Common genetic variation in the APOE gene and risk of cancer: a systematic review and meta-analysis.

Substantial effort is now under way to identify and follow up patients who have received a computed tomography (CT) scan, to determine whether any increased risk of cancer resulting from exposure to ionising radiation during a scan can be detected. CT scans are becoming an increasingly popular and effective diagnostic tool, and their usage has risen dramatically in economically developed countries (UNSCEAR 2010). Each CT scan delivers an effective dose of between several mSv and a few tens of mSv, depending on the type of scan (UNSCEAR 2010). The radiation risk models that have been developed from the epidemiological study of groups receiving moderate and high doses (such as the Japanese survivors of the atomic-bombings of Hiroshima and Nagasaki) imply that the excess risk of cancer resulting from the low doses received during a CT scan is small, so that large and carefully designed and conducted studies are necessary to discern this predicted small additional risk. Such studies are important because of the direct evidence that they can potentially provide on the levels of risk resulting from low doses of radiation. The findings of large studies of patients who have experienced a CT scan at a young age are starting to become available—studies of infants, children and adolescents are a sensible starting point because the risk of radiation-induced cancer is generally greater at younger ages at exposure (UNSCEAR 2013).

OBJECTIVE: To investigate the risk of cancer associated with exposure to air pollution among bus drivers and tramway employees. METHODS: A retrospective cohort study of 18,174 bus drivers or tramway...

Angiotensin-Converting Enzyme Inhibitors and Risk of Esophageal and Gastric Cancer: A Nested Case-Control Study

Cholesterol and Cancer: Answers and New Questions

Duodeno-gastro-esophageal reflux of bile might cause laryngeal and pharyngeal cancer, but more research is required. Since cholecystectomy is followed by an increased risk such reflux, the risk of developing laryngeal or pharyngeal cancer after cholecystectomy was addressed. A population-based cohort study was conducted in Sweden during the period 1965-2008. The number of laryngeal or pharyngeal cancer cases observed in a large cohort of cholecystectomized patients was compared with the expected number, calculated from the entire Swedish population of corresponding age, gender and calendar year. Risk of laryngeal or pharyngeal cancer was calculated as standardized incidence ratio (SIR) with 95% confidence interval (CI). The cholecystectomy cohort included 345,251 patients who were followed up for 1-43 years and contributed 4,854,969 person-years at risk. The 192 new cases of laryngeal cancer and the 175 cases of pharyngeal cancer were not greater than the expected, providing SIR 0.99 (95% CI 0.85-1.14) and SIR 1.06 (95% CI 0.91-1.23), respectively. A longer latency period after cholecystectomy was not associated with any increased risk of any of these tumors. No differences between age groups or sexes were detected. Analyses restricted to verified squamous-cell carcinomas revealed similar results. In conclusion, cholecystectomy does not appear to be followed by any increased risk of laryngeal or pharyngeal cancer.

Incidence of stomach cancer has been declining in South Korea, but it still remains as the highest among men in the country. Cancers of upper and lower parts of stomach, and diffuse and intestinal type of stomach are thought to have different risk factors. Smoking, alcohol, and salty food intake are consistently associated with the risk of stomach cancer, but possible differential associations by topographic location and histological type are not well established. We evaluated the associations between smoking, alcohol, and salty food intake and the risk of cancers in upper (cardia and fundus), middle (body), and lower parts (antrum) of stomach, and of diffuse and intestinal type of stomach cancer in a prospective cohort study in Korea. Seoul Male Cohort was established in 1993. Members were recruited from the male beneficiaries of the Korean Health Insurance Company, who were aged 40-59 and living in Seoul. A lifestyle questionnaire survey was conducted through mailing. Dietary intake was measured using a quantitative food frequency questionnaire with 88 food items. Cancer occurrence was identified through data linkage to the Korean Central Cancer Registry and Korean Death Records. A total of 14,533 members were followed up until December 31, 2008, and 362 incident stomach cancer cases were identified. Multivariable hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated using Cox's regression model. None of the smoking, alcohol, and salty food intake was associated with risk of upper stomach cancer. Smoking had strongest association with risk of mid stomach cancer. Men who smoked currently and who stopped smoking for less than 4 years had 2.57 and 3.28 times higher risk of mid stomach cancer than never smokers (95% CI = 1.26-5.26, 1.36-7.96, respectively, ptrend=0.0036). Ex-smokers who stopped smoking for 4 or more years had no increase in risk of mid stomach cancer. Alcohol also had strongest association with risk of mid stomach cancer. The aHR of mid stomach cancer for those who had alcohol more than 45g/day compared to non-drinkers was 2.13 (95% CI = 0.94-4.82, ptrend=0.0353). Salty food and sodium intake had strongest association with risk of lower stomach cancer (Highest vs. lowest quartile, aHR=1.53 (95%CI = 0.93-2.52, ptrend=0.0670) for salty food, aHR=2.25 (95%CI = 1.18- 4.31, ptrend=0.0442) for sodium). Current smoking was strongly associated with both diffuse (aHR=2.44) and intestinal type of stomach cancer (aHR=1.87). Ex-smoking, alcohol, and salty food intake had significant positive association with intestinal type of stomach cancer, but not with diffuse type. In conclusion, smoking, alcohol, and salty food intake were mostly associated with risk of mid and lower stomach cancer and intestinal type of stomach cancer. Citation Format: Myung-Hee Shin, Seon-Mi Hwang, Min-Gew Choi, Duk-Hwan Kim, Jong-Myon Bae, Moo-Song Lee, Dong-Hyun Kim, Zhong-Min Li, Yoon-Ok Ahn. Association between smoking, alcohol, and salty food intake and risk of stomach cancer by topographic location and histological type in Seoul Male Cohort. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1273. doi:10.1158/1538-7445.AM2014-1273

Methionine Intake and Pancreatic Cancer Risk: Digesting the Evidence

Background:Per- and polyfluoroalkyl substances (PFAS) emissions from a plastic coating industrial source in southern New Hampshire (NH) have contaminated at least 65 square miles of drinking water. Prior research indicates that high levels of PFAS are associated with a variety of adverse health outcomes, including an increased risk of cancer. Reports indicate that mean blood serum levels of perfluorooctanoic acid (PFOA), one type of PFAS, in residents of the exposed community are more than 2 times greater than the mean blood serum level in the US. Merrimack public water supply customers also have higher average blood levels of perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) than the time—matched US average. A 2018 report concludes that the incidence rate of cancer in Merrimack does not exceed the incidence rate of cancer in NH in general. However, prior reporting on the risk of cancer in Merrimack is compared only to a state-wide metric influenced by the Merrimack cancer incidence.Methods:Our ecological study compared the risk in Merrimack, NH residents for 24 types of cancer between 2005 and 2014, targeted in a previous study, and all-cause cancers, to US national cancer rates and cancer rates in demographically similar towns in New England. Four New England “unexposed towns” were chosen based on demographic similarity to Merrimack, with no documented PFAS exposure in water supplies. We utilized unadjusted logistical regression to approximate risk ratios (RR) and 95% confidence intervals (CI) assessing the risk of cancer in Merrimack NH to each of the 4 comparator communities, the pooled comparator variable, and national average incidence.Results:Residents of Merrimack, NH experienced a significantly higher risk of thyroid cancer (RR = 1.47, 95% CI 1.12-1.93), bladder cancer (RR = 1.45, 95% CI 1.17-1.81), esophageal cancer (RR = 1.71, 95% CI 1.1-2.65), and mesothelioma (RR = 2.41, 95% CI 1.09-5.34), compared to national averages. Our work also suggests that Merrimack residents experienced a significantly higher risk of all-cause cancer (RR = 1.34, 95% CI 1.25-1.43), thyroid cancer (RR = 1.69, 95% CI 1.19-2.39), colon cancer (RR = 1.27, 95% CI 1.02-1.57), and prostate cancer (RR = 1.36, 95% CI 1.15, 1.6) compared with similarly exposed New England communities. Our results indicate that residents of Merrimack may also have a significantly lower risk of some site-specific cancers compared to national averages, including lower risk of prostate cancer (RR = 0.57, 95% CI 0.5-0.66), female breast cancer (RR = 0.60, 95% CI 0.52-0.68), ovarian cancer (RR = 0.52, 95% CI 0.33-0.84) and cervical cancer (RR = 0.29, 95% CI 0.12-0.69).Conclusion:Merrimack residents experienced a significantly higher risk of at least 4 types of cancer over 10 years between 2005 and 2014. Merrimack is a community with documented PFAS contamination of drinking water in public and private water sources. Results indicate that further research is warranted to elucidate if southern NH residents experience increased risk for various types of cancer due to exposure to PFAS contamination.

Background:Gastrectomy has been indicated as a risk factor for laryngeal cancer, and possibly also for pharyngeal cancer, but few studies are available. The postulated mechanism is increased bile reflux following gastrectomy.Methods:This was a population-based cohort study of patients who underwent gastrectomy for peptic ulcer disease between 1964 and 2008 in Sweden. Follow-up data for cancer was obtained from the Swedish Cancer Register. Relative risk was calculated as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs).Results:The gastrectomy cohort comprises 19 767 patients, contributing 348 231 person-years at risk. The observed number of patients with laryngeal (n=56) and pharyngeal cancer (n=28) was two-fold higher than the expected (SIR: 2.0, 95% CI: 1.5–2.6 and SIR: 2.4, 95% CI: 1.6–3.5, respectively). After exclusion of 5536 cohort members with tobacco- or alcohol-related disease, the point SIRs remained increased (SIR: 1.6, 95% CI: 1.1–2.2 and SIR: 1.7, 95% CI: 0.9–2.8, respectively). The SIRs of laryngeal and pharyngeal cancer increased with time after gastrectomy (P for trend <0.0001), and were particularly increased ⩾30 years after gastrectomy (SIR: 4.8, 95% CI: 2.1–9.5 and SIR: 10.2, 95% CI: 3.7–22.3, respectively).Conclusion:Gastrectomy for peptic ulcer disease might entail a long-term increased risk of laryngeal and pharyngeal cancer.

The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated. This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer. We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0. A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03). SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.

Previous observational studies have focused on the link between type 2 diabetes and the risk of cancer. However, the association between type 1 diabetes and the risk of cancer has not been well addressed. This study aimed to investigate the association between type 1 diabetes and the risk of cancer by using a meta-analysis of observational studies. We searched PubMed and EMBASE for observational studies that examined the association between type 1 diabetes and cancer in April 2017. We calculated the pooled odds ratios (ORs) or relative risks (RRs) with confidence intervals (CIs) from individual studies based on a random-effects model meta-analysis. We included a total of 15 observational studies with two case-control studies and 13 cohort studies involving 31 893 cancer patients among a total of 1 915 179 participants in the final analysis. In the random-effects meta-analysis of all studies, patients with type 1 diabetes had an increased risk of cancer (OR or RR, 1.29; 95% CI, 1.09-1.52; n = 15; I2 = 95.2%). In the subgroup meta-analysis by type of cancer, type 1 diabetes significantly increased the risk of cancers of stomach, lung, pancreas, liver, ovary and kidney, whereas it significantly decreased the risk of breast cancer (OR or RR, 0.91; 95% CI, 0.86-0.95; n = 9; I2 = 0%). This meta-analysis suggests that type 1 diabetes is associated with the increased risk of several types of cancer and the decreased risk of breast cancer. However, the plausible mechanisms for the decreased risk of breast cancer remain unclear. Further prospective studies with proper adjustment for possible confounding factors are warranted.

ObjectiveTo evaluate the effect of alcohol cessation on the risk of developing laryngeal and pharyngeal cancers, combining available evidence in the scientific literature in a meta-analysis.MethodsA systematic literature review was conducted, and a meta-analysis was applied on the retrieved studies. The generalised least squares method was used to estimate the trend from dose-response data to assess changes in the risks of laryngeal and pharyngeal cancers after drinking cessation.ResultsA total of 9 case-control studies were included in the meta-analysis (4 and 8 estimates for laryngeal and pharyngeal cancers, respectively). On average, alcohol drinking cessation was associated with a 2% yearly reduction in the risk of developing laryngeal and pharyngeal cancers. There was a considerable heterogeneity between the studies of pharyngeal cancer, but this was mostly due to two studies. The increased risk of laryngeal and pharyngeal cancers caused by alcohol was reversible; the time periods until the risks became equal to those of never drinkers were 36 (95% CI 11–106) and 39 (95% CI 13–103) years, respectively. Moreover, 5 years of drinking cessation was associated with a reduction of around 15% in the alcohol-related elevated risk of laryngeal and pharyngeal cancers.ConclusionAlthough a long time period is required to completely eliminate the alcohol-related elevated risk of laryngeal and pharyngeal cancers, a substantial risk reduction can be seen in the short term (5–10 years), and drinking cessation should therefore be encouraged to reduce the incidence of these cancers.

Issue Highlights

To study the asbestos-associated risk of lung cancer according to the histological type of cancer, the time of and time since diagnosis of asbestosis, the asbestos-associated risk for cancers other than lung cancer or mesothelioma, and the predictive value of asbestos-related pleural abnormalities as regards the risk of cancer. Finnish patients with asbestosis (n = 1,376) or asbestos-related benign pleural disease (n = 4,887) notified as an occupational disease since 1964 were followed-up through the Finnish Cancer Registry for cancer in 1967-95. Compared with the total cancer incidence in Finland, men with asbestosis had a raised risk of lung cancer (standardized incidence ratio [SIR] = 6.7; 95% confidence interval [CI] = 5.6-7.9), mesothelioma (SIR = 32, CI = 14-60) and cancer of the larynx (SIR = 4.2, CI = 1.4-9.8). The risk of lung cancer was similarly raised for all histological types of lung cancer (the highest in insulators) and did not change markedly over time of notification or duration of follow-up. Men with benign pleural disease had a raised risk of mesothelioma (SIR = 5.5, CI = 1.5-14) and a slightly elevated risk of lung cancer (SIR = 1.3, CI = 1.0-1.8). Among women with asbestosis, significant excess was found for lung cancer and mesothelioma. Asbestosis and asbestos-related benign pleural disease seem to possess different predictive values as regards the risk of lung cancer.

BackgroundAdiposity is a known risk factor for certain cancers; however, it is not clear whether the risk of cancer differs between individuals with high adiposity but different metabolic health status. The aim of this systematic literature review and meta-analysis of cohort studies was to evaluate associations between metabolic obesity phenotypes and overall and site-specific cancer risk.MethodsPubMed and Embase databases were used to identify relevant cohort studies up to the 6th of June 2023. Random-effects models were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for the association between metabolic obesity phenotypes and cancer risk. Certainty of evidence was assessed using the Cochrane methods and the GRADE tool. This study is registered with PROSPERO, number CRD42024549511.ResultsA total of 15,556 records were screened, and 31 publications covering 15 unique cohort studies were included in this analysis. Of these studies, 22 were evaluated as being at low risk of bias and 9 at moderate risk of bias. Compared to metabolically healthy normal-weight individuals (MHNW), metabolically unhealthy overweight/obese (MUOW/OB) individuals had a higher risk of overall (SRR = 1.21, 95% CI = 1.02–1.44, n = 3 studies, high certainty) and obesity-related cancers (SRR = 1.42, 95% CI = 1.15–1.74, n = 3, very low certainty). Specifically, MUOW/OB individuals were at higher risk of cancers of the postmenopausal breast (SRR = 1.32, 95% CI = 1.17–1.48, n = 7, low certainty), colorectum (SRR = 1.24, 95% CI = 1.16–1.31, n = 6, moderate certainty), endometrium (SRR = 2.31, 95% CI = 2.08–2.57, n = 4, high certainty), thyroid (SRR = 1.42, 95% CI = 1.29–1.57, n = 4, moderate certainty), kidney (SRR = 1.71, 95% CI = 1.40–2.10, n = 3, low certainty), pancreas (SRR = 1.35, 95% CI = 1.24–1.47, n = 3, high certainty), liver (SRR = 1.81, 95% CI = 1.36–2.42, n = 2, moderate certainty), gallbladder (SRR = 1.42, 95% CI = 1.17–1.73, n = 2, high certainty), bladder (SRR = 1.36, 95% CI = 1.19–1.56, n = 2, moderate certainty), and stomach (SRR = 1.50, 95% CI = 1.12–2.01, n = 2, high certainty). In addition, we found elevated risks of most of these cancers among individuals classified as MUNW and MHOW/OB phenotypes compared to those with MHNW phenotype. Our stratified analyses according to metabolic obesity phenotypes suggested that the elevated risks of some cancers were stronger in individuals with MUOW/OB versus those with MHOW/OB or MUNW phenotypes.ConclusionThese findings suggest that both higher adiposity and metabolic dysfunction were independently associated with increased risk of several cancers, with the strongest associations generally observed among those with both metabolic dysfunction and obesity.