Prognostic relevance of caspase 8 -652 6N InsDel and Asp302His polymorphisms for breast cancer

Abstract

BackgroundThe minor allele of two caspase 8 polymorphisms, namely CASP8 -652 6N InsDel (rs3834129) and CASP8 Asp302His (rs1045485), were repeatedly associated with reduced breast cancer susceptibility. Contrarily, the presence of the -652 6N Del or the CASP8 302His variant was reported to be an unfavorable prognostic factor in colorectal cancer or neuroblastoma. However, prognostic relevance of these genetic variants for breast cancer is completely unknown and is therefore adressed by the current study.MethodsGenotyping was performed by pyrosequencing. Caspase 8 mRNA expression was quantified by comparative RT-qPCR.ResultsWe observed an allele-dose dependent association between CASP8 -652 6N InsDel and caspase 8 mRNA expression in breast cancer tissue, with homozygous deletion carriers showing lowest relative caspase 8 expression (p = 0.0131). Intriguingly, the presence of the -652 6N Del or the 302His variant was shown to be a negative prognostic factor for breast cancer in terms of an allele-dose dependent influence on overall survival (OS, p = 0.0018, p = 0.0150, respectively). Moreover, both polymorphisms were independent predictors of OS after adjusting for co-variats (p = 0.007, p = 0.037, respectively). Prognostic relevance of both polymorphisms were confirmed to be independent from each other and combined analysis of diplotypes revealed an additive influence upon OS (p = 0.0002).ConclusionThis is the first report, showing negative and independent prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast cancer. Our data provide rationale to further validate clinical utility of these polymorphisms for breast cancer and to extend this investigation to a broad scope of other malignancies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2662-x) contains supplementary material, which is available to authorized users.

CASP8-652 6N insertion/deletion polymorphism and overall cancer risk: evidence from 49 studies

“…After scanning titles and abstracts, 67 articles about unrelated topics were excluded. We further excluded 12 articles: eight were meta-analyses [ 14 – 21 ], three were case only studies [ 22 – 24 ], and one deviated from HWE [ 25 ]. Articles incorporating several ethnic groups or cancer types were separated into corresponding independent studies.…”

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China

“…Although its etiology is not clear, we know that it is not only a skin-restricted disease but also a systemic inflammatory immune disorder which is influenced by various genetic and environmental factors [3]. As with many autoimmune diseases, abnormal apoptosis has important implications in psoriasis biology [4, 5]. The data show that, in addition to the hyperproliferation of keratinocytes, deceleration in keratinocyte apoptosis is also a significant pathological change observed in psoriasis [6–8].…”

“…Apoptosis, a unique physiological process genetically controlling programmed cell death, is essential for maintaining normal tissue homeostasis, cell differentiation, and development [4]. In the skin, the death of apoptotic cells regulates keratinocyte proliferation and the formation of the stratum corneum [10].…”

Analysis of 12 variants in the development of gastric and colorectal cancers

“…These genes and polymorphisms have been studied in association with various types of cancer in different populations, e.g , breast cancer[ 15 - 19 ], bladder cancer[ 20 ], endometrial cancer[ 21 ], acute lymphoblastic leukemia[ 22 ], chronic lymphoblastic leukemia[ 23 ], oral carcinoma[ 24 , 25 ], lung cancer[ 26 ], nasopharyngeal cancer[ 27 ], thyroid cancer[ 28 ], hepatocellular carcinoma[ 29 ], GC[ 30 - 39 ] and CRC[ 40 - 50 ]. Therefore, these markers were chosen based on the importance of each gene as a potential influencing factor in the susceptibility of tumor development.…”