TP53 polymorphisms and colorectal cancer risk in patients with lynch syndrome in Taiwan: A retrospective cohort study

Abram Bunya Kamiza, Ling Ling Hsieh, Reiping Tang, Huei Tzu Chien, Chih Hsiung Lai, Li Ling Chiu, Tsai Ping Lo, Kuan Yi Hung, Jeng Fu You, Wen Chang Wang, Chao A. Hsiung, Chih Ching Yeh

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Abstract

Background and aim: TP53 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. Methods: We 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. Results: The 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. Conclusion: The 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.

Original languageEnglish
Article numbere0167354
JournalPLoS One
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

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Hereditary Nonpolyposis Colorectal Neoplasms
Polymorphism
colorectal neoplasms
cohort studies
Taiwan
Colorectal Neoplasms
Hazards
Cohort Studies
Retrospective Studies
genetic polymorphism
confidence interval
Confidence Intervals
Genotype
Haplotypes
genotype
Alleles
Odds Ratio
haplotypes
alleles
Life Style

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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TP53 polymorphisms and colorectal cancer risk in patients with lynch syndrome in Taiwan : A retrospective cohort study. / Kamiza, Abram Bunya; Hsieh, Ling Ling; Tang, Reiping; Chien, Huei Tzu; Lai, Chih Hsiung; Chiu, Li Ling; Lo, Tsai Ping; Hung, Kuan Yi; You, Jeng Fu; Wang, Wen Chang; Hsiung, Chao A.; Yeh, Chih Ching.

In: PLoS One, Vol. 11, No. 12, e0167354, 01.12.2016.

Research output: Contribution to journalArticle

Kamiza, AB, Hsieh, LL, Tang, R, Chien, HT, Lai, CH, Chiu, LL, Lo, TP, Hung, KY, You, JF, Wang, WC, Hsiung, CA & Yeh, CC 2016, 'TP53 polymorphisms and colorectal cancer risk in patients with lynch syndrome in Taiwan: A retrospective cohort study', PLoS One, vol. 11, no. 12, e0167354. https://doi.org/10.1371/journal.pone.0167354
Kamiza, Abram Bunya ; Hsieh, Ling Ling ; Tang, Reiping ; Chien, Huei Tzu ; Lai, Chih Hsiung ; Chiu, Li Ling ; Lo, Tsai Ping ; Hung, Kuan Yi ; You, Jeng Fu ; Wang, Wen Chang ; Hsiung, Chao A. ; Yeh, Chih Ching. / TP53 polymorphisms and colorectal cancer risk in patients with lynch syndrome in Taiwan : A retrospective cohort study. In: PLoS One. 2016 ; Vol. 11, No. 12.
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abstract = "Background and aim: TP53 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. Methods: We 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. Results: The 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. Conclusion: The 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.",
author = "Kamiza, {Abram Bunya} and Hsieh, {Ling Ling} and Reiping Tang and Chien, {Huei Tzu} and Lai, {Chih Hsiung} and Chiu, {Li Ling} and Lo, {Tsai Ping} and Hung, {Kuan Yi} and You, {Jeng Fu} and Wang, {Wen Chang} and Hsiung, {Chao A.} and Yeh, {Chih Ching}",
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T1 - TP53 polymorphisms and colorectal cancer risk in patients with lynch syndrome in Taiwan

T2 - A retrospective cohort study

AU - Kamiza, Abram Bunya

AU - Hsieh, Ling Ling

AU - Tang, Reiping

AU - Chien, Huei Tzu

AU - Lai, Chih Hsiung

AU - Chiu, Li Ling

AU - Lo, Tsai Ping

AU - Hung, Kuan Yi

AU - You, Jeng Fu

AU - Wang, Wen Chang

AU - Hsiung, Chao A.

AU - Yeh, Chih Ching

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N2 - Background and aim: TP53 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. Methods: We 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. Results: The 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. Conclusion: The 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.

AB - Background and aim: TP53 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. Methods: We 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. Results: The 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. Conclusion: The 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.

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