2845. Oral Antibiotic Use and Risk of Colorectal Cancer in the UK, 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 CRC risk is lacking. Methods A matched case–control study (incident CRC cases and up to 5 matched controls) was conducted in the Clinical Practice Research Datalink (CPRD; 1989–2012). The CRPD is validated as 92% and 99% sensitive and specific for CRC detection (98% PPV). Antibiotic exposure [categorical and continuous terms (spline)] was investigated for risk pattern, stratified by tumor location, using conditional logistic regression and adjusting for known confounders. Results In total, 28,980 CRC cases and 137,077 controls were identified. Oral antibiotic use increased risk of colon cancer in a dose-dependent fashion (Ptrend < 0.001), but effects differed by anatomic location. Colon cancer risk was greatest in the proximal colon and with antibiotics with anti-anaerobic activity (Figure 1). 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 odds ratio [AOR], 0.85, 95% CI 0.79–0.93) when compared with no antibiotic exposure. Nonlinearity models showed significantly increased colon cancer risk after minimal antibiotic use, but decreased rectum cancer risk with cumulative use of over 30 days (Figure 2). Penicillins, particularly ampicillin/amoxicillin, increased risk of colon cancer (AOR,1.09, [1.05–1.13]) whereas tetracyclines reduced risk for rectal cancer (AOR, 0.90, [0.84–0.97]). Significant interactions were detected between antibiotic use and tumor location (colon vs. rectum, Pinteraction < 0.001). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (AOR, 1.17, [1.06–1.31]). Conclusion We conclude that oral antibiotic use associates with increased colon cancer risk, particularly in the right colon, but a reduced risk for rectal cancer. This effect heterogeneity suggests unabsorbed antibiotics impact gut microbiota in the right colon to enhance carcinogenesis whereas antibiotic anti-inflammatory or anti-proliferative actions may yield an inverse effect on carcinogenesis in the rectum. Disclosures Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.

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Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study

Gut ◽

10.1136/gutjnl-2019-318593 ◽

2019 ◽

Vol 68 (11) ◽

pp. 1971-1978 ◽

Cited By ~ 24

Author(s):

Jiajia Zhang ◽

Charles Haines ◽

Alastair J M Watson ◽

Andrew R Hart ◽

Mary Jane Platt ◽

...

Keyword(s):

Colon Cancer ◽

Case Control Study ◽

Antibiotic Use ◽

Case Control ◽

Proximal Colon ◽

Oral Antibiotic ◽

Antibiotic Exposure ◽

Matched Case ◽

Matched Case Control Study ◽

Control Study

BackgroundMicrobiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking.ObjectiveTo assess the association between oral antibiotic use and CRC risk.DesignA 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.Results28 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)).ConclusionOral 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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Serum Lipids and the Risk of Gastrointestinal Malignancies in the Swedish AMORIS Study

Journal of Cancer Epidemiology ◽

10.1155/2012/792034 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 30

Author(s):

Wahyu Wulaningsih ◽

Hans Garmo ◽

Lars Holmberg ◽

Niklas Hammar ◽

Ingmar Jungner ◽

...

Keyword(s):

Rectal Cancer ◽

Colon Cancer ◽

Cancer Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Gastrointestinal Malignancies ◽

Colon Cancer Risk ◽

Colon And Rectal Cancer ◽

Increased Risk ◽

Lipid Components

Background. Metabolic syndrome has been linked to an increased cancer risk, but the role of dyslipidaemia in gastrointestinal malignancies is unclear. We aimed to assess the risk of oesophageal, stomach, colon, and rectal cancers using serum levels of lipid components.Methods. From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected 540,309 participants (> 20 years old) with baseline measurements of total cholesterol (TC), triglycerides (TG), and glucose of whom 84,774 had baseline LDL cholesterol (LDL), HDL cholesterol (HDL), apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Multivariate Cox proportional hazards regression was used to assess glucose and lipid components in relation to oesophageal, stomach, colon, and rectal cancer risk.Results. An increased risk of oesophageal cancer was observed in persons with high TG (e.g. HR: 2.29 (95% CI: 1.42–3.68) for the 4th quartile compared to the 1st) and low LDL, LDL/HDL ratio, TC/HDL ratio, log (TG/HDL), and apoB/apoA-I ratio. High glucose and TG were linked with an increased colon cancer risk, while high TC levels were associated with an increased rectal cancer risk.Conclusion. The persistent link between TC and rectal cancer risk as well as between TG and oesophageal and colon cancer risk in normoglycaemic individuals may imply their substantiality in gastrointestinal carcinogenesis.

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Adult BMI Change and Risk of Colon Cancer in Postmenopausal Women

Journal of Obesity ◽

10.1155/2012/857510 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Lyla Blake-Gumbs ◽

Zhengyi Chen ◽

Cheryl L. Thompson ◽

Nathan A. Berger ◽

Thomas C. Tucker ◽

...

Keyword(s):

Colon Cancer ◽

Weight Gain ◽

Cancer Risk ◽

Postmenopausal Women ◽

Early Adulthood ◽

Population Based ◽

Colon Cancer Risk ◽

Increased Risk ◽

Study Population ◽

Control Study

Purpose. We recently reported an association of adult BMI change with colon cancer risk. Here, we sought to further explore this association with respect to postmenopausal HRT use in a larger study population.Methods. We included 1,457 postmenopausal women participating in an ongoing population-based case-control study of colon cancer.Results. We confirmed a previously reported association of adulthood weight gain and increased risk of colon cancer: compared to those with <5 kg/m2change of BMI, women who reported moderate (5–10 kg/m2) and large (>10 kg/m2) BMI changes since their 20s had OR estimates of 1.54 (95% CI = 1.09–2.19) and 1.45 (95% CI = 0.90–2.33), respectively (Pfor trend = 0.05). Stratified analyses showed that this association was limited to HRT nonusers: ORs were 1.77 (95% CI = 1.02–3.05) and 2.21 (95% CI = 1.09–4.45), respectively (Pfor trend = 0.03), for BMI changes occurring between the 20s decade and time of recruitment among non-users. Similar associations were observed for BMI changes since the 30s decade. There was no association among HRT users.Conclusion. Our results suggest early adulthood weight gain increases colon cancer risk in postmenopausal women who do not use HRT.

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Antibiotic exposure is associated with an increased risk of cancer: a systematic review and meta-analysis

10.21203/rs.2.14633/v1 ◽

2019 ◽

Author(s):

Yuting Li ◽

Kaiyin He ◽

Xiaojuan Peng ◽

Chenxing Zhang ◽

Lu Zhong ◽

...

Keyword(s):

Cancer Risk ◽

Meta Analysis ◽

Antibiotic Use ◽

Epidemiological Studies ◽

Antibiotic Exposure ◽

Time Restrictions ◽

Common Cancer ◽

Increased Risk ◽

Cancer Types ◽

Risk Of Cancer

Abstract Background Several epidemiological studies have assessed the association between the use of antibiotics and cancer risk, but the results were inconsistent. Objective The objective of this study was to perform a meta-analysis to further evaluate possible association between antibiotic exposure and the risk of cancer. Methods We searched PubMed,Embase,Web of Science,and Chinese databases for studies on the association between antibiotic use and cancer without time restrictions. The risk estimates (hazard ratio (HR) or relative risk (RR) or Odds ratio (OR)) with their corresponding 95% confidence interval (CI) were calculated. Results A total of 23 observational studies with 19 case-control and 4 cohort studies were included in the meta-analysis. Exposure to antibiotics significantly increased the risk of cancer with an OR of 1.20 (95%CI 1.13-1.27, P=0.000). Subgroup meta-analysis by gender showed that the effect of antibiotic use on cancer risk was greater in male (34%) compared with that in female (19%). On the other hand, the risk of cancer increased with an increasing number of antibiotic prescriptions and the increasing cumulative days of antibiotic exposure. Moreover, of the 7 antibiotic types included, the six classes of antibiotics (penicillin, macrolides, quinolones, sulfonamides, tetracycline, cephalosporins) were associated with the increased risk of cancer. Further, of the 16 separate cancers included, exposure to antibiotics increased the risk of eight common cancer types (liver cancer, colorectal cancer, stomach and small intestine cancer, lymphomas, breast cancer, lung cancer, prostate cancer, and renal and bladder). Conclusions Exposure to common antibiotic types may increase the risk of the eight common cancer types in the studies population, especially in male, and the cancer risk increases with increasing antibiotic exposure intensity.

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