TP53 Polymorphisms and Colorectal Cancer Risk in Patients with Lynch Syndrome in Taiwan: A Retrospective Cohort Study

Abstract

Background and AimTP53 encodes p53, which has a crucial role in modulating genes that regulate defense against cancer development. This study investigated whether TP53 polymorphisms are associated with colorectal cancer (CRC) in patients with Lynch syndrome and whether TP53 interacts with lifestyle factors to modify CRC risk.MethodsWe identified 260 MLH1 and MSH2 germline mutation carriers from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association of TP53 polymorphisms with CRC development.ResultsThe carriers of the variant C allele of rs1042522 were associated with a decreased CRC risk (GC genotype: HR = 0.35, 95% CI = 0.14–0.86; CC genotype: HR = 0.28, 95% CI = 0.13–0.57). In addition, the dominant model of rs1042522 was associated with a decreased CRC risk (HR = 0.32, 95% CI = 0.15–0.67). The CRC risk was decreased in carriers with the CT and TT genotypes of rs12947788 (HR = 0.20, 95% CI = 0.08–0.46 and HR = 0.25, 95% CI = 0.09–0.65, respectively). Moreover, the dominant model of rs12947788 was significantly associated with a decreased CRC risk (HR = 0.21, 95% CI = 0.09–0.46). A haplotype analysis indicated that compared with the most common GC haplotype, the CT haplotype was associated with a decreased CRC risk (HR = 0.26, 95% CI = 0.11–0.59). However, no significant interaction was observed between TP53 polymorphisms and lifestyle factors.ConclusionThe study results revealed that the rs1042522 genotype with the C allele and the rs12947788 genotype with the T allele in TP53 were associated with a decreased CRC risk in patients with Lynch syndrome in Taiwan.

Polymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome

“…Patients suspected of HNPCC were recruited into the Amsterdam criteria family registry using the guidelines adopted from Amsterdam criteria II as previously described (Kamiza et al., , , ; Tang et al., ). One thousand and fourteen patients and their relatives from 135 Lynch syndrome families were recruited.…”

“…Probands who fulfilled Amsterdam criteria were screened for germline mutation in MLH1 and MSH2 . Genetic analyses were also performed to family members of probands as previously described (Kamiza et al., , , ; Tang et al., ). Of these probands and family members, 303 were identified as having germline mutation.…”

“…Nurses were trained to conduct interviews. Clinical data from probands were collected from May 2002 onwards as previously described (Kamiza et al., , , ). In addition, patients with Lynch syndrome were interviewed using structured questionnaire, which included demographic factors, dietary factors, lifestyle factors, medical, and family histories of cancer.…”

“…Genotyping was performed using Sequenom iPLEX MassARRAY (Sequenom, Inc., San Diego, CA, USA). Matrix‐assisted laser desorption ionization time of flight (MALDI‐TOF) spectroscopy was performed using the Sequenom MassARRAY platform and iPLEX GOLD chemistry as described in our previous studies (Kamiza et al., , , ). We added 10 ng of template DNA in polymerase chain reaction (PCR) mixture containing Qiagen HotStarTaq.…”

The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features

“…30 Furthermore, Akulevich et al found the correlation of rs1042522 with the higher risk of radiogenic PTC in Caucasians (OR = 1.80, 95% CI 1.06-2.36). 17 The protective effects of GC (Arg/Pro) genotype against retinoblastoma 21 and C (Pro) allele against endometrial cancer 31 and colorectal cancer 32 have been reported previously. Dehghan et al found no significant difference between Arg72pro genotypes in Iranian patients with differentiated thyroid cancer and control group.…”