TY - JOUR
T1 - Two BRM promoter insertion polymorphisms increase the risk of early-stage upper aerodigestive tract cancers
AU - Wong, Kit M.an
AU - Qiu, Xiaoping
AU - Cheng, Dangxiao
AU - Azad, Abul K.alam
AU - Habbous, Steven
AU - Palepu, Prakruthi
AU - Mirshams, Maryam
AU - Patel, Devalben
AU - Chen, Zhuo
AU - Roberts, Heidi
AU - Knox, Jennifer
AU - Marquez, Stephanie
AU - Wong, Rebecca
AU - Darling, Gail
AU - Waldron, John
AU - Goldstein, David
AU - Leighl, Natasha
AU - Shepherd, Frances A.
AU - Tsao, Ming
AU - Der, Sandy
AU - Reisman, David
AU - Liu, Geoffrey
N1 - Publisher Copyright:
© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion-deletion polymorphisms, BRM-741 and BRM-1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case-control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.e., lung, esophageal, head and neck), a group of early-stage malignancies in which molecular and genetic etiologic factors are poorly understood. The effects of various clinical factors on this association were also studied. We analyzed 562 cases of early-stage UADT cancers and 993 matched healthy controls. The double homozygous BRM promoter variants were associated with a significantly increased risk of early stage UADT cancers (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.7-3.8). This association was observed in lung (aOR, 2.61; 95% CI, 1.5-4.9) and head and neck (aOR, 2.75; 95% CI, 1.4-5.6) cancers, but not significantly in esophageal cancer (aOR, 1.66; 95% CI, 0.7-5.8). There was a nonsignificant trend for increased risk in the heterozygotes or single homozygotes. The relationship between the BRM polymorphisms and early-stage UADT cancers was independent of age, sex, smoking status, histology, and clinical stage. These findings suggest that the BRM promoter double insertion homozygotes may be associated with an increased risk of early-stage UADT cancers independent of smoking status and histology, which must be further validated in other populations.
AB - Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion-deletion polymorphisms, BRM-741 and BRM-1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case-control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.e., lung, esophageal, head and neck), a group of early-stage malignancies in which molecular and genetic etiologic factors are poorly understood. The effects of various clinical factors on this association were also studied. We analyzed 562 cases of early-stage UADT cancers and 993 matched healthy controls. The double homozygous BRM promoter variants were associated with a significantly increased risk of early stage UADT cancers (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.7-3.8). This association was observed in lung (aOR, 2.61; 95% CI, 1.5-4.9) and head and neck (aOR, 2.75; 95% CI, 1.4-5.6) cancers, but not significantly in esophageal cancer (aOR, 1.66; 95% CI, 0.7-5.8). There was a nonsignificant trend for increased risk in the heterozygotes or single homozygotes. The relationship between the BRM polymorphisms and early-stage UADT cancers was independent of age, sex, smoking status, histology, and clinical stage. These findings suggest that the BRM promoter double insertion homozygotes may be associated with an increased risk of early-stage UADT cancers independent of smoking status and histology, which must be further validated in other populations.
KW - BRM
KW - cancer risk
KW - case-control study
KW - esophageal cancer
KW - genetic polymorphisms
KW - head and neck cancer
KW - lung cancer
KW - upper aerodigestive tract cancers
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U2 - 10.1002/cam4.201
DO - 10.1002/cam4.201
M3 - Article
C2 - 24519853
AN - SCOPUS:84924838016
SN - 2045-7634
VL - 3
SP - 426
EP - 433
JO - Cancer Medicine
JF - Cancer Medicine
IS - 2
ER -