Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Ferreiro-Iglesias, Aida; Lesseur, Corina; McKay, James; Hung, Rayjean J.; Han, Younghun; Zong, Xuchen; Christiani, David C.; Johansson, Mattias; Xiao, Xiangjun; Li, Yafang; Qian, David C.; Ji, Xuemei; Liu, Geoffrey; Caporaso, Neil E.; Scélo, Ghislaine; Заридзе, Давид; Mukeriya, Anush; Kontić, Milica; Ognjanovic, Simona; Lissowska, Jolanta; Szołkowska, Małgorzata; Świątkowska, Beata; Janout, Vladimí­r; Holcátová, Ivana; Bolca, Ciprian; Savić, Milan; Ognjanovic, Miodrag; Bojesen, Stig E.; Wu, Xifeng; Albanes, Demetrios; Aldrich, Melinda C.; Tardón, Adonina; Fernández-Somoano, Ana; Fernández‐Tardón, Guillermo; Marchand, Loı̈c Le; Rennert, Gad; Chen, Chu; Doherty, Jennifer A.; Goodman, Gary E.; Bickeböller, Heike; Wichmann, H‐Erich; Risch, Angela; Rosenberger, Albert; Shen, Hongbing; Dai, Juncheng; Field, John K.; Davies, Michael; Woll, Penella J.; Teare, M. Dawn; Kiemeney, Lambertus A.; Heijden, Erik H F M van der; Yuan, Jian‐Min; Hong, Yun-Chul; Haugen, Aage; Zienolddiny, Shanbeh; Lam, Stephen; Tsao, Ming‐Sound; Johansson, Mikael; Grankvist, Kjell; Schabath, Matthew B.; Andrew, Angeline S.; Duell, Eric J.; Melander, Olle; Brunnström, Hans; Lazarus, Philip; Arnold, Susanne M.; Slone, Stacey; Byun, Jinyoung; Kamal, Ahsan; Zhu, Dakai; Landi, Maria Teresa; Amos, Christopher I.; Brennan, Paul

doi:10.1038/s41467-018-05890-2

Cited by 47 publications

(38 citation statements)

References 43 publications

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“…The HLA region is critical for innate and adaptive immune response and has a complex relationship with cancer risk. Heterogeneous associations with HLA haplotypes have been reported for different subtypes of NHL 44 and lung cancer 45 , suggesting that relevant risk variants are likely to differ within, as well as between, cancers. Studies have further demonstrated that somatic mutation profiles are associated with HLA class I (ref.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts

et al. 2020

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Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of crosscancer susceptibility.

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Section: Discussionmentioning

confidence: 99%

Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts

et al. 2020

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“…In the literature, HLA-A * 01, HLA-C * 05, and HLA-C * 07 have been shown to be positively associated with survival of melanoma patients (Paschen et al, 2005;Campillo et al, 2006;Zhu et al, 2012), whereas HLA-B * 14, HLA-A * 24, HLA-A * 31, HLA-C * 14, and HLA-B * 13 are negatively associated with survival of melanoma patients (Marincola et al, 1995;Kawakami et al, 2000;Akiyama et al, 2005;Kandilarova et al, 2016;Rogel et al, 2019). Apart from these, HLA-DRB1 * 07 has been shown to be negatively associated with patient survival in other cancers such as lung cancer, cervical cancer, and breast cancer (Ferreiro-Iglesias et al, 2018;Hu et al, 2018;Spraggs et al, 2018). Further, in the current study, a parameter RS was computed to evaluate the cumulative effect of the presence of SF and SU superalleles in patients.…”

Section: Discussionmentioning

confidence: 99%

Computing Skin Cutaneous Melanoma Outcome From the HLA-Alleles and Clinical Characteristics

et al. 2020

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Human leukocyte antigen (HLA) are essential components of the immune system that stimulate immune cells to provide protection and defense against cancer. Thousands of HLA alleles have been reported in the literature, but only a specific set of HLA alleles are present in an individual. The capability of the immune system to recognize cancer-associated mutations depends on the presence of a particular set of alleles, which elicit an immune response to fight against cancer. Therefore, the occurrence of specific HLA alleles affects the survival outcome of cancer patients. In the current study, prediction models were developed, using 401 cutaneous melanoma patients, to predict the overall survival (OS) of patients using their clinical data and HLA alleles. We observed that the presence of certain favorable superalleles like HLA-B * 55 (HR = 0.15, 95% CI 0.034-0.67), HLA-A * 01 (HR = 0.5, 95% CI 0.3-0.8), is responsible for the improved OS. In contrast, the presence of certain unfavorable superalleles such as HLA-B * 50 (HR = 2.76, 95% CI 1.284-5.941), HLA-DRB1 * 12 (HR = 3.44, 95% CI 1.64-7.2) is responsible for the poor survival. We developed prediction models using key 14 HLA superalleles, demographic, and clinical characteristics for predicting high-risk cutaneous melanoma patients and achieved HR = 4.52 (95% CI 3.088-6.609, p-value = 8.01E-15). Eventually, we also provide a web-based service to the community for predicting the risk status in cutaneous melanoma patients (https://webs.iiitd.edu.in/raghava/skcmhrp/).

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“…The HLA region is critical for innate and adaptive immune response and has a complex relationship with cancer risk. Heterogeneous associations with HLA haplotypes have been reported for different subtypes of NHL 50 and lung cancer, 51 suggesting that relevant risk variants are likely to differ within, as well as between, cancers. Studies have further demonstrated that somatic mutation profiles are associated with HLA class I 52 and class II alleles.…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Study Detects Novel Genetic Risk Variants and Shared Genetic Basis in Two Large Cohorts

Rashkin¹,

Graff

Kachuri³

et al. 2019

Preprint

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Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. However, no studies have investigated pan-cancer pleiotropy within single, well-defined populations unselected for phenotype. We undertook novel genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (413,870 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detected 21 novel genome-wide significant risk variants. In addition, numerous cancer sites exhibited clear heritability.Investigations of pleiotropy identified 12 cancer pairs exhibiting either positive or negative genetic correlations and 43 pleiotropic loci. We identified 158 pleiotropic variants, many of which were enriched for regulatory elements and influenced cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.

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Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Cited by 47 publications

References 43 publications

Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts

Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts

Computing Skin Cutaneous Melanoma Outcome From the HLA-Alleles and Clinical Characteristics

Pan-Cancer Study Detects Novel Genetic Risk Variants and Shared Genetic Basis in Two Large Cohorts

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