Ching-Huan Wang

Background:Gynecologic cancers, including cervical, endometrial, and ovarian cancers, remain a major global health burden. Although histamine-2 receptor antagonists (H2RA) are inexpensive and widely accessible agents with reported anticancer properties, their associations with gynecologic cancer risk remain unclear. This study evaluated the potential of H2RAs for repurposing in chemoprevention.Methods:A nationwide, population-based case–control study was conducted using Taiwan’s National Health Insurance claims and Cancer Registry data from 2002 to 2016. A total of 97,736 women with newly diagnosed gynecologic cancer were matched 1:4 with controls by sex, age (±5 years), and month and year of diagnosis. H2RA exposure was defined as >60 days of use within two years before the index date. Adjusted odds ratios (aOR) and 95% confidence intervals were estimated using conditional logistic regression, adjusting for age, Charlson comorbidity index, and use of metformin, aspirin, and statins.Results:H2RA use was associated with reduced risks of cervical (aOR 0.80), endometrial (0.68), and ovarian cancers (0.78). Age-stratified analyses showed lower risks of cervical and endometrial cancers across all age groups, whereas the reduced ovarian cancer risk was most evident in women aged 40 to 64. Individual H2RA agents showed protective effects in the overall population, with cimetidine demonstrating the broadest reduction.Conclusions:Long-term H2RA use was associated with lower risks of major gynecologic cancers, with notable age- and agent-specific differences. Prospective studies are warranted to confirm causality and inform clinical application.Impact:Findings support repurposing H2RAs as accessible chemopreventive candidates for further translational application in women.

Distribution of case and control numbers stratified by H2RA agent, age group, and cancer subtype corresponding to Table 4.

Background: Gynecologic cancers, including cervical, endometrial, and ovarian cancers, remain a major global health burden. Although histamine-2 receptor antagonists (H2RA) are inexpensive and widely accessible agents with reported anticancer properties, their associations with gynecologic cancer risk remain unclear. This study evaluated the potential of H2RAs for repurposing in chemoprevention. Methods: A nationwide, population-based case–control study was conducted using Taiwan’s National Health Insurance claims and Cancer Registry data from 2002 to 2016. A total of 97,736 women with newly diagnosed gynecologic cancer were matched 1:4 with controls by sex, age (±5 years), and month and year of diagnosis. H2RA exposure was defined as >60 days of use within two years before the index date. Adjusted odds ratios (aOR) and 95% confidence intervals were estimated using conditional logistic regression, adjusting for age, Charlson comorbidity index, and use of metformin, aspirin, and statins. Results: H2RA use was associated with reduced risks of cervical (aOR 0.80), endometrial (0.68), and ovarian cancers (0.78). Age-stratified analyses showed lower risks of cervical and endometrial cancers across all age groups, whereas the reduced ovarian cancer risk was most evident in women aged 40 to 64. Individual H2RA agents showed protective effects in the overall population, with cimetidine demonstrating the broadest reduction. Conclusions: Long-term H2RA use was associated with lower risks of major gynecologic cancers, with notable age- and agent-specific differences. Prospective studies are warranted to confirm causality and inform clinical application. Impact: Findings support repurposing H2RAs as accessible chemopreventive candidates for further translational application in women.

Background: While the potential anti-cancer effects of antidepressants have been investigated, limited research has been conducted incorporating age-specific analyses for individual tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). This study aims to elucidate the associations between TCAs and SSRIs with gynecologic cancers and to identify specific age groups and cancer types that may benefit from the chemopreventive effects of these medications. Methods: A case-control study comprised 97,736 female patients diagnosed with gynecologic cancers between 2002 and 2016. Each newly diagnosed case of cervical, ovarian, or uterine cancer was matched with four controls. Both cases and controls were then stratified by age to perform subgroup analyses. Associations between antidepressant use and cancer risk were evaluated using multivariable conditional logistic regression models. Results: The TCA class was significantly associated with reduced risks of cervical, ovarian, and uterine cancers, displaying adjusted odds ratios (aORs) of 0.799, 0.775, and 0.813, respectively. The SSRI class also indicated reduced risks, with aORs of 0.736, 0.638, and 0.567 for the same cancer types. Particularly noteworthy were females aged 40–64, who demonstrated the most significant associations between gynecologic cancers and using TCAs or SSRIs. Conclusions: TCAs and SSRIs are associated with reduced risks of developing cervical, ovarian, and uterine cancers. The middle-aged population may have the most significant potential for future research on drug repurposing against gynecologic cancers, and both cervical and uterine cancers are potential targets for drug repurposing involving TCAs or SSRIs.

Pancreatic cancer is among the deadliest cancers, with a grim prognosis despite advances in treatment. We conducted a population‐based case–control study from Taiwan, linking Health and Welfare Data Science Center data to the Taiwan Cancer Registry, which offers a promising strategy for its treatment through drug repurposing. The study aims to identify the association of anti‐parkinsonian drugs with pancreatic cancer risk across different age groups. The analysis encompassed 18,921 pancreatic cancer cases and 75,684 matched controls, employing conditional logistic regression to assess the impact of anti‐parkinsonian drugs on the risk of pancreatic cancer. Key findings revealed a statistically significant association of the administration with specific anti‐parkinsonian medications, including anticholinergic agents, tertiary amines, dopa derivatives, and dopamine receptor agonists, with a reduction in pancreatic cancer risk. These associations were represented as adjusted odds ratios (aORs), ranging from 0.620 (95% CI 0.470–0.810) to 0.764 (95% CI 0.655–0.891). Further, age‐stratified analysis revealed variations in efficacy across different age groups. Anticholinergic agents and tertiary amines exhibited greater effectiveness in the 40–64‐year age group (aOR, 0.653; 95% CI, 0.489–0.872), whereas dopa derivatives and dopamine receptor agonists were particularly efficacious in the cohort aged ≥65 years (aOR, 0.728; 95% CI, 0.624–0.850 and aOR, 0.665; 95% CI, 0.494–0.894, respectively). Notably, specific drugs such as trihexyphenidyl, levodopa/dopa decarboxylase inhibitor (DDCI), and pramipexole demonstrated a significant decrease in cancer risk, especially in the elderly population. These preliminary findings can contribute to the possible therapeutic role of anti‐parkinsonian drugs in the treatment of pancreatic cancer.

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan’s Health and Welfare Data Science Center (2000–2016) and linked with Taiwan Cancer Registry (1979–2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85–0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20–39 years (aOR: 0.70, 95% CI: 0.58–0.85), 40–64 years (aOR: 0.77, 95% CI: 0.74–0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83–0.91), and overall (aOR: 0.81, 95% CI: 0.79–0.84). Ovarian cancer risk was significantly lower in the groups aged 40–64 years (aOR: 0.76, 95% CI: 0.69–0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75–092), and overall (aOR: 0.79, 95% CI: 0.74–0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20–39 years (aOR: 2.54, 95% CI: 1.79–3.61), 40–64 years (aOR: 1.08, 95% CI: 1.02–1.14), and overall (aOR: 1.06, 95% CI: 1.01–1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40–64 years (aOR: 0.88, 95% CI: 0.84–0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83–0.90), and overall (aOR: 0.88, 95% CI: 0.85–0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86–0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality.

Background: Firm conclusions about whether long-term proton pump inhibitor (PPI) drug use impacts female cancer risk remain controversial. Objective: We aimed to investigate the associations between PPI use and female cancer risks. Methods: A nationwide population-based, nested case-control study was conducted within Taiwan’s Health and Welfare Data Science Center’s databases (2000–2016) and linked to pathologically confirmed cancer data from the Taiwan Cancer Registry (1979–2016). Individuals without any cancer diagnosis during the 17 years of the study served as controls. Case and control patients were matched 1:4 based on age, gender, and visit date. Conditional logistic regression with 95% confidence intervals (CIs) was applied to investigate the association between PPI exposure and female cancer risks by adjusting for potential confounders such as the Charlson comorbidity index and medication usage (metformin, aspirin, and statins). Results: A total of 233,173 female cancer cases were identified, consisting of 135,437 diagnosed with breast cancer, 64,382 with cervical cancer, 19,580 with endometrial cancer, and 13,774 with ovarian cancer. After matching each case with four controls, we included 932,692 control female patients. The number of controls for patients with breast cancer, cervical cancer, endometrial cancer, and ovarian cancer was 541,748, 257,528, 78,320, and 55,096, respectively. The use of PPIs was significantly associated with reduced risk of breast cancer and ovarian cancer in groups aged 20–39 years (adjusted odds ratio (aOR): 0.69, 95%CI: 0.56–0.84; p < 0.001 and aOR: 0.58, 95%CI: 0.34–0.99; p < 0.05, respectively) and 40–64 years (aOR: 0.89, 95%CI: 0.86–0.94; p < 0.0001 and aOR: 0.87, 95%CI: 0.75–0.99; p < 0.05, respectively). PPI exposure was associated with a significant decrease in cervical and endometrial cancer risks in the group aged 40–64 years (with aOR: 0.79, 95%CI: 0.73–0.86; p < 0.0001 and aOR: 0.72, 95%CI: 0.65–0.81; p < 0.0001, respectively). In contrast, in elderly women, PPI use was found to be insignificantly associated with female cancers among users. Conclusions: Our findings, based on real-world big data, can depict a comprehensive overview of PPI usage and female cancer risk. Further clinical studies are needed to elucidate the effects of PPIs on female cancers.

Despite previous studies on statins, aspirin, metformin, and angiotensin-converting-enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), little has been studied about all their possible combinations for chemoprevention against cancers. This study aimed to comprehensively analyze the composite chemopreventive effects of all the combinations. In this case-control study, health records were retrieved from claims databases of Taiwan’s Health and Welfare Data Science Center. Eligible cases were matched at a 1:4 ratio with controls for age and sex. Both cases and controls were categorized into 16 exposure groups based on medication use. A total of 601,733 cancer cases were identified. Cancer risks (denoted by adjusted odds ratio; 99% confidence interval) were found to be significantly decreased: overall risk of all cancers in statin-alone (0.864; 0.843, 0.886), aspirin-alone (0.949; 0.939, 0.958), and ACEIs/ARBs (0.982; 0.978, 0.985) users; prostate (0.924; 0.889, 0.962) and female breast (0.967; 0.936, 1.000) cancers in metformin-alone users; gastrointestinal, lung, and liver cancers in aspirin and/or ACEIs/ARBs users; and liver cancer (0.433; 0.398, 0.471) in statin users. In conclusion, the results found no synergistic effect of multiple use of these agents on cancer prevention. Use of two (statins and aspirin, statins and metformin, statins and ACEIs/ARBs, and aspirin and ACEIS/ARBs) showed chemopreventive effects in some combinations, while the use of four, in general, did not.

Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case‐control study was conducted using Taiwan’s Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ≥20 years and had a first‐time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46‐1.54; P < .0001) compared with non–users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48‐2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17‐1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01‐1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15‐1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients’ condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms.

Background: Existing epidemiological evidence regarding the association between the long-term use of drugs and cancer risk remains controversial. Objective: We aimed to have a comprehensive view of the cancer risk of the long-term use of drugs. Methods: A nationwide population-based, nested, case-control study was conducted within the National Health Insurance Research Database sample cohort of 1999 to 2013 in Taiwan. We identified cases in adults aged 20 years and older who were receiving treatment for at least two months before the index date. We randomly selected control patients from the patients without a cancer diagnosis during the 15 years (1999-2013) of the study period. Case and control patients were matched 1:4 based on age, sex, and visit date. Conditional logistic regression was used to estimate the association between drug exposure and cancer risk by adjusting potential confounders such as drugs and comorbidities. Results: There were 79,245 cancer cases and 316,980 matched controls included in this study. Of the 45,368 associations, there were 2419, 1302, 662, and 366 associations found statistically significant at a level of P<.05, P<.01, P<.001, and P<.0001, respectively. Benzodiazepine derivatives were associated with an increased risk of brain cancer (adjusted odds ratio [AOR] 1.379, 95% CI 1.138-1.670; P=.001). Statins were associated with a reduced risk of liver cancer (AOR 0.470, 95% CI 0.426-0.517; P<.0001) and gastric cancer (AOR 0.781, 95% CI 0.678-0.900; P<.001). Our web-based system, which collected comprehensive data of associations, contained 2 domains: (1) the drug and cancer association page and (2) the overview page. Conclusions: Our web-based system provides an overview of comprehensive quantified data of drug-cancer associations. With all the quantified data visualized, the system is expected to facilitate further research on cancer risk and prevention, potentially serving as a stepping-stone to consulting and exploring associations between the long-term use of drugs and cancer risk.