Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012

A matched case-control study

Jiajia Zhang, Charles Haines, Alastair J.M. Watson, Andrew R. Hart, Mary Jane Platt, Andrew Mark Pardoll, Sara Cosgrove, Kelly Gebo, Cynthia Louise Sears

Research output: Contribution to journalArticle

Abstract

Background: Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking. Objective: To assess the association between oral antibiotic use and CRC risk. Design: A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012. Results: 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)). Conclusion: Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.

Original languageEnglish (US)
JournalGut
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Case-Control Studies
Colorectal Neoplasms
Anti-Bacterial Agents
Colonic Neoplasms
Rectal Neoplasms
Dysbiosis
Tetracyclines
United Kingdom
Microbiota
Amoxicillin
Ampicillin
Rectum
Penicillins
Colon
Carcinogenesis
Research
Population
Neoplasms

Keywords

  • antibiotics
  • cancer risk
  • colorectal cancer
  • tumor location

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012 : A matched case-control study. / Zhang, Jiajia; Haines, Charles; Watson, Alastair J.M.; Hart, Andrew R.; Platt, Mary Jane; Pardoll, Andrew Mark; Cosgrove, Sara; Gebo, Kelly; Sears, Cynthia Louise.

In: Gut, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: A matched case-control study",
abstract = "Background: Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking. Objective: To assess the association between oral antibiotic use and CRC risk. Design: A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012. Results: 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95{\%} CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)). Conclusion: Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.",
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author = "Jiajia Zhang and Charles Haines and Watson, {Alastair J.M.} and Hart, {Andrew R.} and Platt, {Mary Jane} and Pardoll, {Andrew Mark} and Sara Cosgrove and Kelly Gebo and Sears, {Cynthia Louise}",
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T1 - Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012

T2 - A matched case-control study

AU - Zhang, Jiajia

AU - Haines, Charles

AU - Watson, Alastair J.M.

AU - Hart, Andrew R.

AU - Platt, Mary Jane

AU - Pardoll, Andrew Mark

AU - Cosgrove, Sara

AU - Gebo, Kelly

AU - Sears, Cynthia Louise

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Y1 - 2019/1/1

N2 - Background: Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking. Objective: To assess the association between oral antibiotic use and CRC risk. Design: A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012. Results: 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)). Conclusion: Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.

AB - Background: Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking. Objective: To assess the association between oral antibiotic use and CRC risk. Design: A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012. Results: 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)). Conclusion: Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.

KW - antibiotics

KW - cancer risk

KW - colorectal cancer

KW - tumor location

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