DNA Damage and Repair Capacity in Patients With Lung Cancer: Prediction of Multiple Primary Tumors

Orlow, Irene; Park, Bernard J.; Mujumdar, Urvi; Patel, Himali; Siu-Lau, Puiki; Clas, Brian; Downey, Robert J.; Flores, Raja M.; Bains, Manjit S.; Rizk, Nabil P.; Domínguez, Gemma; Jani, Jen; Berwick, Marianne; Begg, Colin B.; Kris, Mark G.; Rusch, Valerie W.

doi:10.1200/jco.2007.13.2654

Cited by 59 publications

(45 citation statements)

References 38 publications

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“…The study of Schmezer et al did not detect any significant difference between the levels of baseline DNA damage in lymphocytes of lung cancer patients and healthy individuals but found an increased sensitivity of lymphocytes to bleomycin and decreased DNA repair capacity in cancer patients [20]. The deficient DNA repair in lymphocytes of lung, head and neck cancer patients also has been shown by other researchers [4, 5, 8, 9]. It should be mentioned that the concentration of bleomycin (20 μg/ml) recommended by Schmezer et al, which we also used in our study, caused DNA damage at saturation level of the assay.…”

Section: Discussionmentioning

confidence: 82%

DNA repair deficiency in peripheral blood lymphocytes of endometrial cancer patients with a family history of cancer

et al. 2014

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BackgroundIndividual susceptibility to endogenous and/or exogenous DNA damage depends on DNA repair efficiency and can be evaluated using the comet assay with bleomycin as genotoxic agent. The aim of the study was to evaluate baseline and bleomycin-induced DNA damage and DNA repair capacity in peripheral blood lymphocytes (PBLs) of endometrial cancer (EC) patients considering a family history of cancer.MethodsDNA damage was analyzed in PBLs of 45 EC patients compared to a control group of 10 healthy women, using the comet assay. The level of DNA damage was determined by the% tail DNA.ResultsThe level of baseline DNA damage in PBLs of EC patients was significantly higher (% DNA in tail 9.31 ± 15.32) than in healthy women (% DNA in tail 3.41 ± 4.71) (P <0.01). PBLs of EC patients repaired less bleomycin-induced DNA damage (removed% DNA in tail 63.94 ± 20.92) than PBLs of healthy individuals (removed% DNA in tail 80.24 ± 3.03) (P <0.001). Efficiency of DNA repair in PBLs of EC patients depended on the family history of cancer. The amount of restored damaged DNA was significantly lower (removed% DNA in tail 36.24 ± 14.05%) in EC patients with a family history of cancer compared to patients with sporadic EC (removed% DNA in tail 64.91 ± 19.36%) (P <0.004).ConclusionsLymphocytes of EC patients are characterized by an increased basal level of DNA damage as well as deficiency in DNA repair. DNA repair is less efficient in PBLs of EC patients with a family history of cancer compared to patients with sporadic cancer.

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Section: Discussionmentioning

confidence: 82%

DNA repair deficiency in peripheral blood lymphocytes of endometrial cancer patients with a family history of cancer

et al. 2014

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“…26 In the recent studies 24 hours of recovery time has been applied. 27,28 Shahidi et al 28 have reported that in healthy individuals no residual DNA damage has been observed after a 24-hour repair incubation of leukocytes exposed to radiation. In the present study, an incubation time of 24 hours was chosen to guarantee the completion of repair.…”

Section: Discussionmentioning

confidence: 97%

DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors

Dinçer¹,

Yüksel²,

Batar³

et al. 2015

Journal of Pediatric Hematology/Oncology

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Oxidative stress and defective DNA repair are major contributory factors in the initiation and progression of carcinogenesis. Chemotherapy and radiotherapy cause oxidative DNA damage, consume antioxidant capacity, and impair DNA repair activity. These effects of chemotherapy and radiotherapy may be contributory factors in the development of secondary malignancy in cancer survivors. Basal, H2O2-induced, and postrepair DNA damage; urinary 8-hydroxydeoxyguanosine level as a marker of oxidatively damaged DNA; and serum total antioxidant capacity were measured; XPD Lys751Gln, XRCC1 Arg399Gln, and XRCC1 Arg194Trp polymorphisms were analyzed in childhood acute lymphoblastic leukemia (ALL) survivors. Basal and H2O2-induced DNA damage were found to be higher in the ALL survivor group versus the control group, however, there was no significant difference between the other parameters. No association was found between the examined parameters and polymorphisms of XPD 751 and XRCC1 399 and both the groups. XRCC1 194Trp allele was found to be associated with a low level of postrepair DNA damage in the ALL survivors. In conclusion, basal DNA damage and susceptibility to oxidation are high in childhood ALL survivors. This situation which may easily lead to occurrence of a secondary cancer does not seem to be a result of deficient DNA repair.

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“…It has been reported that interindividual variation in DNA repair capacity may lead to increased predisposition to cancer 29. Abnormal mutagen sensitivity found in studies that indirectly assessed DNA repair capacity has been found in patients with head and neck, colorectal, and non-small-cell lung cancers, as well as in patients with multiple primaries of similar malignancies 30. In the present analysis, cancer survivors who were smokers had a higher risk of multiple primaries compared with nonsmokers, particularly for lung, colorectal, and prostate cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Individuals with hereditary nonpolyposis colorectal cancer with multiple primaries have an increased frequency of mismatch repair genes, such as hMSH2 and hMLH1 , leading to microsatellite instability 33. Mutagen sensitivity, found in studies that indirectly assessed DNA repair capacity, tends to occur in patients with head and neck, hereditary nonpolyposis colorectal, and non-small-cell lung cancers 30. In the present study, a strong family history of cancer reflecting a close relationship between first-degree relatives was statistically more common in patients with multiple primaries, especially those with three or more primaries, and in those with metachronous primaries, highly suggestive of inherited cancer predisposition gene mutations, especially among Caucasian patients.…”

Section: Discussionmentioning

confidence: 99%

Multiple neoplasms, single primaries, and patient survival

Amer¹

2014

CMAR

101

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BackgroundMultiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined.MethodsThis was a retrospective review of clinical data for all consecutive patients with histologically confirmed cancer, with emphasis on single versus multiple primary neoplasms. Second primaries discovered at the workup of the index (first) primary were termed simultaneous, if discovered within 6 months of the index primary were called synchronous, and if discovered after 6 months were termed metachronous.ResultsBetween 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies; these included two primaries (n=284), and three or more primaries (n=38). Forty-seven patients had synchronous primaries and 275 had metachronous primaries. Patients with multiple primaries were predominantly of Caucasian ancestry (91.0%), with a tendency to develop thrombosis (20.2%), had a strong family history of similar cancer (22.3%), and usually presented with earlier stage 0 through stage II disease (78.9%). When compared with 1,551 patients with a single primary, these figures were 8.9%, 15.6%, 18.3%, and 50.9%, respectively (P≤0.001). Five-year survival rates were higher for metachronous cancers (95%) than for synchronous primaries (59%) and single primaries (59%). The worst survival rate was for simultaneous concomitant multiple primaries, being a median of 1.9 years. The best survival was for patients with three or more primaries (median 10.9 years) and was similar to the expected survival for the age-matched and sex-matched general population (P=0.06991).ConclusionPatients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent clinical behavior with longer survival rates, possibly related to genetic predisposition.

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DNA Damage and Repair Capacity in Patients With Lung Cancer: Prediction of Multiple Primary Tumors

Cited by 59 publications

References 38 publications

DNA repair deficiency in peripheral blood lymphocytes of endometrial cancer patients with a family history of cancer

DNA repair deficiency in peripheral blood lymphocytes of endometrial cancer patients with a family history of cancer

DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors

Multiple neoplasms, single primaries, and patient survival

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