Marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability

Mingyang Song, Reiko Nishihara, Kana Wu, Zhi R ong Qian, Sun A. Kim, Yasutaka Sukawa, Kosuke Mima, Kentaro Inamura, Atsuhiro Masuda, Juhong Yang, Charles S. Fuchs, Edward L. Giovannucci, Shuji Ogino, Andrew T. Chan

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Abstract

METHODS: We investigated whether the association between marine ω-3 PUFAs and CRC varies by MSI-defined subtypes of tumors in the Nurses' Health Study and Health Professionals Follow-up Study. We documented and classified 1125 CRC cases into either MSI-high tumors, in which 30% or more of the 10 microsatellite markers demonstrated instability, or microsatellite-stable (MSS) tumors. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MSS tumors and MSI-high tumors in relation to marine ω-3 PUFA intake. All statistical tests were two-sided.

RESULTS: Marine ω-3 PUFA intake was not associated with overall incidence of CRC. However, a statistically significant difference was detected by MSI status (P heterogeneity = .02): High marine ω-3 PUFA intake was associated with a lower risk of MSI-high tumors (comparing ≥0.30g/d with <0.10g/d: multivariable HR = 0.54, 95% CI = 0.35 to 0.83, P linearity = .03) but not MSS tumors (HR = 0.97, 95% CI = 0.78 to 1.20, P linearity = .28). This differential association appeared to be independent of CpG island methylator phenotype and BRAF mutation status.

CONCLUSIONS: High marine ω-3 PUFA intake is associated with lower risk of MSI-high CRC but not MSS tumors, suggesting a potential role of ω-3 PUFAs in protection against CRC through DNA mismatch repair. Further research is needed to confirm our findings and elucidate potential underlying mechanisms.

BACKGROUND: Chronic inflammation is involved in the development of colorectal cancer (CRC) and microsatellite instability (MSI), a distinct phenotype of CRC. Experimental evidence indicates an anti-inflammatory and antineoplastic effect of marine ω-3 polyunsaturated fatty acids (PUFAs). However, epidemiologic data remain inconclusive.

Original languageEnglish
JournalJournal of the National Cancer Institute
Volume107
Issue number4
DOIs
Publication statusPublished - 2015 Apr 1
Externally publishedYes

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Microsatellite Instability
Unsaturated Fatty Acids
Colorectal Neoplasms
Microsatellite Repeats
Neoplasms
Confidence Intervals
Phenotype
CpG Islands
DNA Mismatch Repair
Health
Proportional Hazards Models
Antineoplastic Agents
Anti-Inflammatory Agents
Nurses
Inflammation
Mutation
Incidence

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability. / Song, Mingyang; Nishihara, Reiko; Wu, Kana; Qian, Zhi R ong; Kim, Sun A.; Sukawa, Yasutaka; Mima, Kosuke; Inamura, Kentaro; Masuda, Atsuhiro; Yang, Juhong; Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.

In: Journal of the National Cancer Institute, Vol. 107, No. 4, 01.04.2015.

Research output: Contribution to journalArticle

Song, M, Nishihara, R, Wu, K, Qian, ZRO, Kim, SA, Sukawa, Y, Mima, K, Inamura, K, Masuda, A, Yang, J, Fuchs, CS, Giovannucci, EL, Ogino, S & Chan, AT 2015, 'Marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability', Journal of the National Cancer Institute, vol. 107, no. 4. https://doi.org/10.1093/jnci/djv007
Song, Mingyang ; Nishihara, Reiko ; Wu, Kana ; Qian, Zhi R ong ; Kim, Sun A. ; Sukawa, Yasutaka ; Mima, Kosuke ; Inamura, Kentaro ; Masuda, Atsuhiro ; Yang, Juhong ; Fuchs, Charles S. ; Giovannucci, Edward L. ; Ogino, Shuji ; Chan, Andrew T. / Marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 4.
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abstract = "METHODS: We investigated whether the association between marine ω-3 PUFAs and CRC varies by MSI-defined subtypes of tumors in the Nurses' Health Study and Health Professionals Follow-up Study. We documented and classified 1125 CRC cases into either MSI-high tumors, in which 30{\%} or more of the 10 microsatellite markers demonstrated instability, or microsatellite-stable (MSS) tumors. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95{\%} confidence intervals (CIs) of MSS tumors and MSI-high tumors in relation to marine ω-3 PUFA intake. All statistical tests were two-sided.RESULTS: Marine ω-3 PUFA intake was not associated with overall incidence of CRC. However, a statistically significant difference was detected by MSI status (P heterogeneity = .02): High marine ω-3 PUFA intake was associated with a lower risk of MSI-high tumors (comparing ≥0.30g/d with <0.10g/d: multivariable HR = 0.54, 95{\%} CI = 0.35 to 0.83, P linearity = .03) but not MSS tumors (HR = 0.97, 95{\%} CI = 0.78 to 1.20, P linearity = .28). This differential association appeared to be independent of CpG island methylator phenotype and BRAF mutation status.CONCLUSIONS: High marine ω-3 PUFA intake is associated with lower risk of MSI-high CRC but not MSS tumors, suggesting a potential role of ω-3 PUFAs in protection against CRC through DNA mismatch repair. Further research is needed to confirm our findings and elucidate potential underlying mechanisms.BACKGROUND: Chronic inflammation is involved in the development of colorectal cancer (CRC) and microsatellite instability (MSI), a distinct phenotype of CRC. Experimental evidence indicates an anti-inflammatory and antineoplastic effect of marine ω-3 polyunsaturated fatty acids (PUFAs). However, epidemiologic data remain inconclusive.",
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T1 - Marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability

AU - Song, Mingyang

AU - Nishihara, Reiko

AU - Wu, Kana

AU - Qian, Zhi R ong

AU - Kim, Sun A.

AU - Sukawa, Yasutaka

AU - Mima, Kosuke

AU - Inamura, Kentaro

AU - Masuda, Atsuhiro

AU - Yang, Juhong

AU - Fuchs, Charles S.

AU - Giovannucci, Edward L.

AU - Ogino, Shuji

AU - Chan, Andrew T.

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N2 - METHODS: We investigated whether the association between marine ω-3 PUFAs and CRC varies by MSI-defined subtypes of tumors in the Nurses' Health Study and Health Professionals Follow-up Study. We documented and classified 1125 CRC cases into either MSI-high tumors, in which 30% or more of the 10 microsatellite markers demonstrated instability, or microsatellite-stable (MSS) tumors. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MSS tumors and MSI-high tumors in relation to marine ω-3 PUFA intake. All statistical tests were two-sided.RESULTS: Marine ω-3 PUFA intake was not associated with overall incidence of CRC. However, a statistically significant difference was detected by MSI status (P heterogeneity = .02): High marine ω-3 PUFA intake was associated with a lower risk of MSI-high tumors (comparing ≥0.30g/d with <0.10g/d: multivariable HR = 0.54, 95% CI = 0.35 to 0.83, P linearity = .03) but not MSS tumors (HR = 0.97, 95% CI = 0.78 to 1.20, P linearity = .28). This differential association appeared to be independent of CpG island methylator phenotype and BRAF mutation status.CONCLUSIONS: High marine ω-3 PUFA intake is associated with lower risk of MSI-high CRC but not MSS tumors, suggesting a potential role of ω-3 PUFAs in protection against CRC through DNA mismatch repair. Further research is needed to confirm our findings and elucidate potential underlying mechanisms.BACKGROUND: Chronic inflammation is involved in the development of colorectal cancer (CRC) and microsatellite instability (MSI), a distinct phenotype of CRC. Experimental evidence indicates an anti-inflammatory and antineoplastic effect of marine ω-3 polyunsaturated fatty acids (PUFAs). However, epidemiologic data remain inconclusive.

AB - METHODS: We investigated whether the association between marine ω-3 PUFAs and CRC varies by MSI-defined subtypes of tumors in the Nurses' Health Study and Health Professionals Follow-up Study. We documented and classified 1125 CRC cases into either MSI-high tumors, in which 30% or more of the 10 microsatellite markers demonstrated instability, or microsatellite-stable (MSS) tumors. Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of MSS tumors and MSI-high tumors in relation to marine ω-3 PUFA intake. All statistical tests were two-sided.RESULTS: Marine ω-3 PUFA intake was not associated with overall incidence of CRC. However, a statistically significant difference was detected by MSI status (P heterogeneity = .02): High marine ω-3 PUFA intake was associated with a lower risk of MSI-high tumors (comparing ≥0.30g/d with <0.10g/d: multivariable HR = 0.54, 95% CI = 0.35 to 0.83, P linearity = .03) but not MSS tumors (HR = 0.97, 95% CI = 0.78 to 1.20, P linearity = .28). This differential association appeared to be independent of CpG island methylator phenotype and BRAF mutation status.CONCLUSIONS: High marine ω-3 PUFA intake is associated with lower risk of MSI-high CRC but not MSS tumors, suggesting a potential role of ω-3 PUFAs in protection against CRC through DNA mismatch repair. Further research is needed to confirm our findings and elucidate potential underlying mechanisms.BACKGROUND: Chronic inflammation is involved in the development of colorectal cancer (CRC) and microsatellite instability (MSI), a distinct phenotype of CRC. Experimental evidence indicates an anti-inflammatory and antineoplastic effect of marine ω-3 polyunsaturated fatty acids (PUFAs). However, epidemiologic data remain inconclusive.

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