users separately and to test for statistical interaction. A splicing variant in TERT, rs10069690, showed a statistically significant interaction with ET use for risk of serous ovarian cancer (pint = 0.013). ET users carrying the T allele had a 51% increased risk of disease (OR = 1.51, 95% CI 1.19-1.91), which was stronger for long-term ET users of 10+ years (OR = 1.85, 95% CI 1.28-2.66, pint = 0.034). Non-users showed essentially no association (OR = 1.08, 95% CI 0.96-1.21). Two additional genomic regions harboring rs7207826 (C allele) and rs56318008 (T allele) also had significant interactions with ET use for the endometrioid histotype (pint = 0.021 and pint = 0.037, respectively). Hence, three confirmed susceptibility variants were identified whose associations with ovarian cancer risk are modified by ET exposure; follow-up is warranted given that these interactions are not adjusted for multiple comparisons. These findings, if validated, may elucidate the mechanism of action of these loci.

Published
2016

15. Application of Artificial Intelligence for Nasopharyngeal Carcinoma Management – A Systematic Review

Author

Ng WT, But B, Choi HCW, de Bree R, Lee AWM, Lee VHF, López F, Mäkitie AA, Rodrigo JP, Saba NF, Tsang RKY, and Ferlito A

Subjects
machine learning, neural network, deep learning, prognosis, diagnosis, auto contouring, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Wai Tong Ng,1,2 Barton But,2 Horace CW Choi,3 Remco de Bree,4 Anne WM Lee,1,2 Victor HF Lee,1,2 Fernando López,5,6 Antti A Mäkitie,7– 9 Juan P Rodrigo,5,6 Nabil F Saba,10 Raymond KY Tsang,11 Alfio Ferlito12 1Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; 3Department of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; 4Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; 5Department of Otolaryngology, Hospital Universitario Central de Asturias (HUCA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, 33011, Spain; 6Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Madrid, 28029, Spain; 7Department of Otorhinolaryngology - Head and Neck Surgery, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 8Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 9Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; 10Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA; 11Division of Otorhinolaryngology, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 12Coordinator of the International Head and Neck Scientific Group, Padua, ItalyCorrespondence: Barton ButDepartment of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of ChinaTel +852 2255 4352Fax +852 2872 6426Email bbut@hku.hkIntroduction: Nasopharyngeal carcinoma (NPC) is endemic to Eastern and South-Eastern Asia, and, in 2020, 77% of global cases were diagnosed in these regions. Apart from its distinct epidemiology, the natural behavior, treatment, and prognosis are different from other head and neck cancers. With the growing trend of artificial intelligence (AI), especially deep learning (DL), in head and neck cancer care, we sought to explore the unique clinical application and implementation direction of AI in the management of NPC.Methods: The search protocol was performed to collect publications using AI, machine learning (ML) and DL in NPC management from PubMed, Scopus and Embase. The articles were filtered using inclusion and exclusion criteria, and the quality of the papers was assessed. Data were extracted from the finalized articles.Results: A total of 78 articles were reviewed after removing duplicates and papers that did not meet the inclusion and exclusion criteria. After quality assessment, 60 papers were included in the current study. There were four main types of applications, which were auto-contouring, diagnosis, prognosis, and miscellaneous applications (especially on radiotherapy planning). The different forms of convolutional neural networks (CNNs) accounted for the majority of DL algorithms used, while the artificial neural network (ANN) was the most frequent ML model implemented.Conclusion: There is an overall positive impact identified from AI implementation in the management of NPC. With improving AI algorithms, we envisage AI will be available as a routine application in a clinical setting soon.Keywords: machine learning, neural network, deep learning, prognosis, diagnosis, auto contouring

Published
2022

16. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

Author

Agoulnik, IU, Chornokur, G, Lin, H-Y, Tyrer, JP, Lawrenson, K, Dennis, J, Amankwah, EK, Qu, X, Tsai, Y-Y, Jim, HSL, Chen, Z, Chen, AY, Permuth-Wey, J, Aben, KKH, Anton-Culver, H, Antonenkova, N, Bruinsma, F, Bandera, EV, Bean, YT, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bunker, CH, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, du Bois, A, Despierre, E, Dicks, E, Doherty, JA, Dork, T, Durst, M, Easton, DF, Eccles, DM, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goodman, MT, Gronwald, J, Harrington, P, Harter, P, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, CK, Hogdall, E, Hosono, S, Jakubowska, A, Jensen, A, Ji, B-T, Karlan, BY, Kelemen, LE, Kellar, M, Kiemeney, LA, Krakstad, C, Kjaer, SK, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lim, BK, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, McNeish, I, Menon, U, Milne, RL, Modugno, F, Moysich, KB, Ness, RB, Nevanlinna, H, Eilber, U, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Weber, RP, Paul, J, Pearce, CL, Pejovic, T, Pelttari, LM, Pike, MC, Poole, EM, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schernhammer, E, Schwaab, I, Shu, X-O, Shvetsov, YB, Siddiqui, N, Sieh, W, Song, H, Southey, MC, Spiewankiewicz, B, Sucheston, L, Teo, S-H, Terry, KL, Thompson, PJ, Thomsen, L, Tangen, IL, Tworoger, SS, van Altena, AM, Vierkant, RA, Vergote, I, Walsh, CS, Wang-Gohrke, S, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, LR, Wu, AH, Wu, X, Woo, Y-L, Yang, H, Zheng, W, Ziogas, A, Hasmad, HN, Berchuck, A, Iversen, ES, Schildkraut, JM, Ramus, SJ, Goode, EL, Monteiro, ANA, Gayther, SA, Narod, SA, Pharoah, PP, Sellers, TA, Phelan, CM, Agoulnik, IU, Chornokur, G, Lin, H-Y, Tyrer, JP, Lawrenson, K, Dennis, J, Amankwah, EK, Qu, X, Tsai, Y-Y, Jim, HSL, Chen, Z, Chen, AY, Permuth-Wey, J, Aben, KKH, Anton-Culver, H, Antonenkova, N, Bruinsma, F, Bandera, EV, Bean, YT, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bunker, CH, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, du Bois, A, Despierre, E, Dicks, E, Doherty, JA, Dork, T, Durst, M, Easton, DF, Eccles, DM, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goodman, MT, Gronwald, J, Harrington, P, Harter, P, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, CK, Hogdall, E, Hosono, S, Jakubowska, A, Jensen, A, Ji, B-T, Karlan, BY, Kelemen, LE, Kellar, M, Kiemeney, LA, Krakstad, C, Kjaer, SK, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lim, BK, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, McNeish, I, Menon, U, Milne, RL, Modugno, F, Moysich, KB, Ness, RB, Nevanlinna, H, Eilber, U, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Weber, RP, Paul, J, Pearce, CL, Pejovic, T, Pelttari, LM, Pike, MC, Poole, EM, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schernhammer, E, Schwaab, I, Shu, X-O, Shvetsov, YB, Siddiqui, N, Sieh, W, Song, H, Southey, MC, Spiewankiewicz, B, Sucheston, L, Teo, S-H, Terry, KL, Thompson, PJ, Thomsen, L, Tangen, IL, Tworoger, SS, van Altena, AM, Vierkant, RA, Vergote, I, Walsh, CS, Wang-Gohrke, S, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, LR, Wu, AH, Wu, X, Woo, Y-L, Yang, H, Zheng, W, Ziogas, A, Hasmad, HN, Berchuck, A, Iversen, ES, Schildkraut, JM, Ramus, SJ, Goode, EL, Monteiro, ANA, Gayther, SA, Narod, SA, Pharoah, PP, Sellers, TA, and Phelan, CM

Abstract

BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). CONCLUSION: These results, generated on a large cohort of women, revealed associatio

Published
2015

17. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC).

Author

Jim, HSL, Lin, H-Y, Tyrer, JP, Lawrenson, K, Dennis, J, Chornokur, G, Chen, Z, Chen, AY, Permuth-Wey, J, Aben, KK, Anton-Culver, H, Antonenkova, N, Bruinsma, F, Bandera, EV, Bean, YT, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bunker, CH, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, du Bois, A, Despierre, E, Sieh, W, Doherty, JA, Dörk, T, Dürst, M, Easton, DF, Eccles, DM, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goodman, MT, Gronwald, J, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, CK, Hogdall, E, Hosono, S, Iversen, ES, Jakubowska, A, Jensen, A, Ji, B-T, Karlan, BY, Kellar, M, Kiemeney, LA, Krakstad, C, Kjaer, SK, Kupryjanczyk, J, Vierkant, RA, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lim, BK, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, McNeish, I, Menon, U, Milne, RL, Modugno, F, Thomsen, L, Moysich, KB, Ness, RB, Nevanlinna, H, Eilber, U, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Palmieri Weber, R, Paul, J, Pearce, CL, Pejovic, T, Pelttari, LM, Pike, MC, Poole, EM, Schernhammer, E, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schwaab, I, Shu, X-O, Shvetsov, YB, Siddiqui, N, Song, H, Southey, MC, Spiewankiewicz, B, Sucheston-Campbell, L, Teo, S-H, Terry, KL, Thompson, PJ, Tangen, IL, Tworoger, SS, van Altena, AM, Vergote, I, Walsh, CS, Wang-Gohrke, S, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, LR, Wu, AH, Wu, X, Woo, Y-L, Yang, H, Zheng, W, Ziogas, A, Amankwah, E, Berchuck, A, Georgia Chenevix-Trench on behalf of the AOCS management group 95,96, Schildkraut, JM, Kelemen, LE, Ramus, SJ, Monteiro, ANA, Goode, EL, Narod, SA, Gayther, SA, Pharoah, PDP, Sellers, TA, Phelan, CM, Jim, HSL, Lin, H-Y, Tyrer, JP, Lawrenson, K, Dennis, J, Chornokur, G, Chen, Z, Chen, AY, Permuth-Wey, J, Aben, KK, Anton-Culver, H, Antonenkova, N, Bruinsma, F, Bandera, EV, Bean, YT, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bunker, CH, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, du Bois, A, Despierre, E, Sieh, W, Doherty, JA, Dörk, T, Dürst, M, Easton, DF, Eccles, DM, Edwards, RP, Ekici, AB, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goodman, MT, Gronwald, J, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, CK, Hogdall, E, Hosono, S, Iversen, ES, Jakubowska, A, Jensen, A, Ji, B-T, Karlan, BY, Kellar, M, Kiemeney, LA, Krakstad, C, Kjaer, SK, Kupryjanczyk, J, Vierkant, RA, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lim, BK, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, McNeish, I, Menon, U, Milne, RL, Modugno, F, Thomsen, L, Moysich, KB, Ness, RB, Nevanlinna, H, Eilber, U, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Palmieri Weber, R, Paul, J, Pearce, CL, Pejovic, T, Pelttari, LM, Pike, MC, Poole, EM, Schernhammer, E, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schwaab, I, Shu, X-O, Shvetsov, YB, Siddiqui, N, Song, H, Southey, MC, Spiewankiewicz, B, Sucheston-Campbell, L, Teo, S-H, Terry, KL, Thompson, PJ, Tangen, IL, Tworoger, SS, van Altena, AM, Vergote, I, Walsh, CS, Wang-Gohrke, S, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, LR, Wu, AH, Wu, X, Woo, Y-L, Yang, H, Zheng, W, Ziogas, A, Amankwah, E, Berchuck, A, Georgia Chenevix-Trench on behalf of the AOCS management group 95,96, Schildkraut, JM, Kelemen, LE, Ramus, SJ, Monteiro, ANA, Goode, EL, Narod, SA, Gayther, SA, Pharoah, PDP, Sellers, TA, and Phelan, CM

Abstract

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10-4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.

Published
2015

18. Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Author

Kuchenbaecker, KB, Ramus, SJ, Tyrer, J, Lee, A, Shen, HC, Beesley, J, Lawrenson, K, McGuffog, L, Healey, S, Lee, JM, Spindler, TJ, Lin, YG, Pejovic, T, Bean, Y, Li, Q, Coetzee, S, Hazelett, D, Miron, A, Southey, M, Terry, MB, Goldgar, DE, Buys, SS, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Neuhausen, SL, Ding, YC, Hansen, TVO, Jonson, L, Gerdes, A-M, Ejlertsen, B, Barrowdale, D, Dennis, J, Benitez, J, Osorio, A, Garcia, MJ, Komenaka, I, Weitzel, JN, Ganschow, P, Peterlongo, P, Bernard, L, Viel, A, Bonanni, B, Peissel, B, Manoukian, S, Radice, P, Papi, L, Ottini, L, Fostira, F, Konstantopoulou, I, Garber, J, Frost, D, Perkins, J, Platte, R, Ellis, S, Godwin, AK, Schmutzler, RK, Meindl, A, Engel, C, Sutter, C, Sinilnikova, OM, Damiola, F, Mazoyer, S, Stoppa-Lyonnet, D, Claes, K, De Leeneer, K, Kirk, J, Rodriguez, GC, Piedmonte, M, O'Malley, DM, de la Hoya, M, Caldes, T, Aittomaeki, K, Nevanlinna, H, Collee, JM, Rookus, MA, Oosterwijk, JC, Tihomirova, L, Tung, N, Hamann, U, Isaccs, C, Tischkowitz, M, Imyanitov, EN, Caligo, MA, Campbell, IG, Hogervorst, FBL, Olah, E, Diez, O, Blanco, I, Brunet, J, Lazaroso, C, Angel Pujana, M, Jakubowska, A, Gronwald, J, Lubinski, J, Sukiennicki, G, Barkardottir, RB, Plante, M, Simard, J, Soucy, P, Montagna, M, Tognazzo, S, Teixeira, MR, Pankratz, VS, Wang, X, Lindor, N, Szabo, CI, Kauff, N, Vijai, J, Aghajanian, CA, Pfeiler, G, Berger, A, Singer, CF, Tea, M-K, Phelan, CM, Greene, MH, Mai, PL, Rennert, G, Mulligan, AM, Tchatchou, S, Andrulis, IL, Glendon, G, Toland, AE, Jensen, UB, Kruse, TA, Thomassen, M, Bojesen, A, Zidan, J, Friedman, E, Laitman, Y, Soller, M, Liljegren, A, Arver, B, Einbeigi, Z, Stenmark-Askmalm, M, Olopade, OI, Nussbaum, RL, Rebbeck, TR, Nathanson, KL, Domchek, SM, Lu, KH, Karlan, BY, Walsh, C, Lester, J, Hein, A, Ekici, AB, Beckmann, MW, Fasching, PA, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I, Lambrechts, S, Dicks, E, Doherty, JA, Wicklund, KG, Rossing, MA, Rudolph, A, Chang-Claude, J, Wang-Gohrke, S, Eilber, U, Moysich, KB, Odunsi, K, Sucheston, L, Lele, S, Wilkens, LR, Goodman, MT, Thompson, PJ, Shvetsov, YB, Runnebaum, IB, Duerst, M, Hillemanns, P, Doerk, T, Antonenkova, N, Bogdanova, N, Leminen, A, Pelttari, LM, Butzow, R, Modugno, F, Kelley, JL, Edwards, RP, Ness, RB, du Bois, A, Heitz, F, Schwaab, I, Harter, P, Matsuo, K, Hosono, S, Orsulic, S, Jensen, A, Kjaer, SK, Hogdall, E, Hasmad, HN, Azmi, MAN, Teo, S-H, Woo, Y-L, Fridley, BL, Goode, EL, Cunningham, JM, Vierkant, RA, Bruinsma, F, Giles, GG, Liang, D, Hildebrandt, MAT, Wu, X, Levine, DA, Bisogna, M, Berchuck, A, Iversen, ES, Schildkraut, JM, Concannon, P, Weber, RP, Cramer, DW, Terry, KL, Poole, EM, Tworoger, SS, Bandera, EV, Orlow, I, Olson, SH, Krakstad, C, Salvesen, HB, Tangen, IL, Bjorge, L, van Altena, AM, Aben, KKH, Kiemeney, LA, Massuger, LFAG, Kellar, M, Brooks-Wilson, A, Kelemen, LE, Cook, LS, Le, ND, Cybulski, C, Yang, H, Lissowska, J, Brinton, LA, Wentzensen, N, Hogdall, C, Lundvall, L, Nedergaard, L, Baker, H, Song, H, Eccles, D, McNeish, I, Paul, J, Carty, K, Siddiqui, N, Glasspool, R, Whittemore, AS, Rothstein, JH, McGuire, V, Sieh, W, Ji, B-T, Zheng, W, Shu, X-O, Gao, Y-T, Rosen, B, Risch, HA, McLaughlin, JR, Narod, SA, Monteiro, AN, Chen, A, Lin, H-Y, Permuth-Wey, J, Sellers, TA, Tsai, Y-Y, Chen, Z, Ziogas, A, Anton-Culver, H, Gentry-Maharaj, A, Menon, U, Harrington, P, Lee, AW, Wu, AH, Pearce, CL, Coetzee, G, Pike, MC, Dansonka-Mieszkowska, A, Timorek, A, Rzepecka, IK, Kupryjanczyk, J, Freedman, M, Noushmehr, H, Easton, DF, Offit, K, Couch, FJ, Gayther, S, Pharoah, PP, Antoniou, AC, Chenevix-Trench, G, Kuchenbaecker, KB, Ramus, SJ, Tyrer, J, Lee, A, Shen, HC, Beesley, J, Lawrenson, K, McGuffog, L, Healey, S, Lee, JM, Spindler, TJ, Lin, YG, Pejovic, T, Bean, Y, Li, Q, Coetzee, S, Hazelett, D, Miron, A, Southey, M, Terry, MB, Goldgar, DE, Buys, SS, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Neuhausen, SL, Ding, YC, Hansen, TVO, Jonson, L, Gerdes, A-M, Ejlertsen, B, Barrowdale, D, Dennis, J, Benitez, J, Osorio, A, Garcia, MJ, Komenaka, I, Weitzel, JN, Ganschow, P, Peterlongo, P, Bernard, L, Viel, A, Bonanni, B, Peissel, B, Manoukian, S, Radice, P, Papi, L, Ottini, L, Fostira, F, Konstantopoulou, I, Garber, J, Frost, D, Perkins, J, Platte, R, Ellis, S, Godwin, AK, Schmutzler, RK, Meindl, A, Engel, C, Sutter, C, Sinilnikova, OM, Damiola, F, Mazoyer, S, Stoppa-Lyonnet, D, Claes, K, De Leeneer, K, Kirk, J, Rodriguez, GC, Piedmonte, M, O'Malley, DM, de la Hoya, M, Caldes, T, Aittomaeki, K, Nevanlinna, H, Collee, JM, Rookus, MA, Oosterwijk, JC, Tihomirova, L, Tung, N, Hamann, U, Isaccs, C, Tischkowitz, M, Imyanitov, EN, Caligo, MA, Campbell, IG, Hogervorst, FBL, Olah, E, Diez, O, Blanco, I, Brunet, J, Lazaroso, C, Angel Pujana, M, Jakubowska, A, Gronwald, J, Lubinski, J, Sukiennicki, G, Barkardottir, RB, Plante, M, Simard, J, Soucy, P, Montagna, M, Tognazzo, S, Teixeira, MR, Pankratz, VS, Wang, X, Lindor, N, Szabo, CI, Kauff, N, Vijai, J, Aghajanian, CA, Pfeiler, G, Berger, A, Singer, CF, Tea, M-K, Phelan, CM, Greene, MH, Mai, PL, Rennert, G, Mulligan, AM, Tchatchou, S, Andrulis, IL, Glendon, G, Toland, AE, Jensen, UB, Kruse, TA, Thomassen, M, Bojesen, A, Zidan, J, Friedman, E, Laitman, Y, Soller, M, Liljegren, A, Arver, B, Einbeigi, Z, Stenmark-Askmalm, M, Olopade, OI, Nussbaum, RL, Rebbeck, TR, Nathanson, KL, Domchek, SM, Lu, KH, Karlan, BY, Walsh, C, Lester, J, Hein, A, Ekici, AB, Beckmann, MW, Fasching, PA, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I, Lambrechts, S, Dicks, E, Doherty, JA, Wicklund, KG, Rossing, MA, Rudolph, A, Chang-Claude, J, Wang-Gohrke, S, Eilber, U, Moysich, KB, Odunsi, K, Sucheston, L, Lele, S, Wilkens, LR, Goodman, MT, Thompson, PJ, Shvetsov, YB, Runnebaum, IB, Duerst, M, Hillemanns, P, Doerk, T, Antonenkova, N, Bogdanova, N, Leminen, A, Pelttari, LM, Butzow, R, Modugno, F, Kelley, JL, Edwards, RP, Ness, RB, du Bois, A, Heitz, F, Schwaab, I, Harter, P, Matsuo, K, Hosono, S, Orsulic, S, Jensen, A, Kjaer, SK, Hogdall, E, Hasmad, HN, Azmi, MAN, Teo, S-H, Woo, Y-L, Fridley, BL, Goode, EL, Cunningham, JM, Vierkant, RA, Bruinsma, F, Giles, GG, Liang, D, Hildebrandt, MAT, Wu, X, Levine, DA, Bisogna, M, Berchuck, A, Iversen, ES, Schildkraut, JM, Concannon, P, Weber, RP, Cramer, DW, Terry, KL, Poole, EM, Tworoger, SS, Bandera, EV, Orlow, I, Olson, SH, Krakstad, C, Salvesen, HB, Tangen, IL, Bjorge, L, van Altena, AM, Aben, KKH, Kiemeney, LA, Massuger, LFAG, Kellar, M, Brooks-Wilson, A, Kelemen, LE, Cook, LS, Le, ND, Cybulski, C, Yang, H, Lissowska, J, Brinton, LA, Wentzensen, N, Hogdall, C, Lundvall, L, Nedergaard, L, Baker, H, Song, H, Eccles, D, McNeish, I, Paul, J, Carty, K, Siddiqui, N, Glasspool, R, Whittemore, AS, Rothstein, JH, McGuire, V, Sieh, W, Ji, B-T, Zheng, W, Shu, X-O, Gao, Y-T, Rosen, B, Risch, HA, McLaughlin, JR, Narod, SA, Monteiro, AN, Chen, A, Lin, H-Y, Permuth-Wey, J, Sellers, TA, Tsai, Y-Y, Chen, Z, Ziogas, A, Anton-Culver, H, Gentry-Maharaj, A, Menon, U, Harrington, P, Lee, AW, Wu, AH, Pearce, CL, Coetzee, G, Pike, MC, Dansonka-Mieszkowska, A, Timorek, A, Rzepecka, IK, Kupryjanczyk, J, Freedman, M, Noushmehr, H, Easton, DF, Offit, K, Couch, FJ, Gayther, S, Pharoah, PP, Antoniou, AC, and Chenevix-Trench, G

Abstract

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

Published
2015

19. Genome-wide significant risk associations for mucinous ovarian carcinoma

Author

Kelemen, LE, Lawrenson, K, Tyrer, J, Li, Q, Lee, JM, Seo, J-H, Phelan, CM, Beesley, J, Chen, X, Spindler, TJ, Aben, KKH, Anton-Culver, H, Antonenkova, N, Baker, H, Bandera, EV, Bean, Y, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bruinsma, F, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Chen, YA, Chen, Z, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, Dennis, J, Dicks, E, Doherty, JA, Doerk, T, du Bois, A, Duerst, M, Eccles, D, Easton, DT, Edwards, RP, Eilber, U, Ekici, AB, Engelholm, SA, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goode, EL, Goodman, MT, Grownwald, J, Harrington, P, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, E, Hogdall, C, Hosono, S, Iversen, ES, Jakubowska, A, Jensen, A, Ji, B-T, Karlan, BY, Kellar, M, Kelley, JL, Kiemeney, LA, Krakstad, C, Kjaer, SK, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, McNeish, I, Menon, U, Modugno, F, Moes-Sosnowska, J, Moysich, KB, Narod, SA, Nedergaard, L, Ness, RB, Nevanlinna, H, Adenan, NAM, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Weber, RP, Paul, J, Pearce, CL, Pejovic, T, Pelttari, LM, Permuth-Wey, J, Pike, MC, Poole, EM, Ramus, SJ, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schildkraut, JM, Schwaab, I, Shu, X-O, Shvetsov, YB, Siddiqui, N, Sieh, W, Song, H, Southey, MC, Sucheston, L, Tangen, IL, Teo, S-H, Terry, KL, Thompson, PJ, Tworoger, SS, van Altena, AM, Van Nieuwenhuysen, E, Vergote, I, Vierkant, RA, Wang-Gohrke, S, Walsh, C, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, LR, Sawicki, W, Woo, Y-L, Wu, X, Wu, AH, Yang, H, Zheng, W, Ziogas, A, Sellers, TA, Freedman, ML, Chenevix-Trench, G, Pharoah, PDP, Gayther, SA, Berchuck, A, Kelemen, LE, Lawrenson, K, Tyrer, J, Li, Q, Lee, JM, Seo, J-H, Phelan, CM, Beesley, J, Chen, X, Spindler, TJ, Aben, KKH, Anton-Culver, H, Antonenkova, N, Baker, H, Bandera, EV, Bean, Y, Beckmann, MW, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bruinsma, F, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Chen, YA, Chen, Z, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, Dennis, J, Dicks, E, Doherty, JA, Doerk, T, du Bois, A, Duerst, M, Eccles, D, Easton, DT, Edwards, RP, Eilber, U, Ekici, AB, Engelholm, SA, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goode, EL, Goodman, MT, Grownwald, J, Harrington, P, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, E, Hogdall, C, Hosono, S, Iversen, ES, Jakubowska, A, Jensen, A, Ji, B-T, Karlan, BY, Kellar, M, Kelley, JL, Kiemeney, LA, Krakstad, C, Kjaer, SK, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, McNeish, I, Menon, U, Modugno, F, Moes-Sosnowska, J, Moysich, KB, Narod, SA, Nedergaard, L, Ness, RB, Nevanlinna, H, Adenan, NAM, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Weber, RP, Paul, J, Pearce, CL, Pejovic, T, Pelttari, LM, Permuth-Wey, J, Pike, MC, Poole, EM, Ramus, SJ, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schildkraut, JM, Schwaab, I, Shu, X-O, Shvetsov, YB, Siddiqui, N, Sieh, W, Song, H, Southey, MC, Sucheston, L, Tangen, IL, Teo, S-H, Terry, KL, Thompson, PJ, Tworoger, SS, van Altena, AM, Van Nieuwenhuysen, E, Vergote, I, Vierkant, RA, Wang-Gohrke, S, Walsh, C, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, LR, Sawicki, W, Woo, Y-L, Wu, X, Wu, AH, Yang, H, Zheng, W, Ziogas, A, Sellers, TA, Freedman, ML, Chenevix-Trench, G, Pharoah, PDP, Gayther, SA, and Berchuck, A

Abstract

Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10(-8)), rs711830 at 2q31.1 (P = 7.5 × 10(-12)) and rs688187 at 19q13.2 (P = 6.8 × 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

Published
2015

20. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

Author

Lawrenson, K, Li, Q, Kar, S, Seo, J-H, Tyrer, J, Spindler, TJ, Lee, J, Chen, Y, Karst, A, Drapkin, R, Aben, KKH, Anton-Culver, H, Antonenkova, N, Baker, H, Bandera, EV, Bean, Y, Beckmann, MW, Berchuck, A, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bruinsma, F, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Chenevix-Trench, G, Chen, A, Chen, Z, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, Dennis, J, Dicks, E, Doherty, JA, Doerk, T, Du Bois, A, Duerst, M, Eccles, D, Easton, DT, Edwards, RP, Eilber, U, Ekici, AB, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goode, EL, Goodman, MT, Grownwald, J, Harrington, P, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, E, Hogdall, C, Hosono, S, Iversen, ES, Jakubowska, A, James, P, Jensen, A, Ji, B-T, Karlan, BY, Kjaer, SK, Kelemen, LE, Kellar, M, Kelley, JL, Kiemeney, LA, Krakstad, C, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, Nevanlinna, H, McNeish, I, Menon, U, Modugno, F, Moysich, KB, Narod, SA, Nedergaard, L, Ness, RB, Azmi, MAN, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Weber, RP, Pearce, CL, Pejovic, T, Pelttari, LM, Permuth-Wey, J, Phelan, CM, Pike, MC, Poole, EM, Ramus, SJ, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schildkraut, JM, Schwaab, I, Sellers, TA, Shu, X-O, Shvetsov, YB, Siddiqui, N, Sieh, W, Song, H, Southey, MC, Sucheston, L, Tangen, IL, Teo, S-H, Terry, KL, Thompson, PJ, Timorek, A, Tsai, Y-Y, Tworoger, SS, Van Altena, AM, Van Nieuwenhuysen, E, Vergote, I, Vierkant, RA, Wang-Gohrke, S, Walsh, C, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, LR, Woo, Y-L, Wu, X, Wu, AH, Yang, H, Zheng, W, Ziogas, A, Monteiro, A, Pharoah, PD, Gayther, SA, Freedman, ML, Grp, AOCS, Bowtell, D, Webb, PM, Defazio, A, Lawrenson, K, Li, Q, Kar, S, Seo, J-H, Tyrer, J, Spindler, TJ, Lee, J, Chen, Y, Karst, A, Drapkin, R, Aben, KKH, Anton-Culver, H, Antonenkova, N, Baker, H, Bandera, EV, Bean, Y, Beckmann, MW, Berchuck, A, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, LA, Brooks-Wilson, A, Bruinsma, F, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Chenevix-Trench, G, Chen, A, Chen, Z, Cook, LS, Cramer, DW, Cunningham, JM, Cybulski, C, Dansonka-Mieszkowska, A, Dennis, J, Dicks, E, Doherty, JA, Doerk, T, Du Bois, A, Duerst, M, Eccles, D, Easton, DT, Edwards, RP, Eilber, U, Ekici, AB, Fasching, PA, Fridley, BL, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goode, EL, Goodman, MT, Grownwald, J, Harrington, P, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, E, Hogdall, C, Hosono, S, Iversen, ES, Jakubowska, A, James, P, Jensen, A, Ji, B-T, Karlan, BY, Kjaer, SK, Kelemen, LE, Kellar, M, Kelley, JL, Kiemeney, LA, Krakstad, C, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, DA, Liang, D, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, Nevanlinna, H, McNeish, I, Menon, U, Modugno, F, Moysich, KB, Narod, SA, Nedergaard, L, Ness, RB, Azmi, MAN, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Weber, RP, Pearce, CL, Pejovic, T, Pelttari, LM, Permuth-Wey, J, Phelan, CM, Pike, MC, Poole, EM, Ramus, SJ, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schildkraut, JM, Schwaab, I, Sellers, TA, Shu, X-O, Shvetsov, YB, Siddiqui, N, Sieh, W, Song, H, Southey, MC, Sucheston, L, Tangen, IL, Teo, S-H, Terry, KL, Thompson, PJ, Timorek, A, Tsai, Y-Y, Tworoger, SS, Van Altena, AM, Van Nieuwenhuysen, E, Vergote, I, Vierkant, RA, Wang-Gohrke, S, Walsh, C, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, LR, Woo, Y-L, Wu, X, Wu, AH, Yang, H, Zheng, W, Ziogas, A, Monteiro, A, Pharoah, PD, Gayther, SA, Freedman, ML, Grp, AOCS, Bowtell, D, Webb, PM, and Defazio, A

Abstract

Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.

Published
2015

21. Haemorrhagic low-grade fibromyxoid sarcoma: MR findings in two young women

Author

Chung Yg, Won-Hee Jee, Sun Ki Kim, and Lee Aw

Subjects
Adult, Pathology, medicine.medical_specialty, Soft Tissue Neoplasm, Fibrosarcoma, Treatment outcome, Case Report, Hemorrhage, Soft Tissue Neoplasms, Thigh, Metastasis, Low-grade fibromyxoid sarcoma, Young Adult, medicine, Humans, Radiology, Nuclear Medicine and imaging, business.industry, General Medicine, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Treatment Outcome, Female, Sarcoma, business
Abstract

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue sarcoma characterised by a deceptively bland histological appearance and a paradoxically aggressive behaviour. LGFMS usually presents in young-to-middle-aged adults as a painless, slow-growing mass with the potential for local recurrence and metastasis despite low-grade histology. Several case reports have described variable MR findings of LGFMS without haemorrhage or necrosis. We report here on the MR findings in two young women with haemorrhagic LGFMS in the thigh.

Published
2011

22. Alloimmunization in Chinese with warm autoimmune haemolytic anaemia - incidence and characteristics

Author

Yu Ph, Lee Aw, So Cc, Kwan Am, and Kin Fai Ellick Wong

Subjects
Adult, Male, Population, Autoimmune Diseases, Asian People, Antibody Specificity, Isoantibodies, Humans, Medicine, Direct antiglobulin test, education, Aged, Autoantibodies, Retrospective Studies, Aged, 80 and over, education.field_of_study, Rh-Hr Blood-Group System, Red Cell, business.industry, Incidence (epidemiology), Temperature, Autoantibody, Transfusion Reaction, Retrospective cohort study, Hematology, Middle Aged, Antibodies, Anti-Idiotypic, Coombs Test, Blood Grouping and Crossmatching, Blood Group Incompatibility, Immunology, Hong Kong, Female, Immunization, Anemia, Hemolytic, Autoimmune, business
Abstract

We perform a retrospective study to determine the incidence and characteristics of alloimmunization in Chinese patients with warm autoimmune haemolytic anaemia. Among 67 patients studied, clinically significant alloantibodies were found in only eight patients, giving a rate of alloimmunization of 11.3%. The latter contrasts with the much higher rate reported in the Western population. This probably reflects the genetic homogeneity in Chinese with respect to the red cell phenotype. The alloimmunization rate, however, is still significant and therefore comprehensive pretransfusion testing is required for Chinese patients with warm autoantibodies so as to safeguard patient's safety.

Published
2000

24. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

Author

Shen, H, Fridley, BL, Song, H, Lawrenson, K, Cunningham, JM, Ramus, SJ, Cicek, MS, Tyrer, J, Stram, D, Larson, MC, Koebel, M, Ziogas, A, Zheng, W, Yang, HP, Wu, AH, Wozniak, EL, Woo, YL, Winterhoff, B, Wik, E, Whittemore, AS, Wentzensen, N, Weber, RP, Vitonis, AF, Vincent, D, Vierkant, RA, Vergote, I, Van Den Berg, D, Van Altena, AM, Tworoger, SS, Thompson, PJ, Tessier, DC, Terry, KL, Teo, S-H, Templeman, C, Stram, DO, Southey, MC, Sieh, W, Siddiqui, N, Shvetsov, YB, Shu, X-O, Shridhar, V, Wang-Gohrke, S, Severi, G, Schwaab, I, Salvesen, HB, Rzepecka, IK, Runnebaum, IB, Rossing, MA, Rodriguez-Rodriguez, L, Risch, HA, Renner, SP, Poole, EM, Pike, MC, Phelan, CM, Pelttari, LM, Pejovic, T, Paul, J, Orlow, I, Omar, SZ, Olson, SH, Odunsi, K, Nickels, S, Nevanlinna, H, Ness, RB, Narod, SA, Nakanishi, T, Moysich, KB, Monteiro, ANA, Moes-Sosnowska, J, Modugno, F, Menon, U, McLaughlin, JR, McGuire, V, Matsuo, K, Adenan, NAM, Massuger, LFAG, Lurie, G, Lundvall, L, Lubinski, J, Lissowska, J, Levine, DA, Leminen, A, Lee, AW, Le, ND, Lambrechts, S, Lambrechts, D, Kupryjanczyk, J, Krakstad, C, Konecny, GE, Kjaer, SK, Kiemeney, LA, Kelemen, LE, Keeney, GL, Karlan, BY, Karevan, R, Kalli, KR, Kajiyama, H, Ji, B-T, Jensen, A, Jakubowska, A, Iversen, E, Hosono, S, Hogdall, CK, Hogdall, E, Hoatlin, M, Hillemanns, P, Heitz, F, Hein, R, Harter, P, Halle, MK, Hall, P, Gronwald, J, Gore, M, Goodman, MT, Giles, GG, Gentry-Maharaj, A, Garcia-Closas, M, Flanagan, JM, Fasching, PA, Ekici, AB, Edwards, R, Eccles, D, Easton, DF, Duerst, M, du Bois, A, Doerk, T, Doherty, JA, Despierre, E, Dansonka-Mieszkowska, A, Cybulski, C, Cramer, DW, Cook, LS, Chen, X, Charbonneau, B, Chang-Claude, J, Campbell, I, Butzow, R, Bunker, CH, Brueggmann, D, Brown, R, Brooks-Wilson, A, Brinton, LA, Bogdanova, N, Block, MS, Benjamin, E, Beesley, J, Beckmann, MW, Bandera, EV, Baglietto, L, Bacot, F, Armasu, SM, Antonenkova, N, Anton-Culver, H, Aben, KK, Liang, D, Wu, X, Lu, K, Hildebrandt, MAT, Schildkraut, JM, Sellers, TA, Huntsman, D, Berchuck, A, Chenevix-Trench, G, Gayther, SA, Pharoah, PDP, Laird, PW, Goode, EL, Pearce, CL, Shen, H, Fridley, BL, Song, H, Lawrenson, K, Cunningham, JM, Ramus, SJ, Cicek, MS, Tyrer, J, Stram, D, Larson, MC, Koebel, M, Ziogas, A, Zheng, W, Yang, HP, Wu, AH, Wozniak, EL, Woo, YL, Winterhoff, B, Wik, E, Whittemore, AS, Wentzensen, N, Weber, RP, Vitonis, AF, Vincent, D, Vierkant, RA, Vergote, I, Van Den Berg, D, Van Altena, AM, Tworoger, SS, Thompson, PJ, Tessier, DC, Terry, KL, Teo, S-H, Templeman, C, Stram, DO, Southey, MC, Sieh, W, Siddiqui, N, Shvetsov, YB, Shu, X-O, Shridhar, V, Wang-Gohrke, S, Severi, G, Schwaab, I, Salvesen, HB, Rzepecka, IK, Runnebaum, IB, Rossing, MA, Rodriguez-Rodriguez, L, Risch, HA, Renner, SP, Poole, EM, Pike, MC, Phelan, CM, Pelttari, LM, Pejovic, T, Paul, J, Orlow, I, Omar, SZ, Olson, SH, Odunsi, K, Nickels, S, Nevanlinna, H, Ness, RB, Narod, SA, Nakanishi, T, Moysich, KB, Monteiro, ANA, Moes-Sosnowska, J, Modugno, F, Menon, U, McLaughlin, JR, McGuire, V, Matsuo, K, Adenan, NAM, Massuger, LFAG, Lurie, G, Lundvall, L, Lubinski, J, Lissowska, J, Levine, DA, Leminen, A, Lee, AW, Le, ND, Lambrechts, S, Lambrechts, D, Kupryjanczyk, J, Krakstad, C, Konecny, GE, Kjaer, SK, Kiemeney, LA, Kelemen, LE, Keeney, GL, Karlan, BY, Karevan, R, Kalli, KR, Kajiyama, H, Ji, B-T, Jensen, A, Jakubowska, A, Iversen, E, Hosono, S, Hogdall, CK, Hogdall, E, Hoatlin, M, Hillemanns, P, Heitz, F, Hein, R, Harter, P, Halle, MK, Hall, P, Gronwald, J, Gore, M, Goodman, MT, Giles, GG, Gentry-Maharaj, A, Garcia-Closas, M, Flanagan, JM, Fasching, PA, Ekici, AB, Edwards, R, Eccles, D, Easton, DF, Duerst, M, du Bois, A, Doerk, T, Doherty, JA, Despierre, E, Dansonka-Mieszkowska, A, Cybulski, C, Cramer, DW, Cook, LS, Chen, X, Charbonneau, B, Chang-Claude, J, Campbell, I, Butzow, R, Bunker, CH, Brueggmann, D, Brown, R, Brooks-Wilson, A, Brinton, LA, Bogdanova, N, Block, MS, Benjamin, E, Beesley, J, Beckmann, MW, Bandera, EV, Baglietto, L, Bacot, F, Armasu, SM, Antonenkova, N, Anton-Culver, H, Aben, KK, Liang, D, Wu, X, Lu, K, Hildebrandt, MAT, Schildkraut, JM, Sellers, TA, Huntsman, D, Berchuck, A, Chenevix-Trench, G, Gayther, SA, Pharoah, PDP, Laird, PW, Goode, EL, and Pearce, CL

Abstract

HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.

Published
2013

27. Imaging features of invasive lobular carcinoma: comparison with invasive ductal carcinoma.

Author

Kim SH, Cha ES, Park CS, Kang BJ, Whang IY, Lee AW, Song BJ, Park J, Kim, Sung Hun, Cha, Eun Suk, Park, Chang Suk, Kang, Bong Joo, Whang, In Yong, Lee, A Won, Song, Byung Joo, and Park, Jeongmi

Abstract

Purpose: The aim of this study was to evaluate the imaging findings of invasive lobular carcinoma (ILC) compared to those of invasive ductal carcinoma (IDC).Materials and Methods: The study included ILCs (n = 27) and IDCs (n = 85). Imaging findings were retrospectively evaluated, according to the BI-RADS lexicon. We compared the imaging findings, multiplicity, and magnetic resonance imaging (MRI) detection accuracy of ILC with those of IDC.Results: At mammography, normal findings and mass lesions were more frequent with ILCs (14.8% and 59.2%, respectively) than with IDCs (1.2% and 44.7%, respectively) (P = 0.009). With ultrasonography (US), posterior acoustic shadowing was more frequently seen in ILCs (59.2%) than in IDCs (15.8%) (P < 0.001). With MRI, both ILCs and IDCs most commonly appeared as a heterogeneously enhancing, irregular mass with a spiculated border. Multifocality was more frequently associated with ILCs (40.7%) than with IDCs (14.1% 1% 0.002). However, multicentricity and bilaterality were not different between the two groups. The sensitivity and specificity of MRI for the detection of multiplicity were 91.6% and 73.3%, respectively, for ILCs and 83.3% and 80.3%, respectively, for IDCs.Conclusion: Normal findings, mass lesions on mammography, and posterior acoustic shadowing on US were more frequently associated with ILCs than with IDCs. Multifocality was more prevalent with ILCs than with IDCs. [ABSTRACT FROM AUTHOR]

Published
2011
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28. Long-term durability of immune responses after hepatitis A vaccination among HIV-infected adults.

Author

Crum-Cianflone NF, Wilkins K, Lee AW, Grosso A, Landrum ML, Weintrob A, Ganesan A, Maguire J, Klopfer S, Brandt C, Bradley WP, Wallace MR, Agan BK, Infectious Disease Clinical Research Program HIV Working Group, Crum-Cianflone, Nancy F, Wilkins, Kenneth, Lee, Andrew W, Grosso, Anthony, Landrum, Michael L, and Weintrob, Amy

Abstract

Background: Vaccination provides long-term immunity to hepatitis A virus (HAV) among the general population, but there are no such data regarding vaccine durability among human immunodeficiency virus (HIV)-infected adults.Methods: We retrospectively studied HIV-infected adults who had received 2 doses of HAV vaccine. We analyzed blood specimens taken at 1 year, 3 years, and, when available, 6-10 years postvaccination. HAV immunoglobulin G (IgG) values of ≥10 mIU/mL were considered seropositive.Results: We evaluated specimens from 130 HIV-infected adults with a median age of 35 years and a median CD4 cell count of 461 cells/mm(3) at or before time of vaccination. Of these, 49% had an HIV RNA load <1000 copies/mL. Initial vaccine responses were achieved in 89% of HIV-infected adults (95% confidence interval [CI], 83%-94%), compared with 100% (95% CI, 99%-100%) of historical HIV-uninfected adults. Among initial HIV-infected responders with available specimens, 90% (104 of 116; 95% CI, 83%-95%) remained seropositive at 3 years and 85% (63 of 74; 95% CI, 75%-92%) at 6-10 years. Geometric mean concentrations (GMCs) among HIV-infected adults were 154, 111, and 64 mIU/mL at 1, 3, and 6-10 years, respectively, compared with 1734, 687, and 684 mIU/mL among HIV-uninfected persons. Higher GMCs over time among HIV-infected adults were associated with lower log(10) HIV RNA levels (β = -.12, P = .04).Conclusions: Most adults with well-controlled HIV infections had durable seropositive responses up to 6-10 years after HAV vaccination. Suppressed HIV RNA levels are associated with durable HAV responses. [ABSTRACT FROM AUTHOR]

Published
2011
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31. Grand rounds. Vision-related quality of life in patients with complete homonymous hemianopia post stroke.

Author

Chen CS, Lee AW, Clarke G, Hayes A, George S, Vincent R, Thompson A, Centrella L, Johnson K, Daly A, and Crotty M

Abstract

Purpose: The aim is to determine the characteristics of vision-specific quality of life restriction using the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and Veterans Affairs Low Vision Visual Function Questionnaire (VA LV VFQ-48) in patients with complete homonymous hemianopia (HH) post stroke.Method: Prospective cohort study of patients with complete HH compared to age- and gender-matched subjects with normal visual fields.Results: In the NEI VFQ-25, scores on five subscales were significantly reduced after multiple logistic regression accounting for vision and comorbidities. The five subscales are vision-specific social functioning, vision-specific mental health, vision-specific dependency, driving, and peripheral vision. In the VA LV VFQ-48 postregression analysis, mobility is the only domain that is significantly affected in the people with HH.Conclusion: Identification of the significant areas of visual difficulties and their effects on quality of life is important as it can help better address the patients' rehabilitation needs. The current study identifies the need for orientation and mobility training as well as independent living rehabilitation in patients with HH to help address the difficulties in their vision-specific quality of life and maximize their residual vision. [ABSTRACT FROM AUTHOR]

Published
2009
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35. PEG adsorption of autoantibodies and detection of alloantibodies in warm autoimmune hemolytic anemia.

Author

Cheng C, Wong ML, Lee AW, Cheng, C K, Wong, M L, and Lee, A W

Abstract

Background: The purpose of this study was to evaluate the effectiveness of PEG in the adsorption of autoantibodies and the detection of alloantibodies in patients with warm autoimmune hemolytic anemia (WAIHA).Study Design and Methods: The study was divided into three parts. First, the effectiveness of antibody removal by a conventional adsorption procedure and that by the PEG adsorption method were compared by using commercial antisera adsorbed with antigen-positive RBCs. Second, patients' sera with known weak alloanti-E were used to test against screening cells after allogeneic adsorption to show nonspecific coating of antibodies and the dilution effect on the PEG adsorption procedure. Third, conventional and PEG one-cell sample allogeneic adsorptions of WAIHA patients' sera with and without alloantibodies were performed and compared.Results: In the first part, seven of the eight polyclonal antisera gave a lower titer and score when tested against antigen-positive RBCs in the indirect antiglobulin test; this indicated that PEG is more efficient in removing antibodies. In the second part, similar reaction patterns were observed in antibody screening tests on unadsorbed sera and on sera after the first, second, and third adsorptions, which indicated that there was no alloantibody loss, nonspecific antibody coating, or dilution effect when PEG was added in the allogeneic adsorption procedures. In the third part, a 40-percent increase in efficiency in reducing the number of adsorptions and an 85-percent decrease in completion time of the adsorption procedures were obtained when PEG was used for adsorbing sera from 16 patients with WAIHA. Both conventional and PEG procedures were capable of removing autoantibodies to identify the specificities of alloantibodies.Conclusion: The PEG adsorption method is an effective, sensitive, and efficient method of enhancing auto- antibody adsorption and alloantibody detection. It can reduce the processing time and minimize the delay of urgent transfusions to patients with WAIHA and can indirectly enhance cost-effectiveness and decrease the labor-intensive testing required by these cases. [ABSTRACT FROM AUTHOR]

Published
2001
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37. Fluid Chemistry, Structural Setting, and Emplacement History of the Rosario Cu-Mo Porphyry and Cu-Ag-Au Epithermal Veins, Collahuasi District, Northern Chile

Author

Masterman, GJ, Cooke, DR, Berry, RF, Walshe, JL, Lee, AW, Clark, AH, Masterman, GJ, Cooke, DR, Berry, RF, Walshe, JL, Lee, AW, and Clark, AH

Abstract

The Rosario Cu-Mo-Ag deposit is located in the Collahuasi district of northern Chile. It comprises high-grade Cu-Ag-(Au) epithermal veins, superimposed on the core of a porphyry Cu-Mo orebody. Rosario has mining reserves of 1,094 million metric tons (Mt) at 1.03 percent copper. An additional 1,022 Mt at 0.93 percent copper occurs in the district at the nearby Ujina and Quebrada Blanca porphyry deposits. The Rosario reserve contains over 95 percent hypogene ore, whereas supergene-sulfide ores dominate at Ujina and Quebrada Blanca. Mineralized veins are hosted within Lower Permian volcanic and sedimentary rocks, Lower Triassic granodiorite and late Eocene porphyritic quartz-monzonite. The Rosario fault system, a series of moderate southwest- dipping faults, has localized high-grade Cu-Ag-(Au) veins. At Cerro La Grande, similar high-grade Cu- Ag-(Au) veins are hosted in north-northeast-trending, sinistral wrench faults. Normal movement in the Rosario fault system is interpreted to have been synchronous with sinistral strike-slip deformation at La Grande. Hydrothermal alteration at Rosario is characterized by a K-feldspar core, focused in the Rosario Porphyry that grades out to a secondary biotite-albite-magnetite assemblage. Paragenetic relationships indicate that magnetite was the earliest formed alteration product but has been replaced by biotite-albite. Vein crosscutting relationships indicate that K-feldspar formed during and after biotite-albite alteration. Chalcopyrite and bornite were deposited in quartz veins associated with both K-feldspar and biotite-albite assemblages. The early hydrothermal fluid was a hypersaline brine (40-45 wt % NaCl) that coexisted with vapor between 400 degrees and >600 degrees C. Weakly mineralized illite-chlorite (intermediate argillic) alteration of the early K and Na silicate assemblages was caused by moderate temperature (250 degrees-350 degrees C), moderate-salinity brines (10-15 wt % NaCl). Molybdenite was precipitated in quartz

38. Fluid Chemistry, Structural Setting, and Emplacement History of the Rosario Cu-Mo Porphyry and Cu-Ag-Au Epithermal Veins, Collahuasi District, Northern Chile

Author

Masterman, GJ, Cooke, DR, Berry, RF, Walshe, JL, Lee, AW, Clark, AH, Masterman, GJ, Cooke, DR, Berry, RF, Walshe, JL, Lee, AW, and Clark, AH

Abstract

The Rosario Cu-Mo-Ag deposit is located in the Collahuasi district of northern Chile. It comprises high-grade Cu-Ag-(Au) epithermal veins, superimposed on the core of a porphyry Cu-Mo orebody. Rosario has mining reserves of 1,094 million metric tons (Mt) at 1.03 percent copper. An additional 1,022 Mt at 0.93 percent copper occurs in the district at the nearby Ujina and Quebrada Blanca porphyry deposits. The Rosario reserve contains over 95 percent hypogene ore, whereas supergene-sulfide ores dominate at Ujina and Quebrada Blanca. Mineralized veins are hosted within Lower Permian volcanic and sedimentary rocks, Lower Triassic granodiorite and late Eocene porphyritic quartz-monzonite. The Rosario fault system, a series of moderate southwest- dipping faults, has localized high-grade Cu-Ag-(Au) veins. At Cerro La Grande, similar high-grade Cu- Ag-(Au) veins are hosted in north-northeast-trending, sinistral wrench faults. Normal movement in the Rosario fault system is interpreted to have been synchronous with sinistral strike-slip deformation at La Grande. Hydrothermal alteration at Rosario is characterized by a K-feldspar core, focused in the Rosario Porphyry that grades out to a secondary biotite-albite-magnetite assemblage. Paragenetic relationships indicate that magnetite was the earliest formed alteration product but has been replaced by biotite-albite. Vein crosscutting relationships indicate that K-feldspar formed during and after biotite-albite alteration. Chalcopyrite and bornite were deposited in quartz veins associated with both K-feldspar and biotite-albite assemblages. The early hydrothermal fluid was a hypersaline brine (40-45 wt % NaCl) that coexisted with vapor between 400 degrees and >600 degrees C. Weakly mineralized illite-chlorite (intermediate argillic) alteration of the early K and Na silicate assemblages was caused by moderate temperature (250 degrees-350 degrees C), moderate-salinity brines (10-15 wt % NaCl). Molybdenite was precipitated in quartz

41. A phase II study of pemetrexed combined with cisplatin in patients with recurrent or metastatic nanopharyngeal carcinoma.

Author

Yau TK, Shum T, Lee AW, Yeung MW, Ng WT, and Chan L

Abstract

Pemetrexed is a novel chemotherapy agent with good efficacy and toxicity profiles. This phase II study aimed at evaluating its use in combination with cisplatin for recurrent or metastatic nasopharyngeal carcinoma (NPC). All participating patients had metastatic or recurrent NPC with prior treatment by platinum-based chemotherapy. The study regimen comprised of pemetrexed 500mg/m(2) and cisplatin 75mg/m(2), repeated 3-weekly for 4 cycles. Efficacy evaluation was based on both radiological and biochemical responses. Patients with no progressive disease and good tolerance were given another 2-4 cycles. Fifteen patients were treated for a total of 4-8 cycles (median, 6 cycles); 9 had distant metastases and 6 had loco-regional recurrences only. Reduction of DNA copies of EB virus by 50% was observed in 93% accessible patients, with 21% of them being biochemical complete response (CR). Radiologically, 1 (7%) patient achieved CR, 2 (13%) achieved partial response and 8 (53%) had stable diseases. The median time to progression was 30weeks. Treatment was well tolerated with only 1 (7%) patient developing grade 4 toxicity (of anemia). The most common grade 3 toxicities were neutropenia (27%) and anemia (20%). The baseline mean total QOL scores (as measured with FACT-H&N version 4) was 100.4 and showed no significant change after the fourth cycle (95.6, p=0.20) and sixth cycle (91.9, p=0.15). Pemetrexed in combination with cisplatin is a well tolerated regimen with encouraging efficacy for metastatic and recurrent NPC. Further evaluation of its role in the management of NPC is warranted. [ABSTRACT FROM AUTHOR]

Published
2012

44. Trends and patterns of breast conservation treatment in Hong Kong: 1994-2007.

Author

Yau TK, Soong IS, Sze H, Choi CW, Yeung MW, Ng WT, Lee AW, Yau, Tsz-Kok, Soong, Inda S, Sze, Henry, Choi, Cheuk-Wai, Yeung, Mei-Wan, Ng, Wai-Tong, and Lee, Anne W M

Abstract

Purpose: Breast conservation treatment (BCT) was quite unpopular in Hong Kong until the early 1990s, but the trends and patterns of BCT use in the past 14 years have not been studied since. The purpose of this study was to identify the latest trends and patterns. Methods and Materials: All consecutive cases of female breast cancer referred to a community oncology center in Hong Kong between 1994 and 2007 were retrospectively reviewed. Of the 2,375 women with T1-2 invasive breast cancer who underwent surgery, 1,137 (48%) had T1 (2 cm-Results: Of the total patient cohort, 2,153 (91%) patients presented with palpable breast masses and only 104 (4%) with mammographically detected cancers. Overall, 721 (30%) and 1,654 (70%) patients underwent BCT and mastectomy, respectively. There was no significant increase in the BCT rates (31%, SD 5%; p = 0.804) or mammographic detection rates (5%, SD 1%; p = 0.125) in Hong Kong between 1994 and 2007. In multivariate analyses, age Conclusions: Our results indicate a satisfactory acceptance of BCT by patients who are young and have small tumors, node-negative disease, or surgery in private hospitals. However, the continuing unpopularity of breast screening is likely a major factor limiting the broad use of BCT. [ABSTRACT FROM AUTHOR]

Published
2009
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45. Disparities in ovarian cancer survival among ethnic Asian American populations, 2006-2020.

Author

Lee AW, Poynor V, and Siddiqui S

Abstract

Background: Asian Americans have the highest ovarian cancer survival across the major racial groups although it is unclear whether this survival advantage is observed when each Asian ethnic subgroup is examined separately. Disaggregated survival analyses of this heterogeneous population is needed to ensure ethnic-specific disparities are not overlooked., Methods: Data on ovarian cancer cases diagnosed from 2006 through 2020 from the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed. Age-standardized five-year cause-specific survival was calculated for Non-Hispanic Whites and seven Asian ethnic subgroups in the U.S. (Asian Indian/Pakistani, Chinese, Filipino, Hawaiian/Pacific Islander, Japanese, Korean, Vietnamese) by stage and histotype. Multivariable Cox regression analyses using a weighted approach were conducted to calculate average hazard ratios (AHRs) and 95 % confidence intervals (CIs) to quantify the risk of ovarian cancer death comparing each Asian ethnic subgroup to Non-Hispanic Whites., Results: Hawaiian/Pacific Islanders were the only Asian subgroup to show lower five-year cause-specific survival than Non-Hispanic Whites (44.99 % versus 47.90 %, respectively); Asian Indian/Pakistanis showed the highest survival (56.12 %). After adjusting for sociodemographic, tumor, and treatment characteristics, Asian Indian/Pakistani ovarian cancer patients were 17 % less likely to die from their disease whereas Hawaiian/Pacific Islander patients were 28 % more likely to die when compared to Non-Hispanic Whites (AHR = 0.83, 95 % CI 0.75-0.92 and AHR = 1.28, 95 % CI 1.07-1.53, respectively)., Conclusions: There are clear ethnic-specific survival disparities among Asian American ovarian cancer patients that are missed when the population is examined as a single group, further highlighting the need for data disaggregation in future ovarian cancer research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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46. Pre-diagnosis tea and coffee consumption and survival after a diagnosis of ovarian cancer: results from the Ovarian Cancer Association Consortium.

Author

Nagle CM, Ibiebele TI, Bandera EV, Cramer D, Doherty JA, Giles GG, Goodman MT, Hanley GE, Harris HR, Jensen A, Kjaer SK, Lee AW, Milne RL, Qin B, Richardson J, Sasamoto N, Sieh W, Terry KL, Titus L, Trabert B, Wentzensen N, Wu AH, Berchuck A, Pike M, Pearce CL, and Webb PM

Subjects
Humans, Female, Middle Aged, Aged, Proportional Hazards Models, Adult, Caffeine administration & dosage, Ovarian Neoplasms mortality, Ovarian Neoplasms diagnosis, Tea, Coffee
Abstract

Background: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain., Methods: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI)., Results: Compared with women who did not drink any green tea, consumption of one or more cups/day was associated with better overall survival (aHR = 0.84, 95% CI 0.71-1.00, p-trend = 0.04). A similar association was seen for ovarian cancer-specific survival in five studies with this information (aHR = 0.81, 0.66-0.99, p-trend = 0.045). There was no consistent variation between subgroups defined by clinical or lifestyle characteristics and adjustment for other aspects of lifestyle did not appreciably alter the estimates. We found no evidence of an association between coffee, black or herbal tea, or caffeine intake and survival., Conclusion: The observed association with green tea consumption before diagnosis raises the possibility that consumption after diagnosis might improve patient outcomes., (© 2024. The Author(s).)

Published
2024
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47. Conservative management of spinal pathology with autologous conditioned serum: A systematic review of the literature.

Author

Rajkovic CJ, Merckling ML, Lee AW, Subah G, Malhotra A, Thomas ZD, Zeller SL, Wainwright JV, and Kinon MD

Abstract

Background: Chronic inflammatory pain is associated with increased expression of interleukin (IL)-1, an inflammatory cytokine, and activity on its receptor (IL-1R). In response, the body produces IL-1R antagonist (IL-1Ra) to reduce this signaling. Autologous conditioned serum (ACS) is the only biologic therapy for spinal pathologies that enhances the action of endogenous IL-1Ra reserves to improve symptoms. This systematic review investigates the effectiveness of ACS in treating pain and disability caused by spinal pathologies., Aim: To evaluate the use of ACS as a conservative management option for spinal pathology., Methods: A systematic review of PubMed/Medline was performed to identify studies investigating administration of ACS for treatment of any spinal pathology., Results: Six articles were included, comprising 684 patients treated with epidural ( n = 133) or transforaminal ( n = 551) ACS injections. Patients had an average age of 54.0 years with slight female predominance (53.2%). The lumbar spine was most commonly treated, with 567 patients (82.9%) receiving injections for lumbar radiculopathy ( n = 67), degenerative disc disease (DDD) ( n = 372), or spinal stenosis ( n = 128); cervical injections were performed in 109 patients (15.9%). Mean (SD) follow-up was 21.7 (4.8) weeks from first ACS injection. All studies investigating mechanical lumbar and lumbar or cervical radicular pain reported significant pain reduction at final follow-up compared to baseline. ACS achieved comparable or superior results to lumbar epidural steroid injections. Adverse events were reported in 21 patients (3.1%), with no serious adverse events., Conclusion: ACS injection is a safe and effective intervention for pain reduction in many spinal pathologies, including cervical and lumbar radiculopathies., Competing Interests: Conflict-of-interest statement: Dr. Merritt Kinon reports stock and honorarium with Globus Medical, Inc and is a consultant for Sanara MedTech. The remaining authors have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Published
2024
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48. Listening to the Voice of the Patient in RSV Research.

Author

Lee AW, Thomas R, Chung B, and Bont LJ

Abstract

Patient and public involvement in research refers to patients or caregivers with disease experience contributing to the design, conduct or dissemination of results from research. Patient and public involvement has given rise to new fields in healthcare-oriented research and has the potential to transform infectious diseases through interventional trials. Our recommendations and best practices from years of organizing respiratory syncytial virus parent networks are provided., Competing Interests: A.W.L. has previously worked in the pharmaceutical industry, but was not employed in industry while the manuscript was authored and submitted for publication. B.C. is an employee of a for-profit company, Chorus Innovations, Inc. Louis Bont has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. Other authors have no conflicts of interest to disclose, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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49. Comprehensive identification of pathogenic microbes and antimicrobial resistance genes in food products using nanopore sequencing-based metagenomics.

Author

Lee AW, Ng IC, Wong EY, Wong IT, Sze RP, Chan KY, So TY, Zhang Z, Ka-Yee Fung S, Choi-Ying Wong S, Tam WY, Lao HY, Lee LK, Leung JS, Chan CT, Ng TT, Zhang J, Chow FW, Leung PH, and Siu GK

Subjects
Food Microbiology, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial genetics, Bacteria genetics, Metagenomics, Nanopore Sequencing, Anti-Infective Agents
Abstract

Foodborne pathogens, particularly antimicrobial-resistant (AMR) bacteria, remain a significant threat to global health. Given the limitations of conventional culture-based approaches, which are limited in scope and time-consuming, metagenomic sequencing of food products emerges as a promising solution. This method provides a fast and comprehensive way to detect the presence of pathogenic microbes and antimicrobial resistance genes (ARGs). Notably, nanopore long-read sequencing provides more accurate bacterial taxonomic classification in comparison to short-read sequencing. Here, we revealed the impact of food types and attributes (origin, retail place, and food processing methods) on microbial communities and the AMR profile using nanopore metagenomic sequencing. We analyzed a total of 260 food products, including raw meat, sashimi, and ready-to-eat (RTE) vegetables. Clostridium botulinum, Acinetobacter baumannii, and Vibrio parahaemolyticus were identified as the top three foodborne pathogens in raw meat and sashimi. Importantly, even with low pathogen abundance, higher percentages of samples containing carbapenem and cephalosporin resistance genes were identified in chicken and RTE vegetables, respectively. In parallel, our results demonstrated that fresh, peeled, and minced foods exhibited higher levels of pathogenic bacteria. In conclusion, this comprehensive study offers invaluable data that can contribute to food safety assessments and serve as a basis for quality indicators., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Ltd.)

Published
2024
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50. Transmission Patterns of Co-Circulation of Omicron Sub-Lineages in Hong Kong SAR, China, a City with Rigorous Social Distancing Measures, in 2022.

Author

Chow N, Long T, Lee LK, Wong IT, Lee AW, Tam WY, Wong HF, Leung JS, Chow FW, Luk KS, Ho AY, Lam JY, Yau MC, Que TL, Yip KT, Chow VC, Wong RC, Mok BW, Chen HL, and Siu GK

Subjects
Humans, Hong Kong epidemiology, Physical Distancing, Male, Female, Adult, Middle Aged, Adolescent, Child, Aged, Young Adult, COVID-19 epidemiology, COVID-19 transmission, COVID-19 virology, COVID-19 prevention & control, SARS-CoV-2 genetics, SARS-CoV-2 classification, Quarantine, Phylogeny, Genome, Viral
Abstract

Objective: This study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time., Methods: In 2022, a total of 4684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes was determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements., Results: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5, 47) = 18.233, p < 0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5, 47) = 2.037, p = 0.091)., Conclusion: This study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants.

Published
2024
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