Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma

Abstract

Our data present, for the first time, evidence that inherited OGG1 c.977C>G; XRCC1 c.-77T>C, c.580C>T, c.839G>A and c.1196G>A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes.

Effects of the Ser326Cys Polymorphism in the DNA Repair OGG1 Gene on Cancer, Cardiovascular, and All-Cause Mortality in the PREDIMED Study: Modulation by Diet

“…Therefore, it can be assumed that some associations found in the present study, mainly those obtained in subgroup analyses, may be overestimated due to the low number of Cys326Cys carriers. Supporting a true association, the current study's results are consistent with dozens of previous studies in animal models that show harmful health effects associated with a reduced DNA repair capacity of the variants in the OGG1 gene 7,[48][49][50][51][52] They are also consistent with work in humans that associate the Cys326 variant with a higher risk of cancer [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] as well as other diseases 2,33,[53][54][55] . However, as far as we know, no previous study has estimated the influence of this polymorphism on total mortality.…”

“…In this study the influence of the OGG1-rs1052133 (Ser326Cys) polymorphism on total and cause-specific mortality, including cancer and cardiovascular mortality, has been longitudinally investigated in a cohort of older participants in the PREDIMED study. This polymorphism, in which the Cys326Cys genotype has been associated with a lower damage repair capacity in DNA [15][16][17] , has also been associated with a higher risk of cancer and other diseases related to DNA repair in many studies 7,[18][19][20][21][22][23][24][25][26][27] . However, no previous study has jointly analyzed the impact of this polymorphism on total mortality and in a comparative manner on cancer and cardiovascular mortality in the same population.…”

“…In a subsample of this population 56 , higher levels of the DNA-damaged product 8-oxo-7′8′-dihydro-2′-deoxyguanosine Although several studies have analyzed the influence of the OGG1-rs1052133 on cancer incidence or prevalence [19][20][21][22][23][24][25][26][27] , no previous study at the population level has analyzed the association of such polymorphism with cancer mortality. Some studies have analyzed the influence of the OGG1-rs1052133 polymorphism on the survival or prognosis of selected groups of patients receiving cancer treatment 57,58 , but there are no estimates of mortality rates in a general population cohort. Although in our cohort at high cardiovascular risk deaths from cancer outnumbered those from cardiovascular disease, no association between the Cys326Cys genotype and cancer mortality was observed in the whole population.…”

“…The deactivation of the OGG1 gene or the presence of a less active variant such as the Cys326 may lead to a higher risk of cancer and oxidation-related pathologies 7,13,18 . Consequently, this polymorphism has been analyzed as a risk factor in several cancers [19][20][21][22][23][24][25] (i.e., breast, prostate, lung, colorectal, aero digestive, gastric, bladder). The results of meta-analyses for each location are heterogeneous [21][22][23][24][25] , but where there is more consensus is in the significant association of the Ser326Cys polymorphism with greater overall risk of cancer when the different locations are pooled 26,27 . Thus, Zou et al 26 in a meta-analysis including 152 case-control studies, concluded that the Cys variant was strongly associated with higher cancer risk.…”

The polymorphisms of miRNA‐binding site in MLH3 and ERCC1 were linked to the risk of colorectal cancer in a case–control study

“…Generally speaking, six proteins (hMSH2, hMSH3, hMSH6, hMLH1, hMLH3, hPMS1, and hPMS2) participate in human MMR pathway . However, NER is a major DNA repair mechanism, which can contribute to the removal of bulky adducts and DNA cross‐links to maintain cellular genetic stability . BER pathway can handle DNA lesions that do not significantly distort the double helix.…”