Risk factors associated with colorectal cancer in a subset of patients with mutations in MLH1 and MSH2 in Taiwan fulfilling the Amsterdam II criteria for Lynch syndrome

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

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Abstract

Background and Aim: Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations. Methods: In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence. Results: Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34); however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88). The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55) and 0.54 (95% CI = 0.34-0.83) among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27) than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58) compared with those with blood group type O. Conclusion: The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.

Original languageEnglish
Article numbere0130018
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 8 2015

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Lynch Syndrome II
Set theory
colorectal neoplasms
Taiwan
Colorectal Neoplasms
risk factors
Germ-Line Mutation
mutation
Mutation
Hazards
confidence interval
Confidence Intervals
germ cells
Blood Group Antigens
blood groups
Occupations
nationalities and ethnic groups
Hereditary Nonpolyposis Colorectal Neoplasms
physical activity
Odds Ratio

ASJC Scopus subject areas

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

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Risk factors associated with colorectal cancer in a subset of patients with mutations in MLH1 and MSH2 in Taiwan fulfilling the Amsterdam II criteria for Lynch syndrome. / Kamiza, Abram Bunya; Hsieh, Ling Ling; Tang, Reiping; Chien, Huei Tzu; Lai, Chih Hsiung; Chiu, Li Ling; Lo, Tsai Ping; Hung, Kuan Yi; Wang, Chun Yi; You, Jeng Fu; Hsiung, Chao A.; Yeh, Chih Ching.

In: PLoS One, Vol. 10, No. 6, e0130018, 08.06.2015.

Research output: Contribution to journalArticle

Kamiza, Abram Bunya ; Hsieh, Ling Ling ; Tang, Reiping ; Chien, Huei Tzu ; Lai, Chih Hsiung ; Chiu, Li Ling ; Lo, Tsai Ping ; Hung, Kuan Yi ; Wang, Chun Yi ; You, Jeng Fu ; Hsiung, Chao A. ; Yeh, Chih Ching. / Risk factors associated with colorectal cancer in a subset of patients with mutations in MLH1 and MSH2 in Taiwan fulfilling the Amsterdam II criteria for Lynch syndrome. In: PLoS One. 2015 ; Vol. 10, No. 6.
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title = "Risk factors associated with colorectal cancer in a subset of patients with mutations in MLH1 and MSH2 in Taiwan fulfilling the Amsterdam II criteria for Lynch syndrome",
abstract = "Background and Aim: Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations. Methods: In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95{\%} confidence intervals (CIs) to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence. Results: Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95{\%} CI = 1.09-2.34); however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95{\%} CI = 0.41-0.88). The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95{\%} CI = 1.16-2.55) and 0.54 (95{\%} CI = 0.34-0.83) among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95{\%} CI = 1.07-2.27) than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95{\%} CI = 1.06-6.58) compared with those with blood group type O. Conclusion: The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.",
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 Wang, {Chun Yi} and You, {Jeng Fu} and Hsiung, {Chao A.} and Yeh, {Chih Ching}",
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T1 - Risk factors associated with colorectal cancer in a subset of patients with mutations in MLH1 and MSH2 in Taiwan fulfilling the Amsterdam II criteria for Lynch syndrome

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 - Wang, Chun Yi

AU - You, Jeng Fu

AU - Hsiung, Chao A.

AU - Yeh, Chih Ching

PY - 2015/6/8

Y1 - 2015/6/8

N2 - Background and Aim: Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations. Methods: In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence. Results: Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34); however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88). The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55) and 0.54 (95% CI = 0.34-0.83) among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27) than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58) compared with those with blood group type O. Conclusion: The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.

AB - Background and Aim: Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations. Methods: In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence. Results: Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34); however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88). The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55) and 0.54 (95% CI = 0.34-0.83) among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27) than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58) compared with those with blood group type O. Conclusion: The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.

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