Aspirin but not statins is inversely related to gastric cancer with a duration-risk effect: Results from the Stomach Cancer Pooling Project Consortium.

BACKGROUND: Aspirin and statins have been suggested to have potential chemopreventive effects against gastric cancer (GC), although the results of previous studies have been inconsistent. This study therefore aimed to investigate the association between the use of aspirin and statins and GC. METHODS: A pooled analysis of seven case-control studies within the Stomach Cancer Pooling Project, including 3220 cases and 9752 controls, was conducted. Two-stage modeling analyses were used to estimate the association between aspirin and statin use and GC after adjusting for potential confounders. RESULTS: The pooled odds ratio (OR) of GC for aspirin users versus nonusers was 0.72 (95% confidence interval [CI], 0.54-0.95). The protective effect of aspirin appeared stronger in individuals without a GC family history (OR, 0.60; 95% CI, 0.37-0.95), albeit with borderline heterogeneity between those with and without a family history (p = .064). The OR of GC decreased with increasing duration of aspirin use, with an OR of 0.41 (95% CI, 0.18-0.95) for durations of ≥15 years. An inverse, nonsignificant association with the risk of GC was observed for the use of statins alone (OR, 0.79; 95% CI, 0.52-1.18). CONCLUSIONS: These findings suggest that aspirin use, particularly long-term use, is associated with a reduced risk of GC, whereas a similar association was not observed with statins, possibly because of the low frequency of use.

The contribution of second primary cancers to the mortality of patients with a first primary breast cancer.

PURPOSE: Second primary cancers (SPCs) are estimated to affect nearly 5% of patients with breast cancer within 10 years of their diagnosis. This study aimed to estimate the contribution of SPCs to the mortality of patients with a breast first primary cancer (FPC). METHODS: A population-based cohort of 17,210 patients with a breast FPC diagnosed between 2000 and 2010 was followed for SPCs (31/12/2015) and vital status (30/06/2021). Patients diagnosed with an SPC (265 synchronous and 897 metachronous, ≤ 1 and > 1 year after the FPC, respectively) were matched (1:3, by five-year age group and year of breast FPC diagnosis) to those without an SPC and alive when the corresponding SPC was diagnosed. RESULTS: Significantly higher hazards of death were found among patients with an SPC [hazard ratio of 1.56, 95% confidence interval (CI) 1.29-1.89 for synchronous SPCs; and 2.85, 95%CI 2.56-3.17 for metachronous SPCs] compared to patients with a breast FPC only. Estimates were higher for synchronous lung, stomach, non-Hodgkin lymphoma and breast SPCs, and metachronous liver, stomach, ovary, lung, rectum, corpus uteri, colon, breast, and non-Hodgkin lymphoma SPCs. The 15-year cumulative mortality was 59.5% for synchronous SPCs and 68.7% for metachronous SPCs, which was higher than in patients with a breast FPC only (43.6% and 44.8%, respectively). CONCLUSIONS: In Northern Portugal, patients with an SPC following a breast FPC have a higher mortality compared with patients with a breast FPC only.

The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 µg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85-1.56), and the OR100 µg/day = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Dietary intake of copper and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Evidence on the potential association between dietary copper intake and gastric cancer (GC) is lacking. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project-an international consortium of epidemiological studies on GC. METHODS: Data from five case-control studies within the StoP Project were included (2448 cases, 4350 controls). We estimated adjusted odds ratios (ORs) and 95% CIs for the association between dietary copper intake and GC using multivariable mixed-effects logistic regression models. We also modelled the dose-response relationship between copper intake and GC using a logistic mixed-effects model with fractional polynomial. RESULTS: The OR for the highest quartile of copper intake compared with the lowest one was 0.78 (95% CI: 0.63-0.95; P for trend = 0.013). Results were similar for non-cardia-type (OR: 0.72; 95% CI: 0.57-0.91), intestinal-type (OR: 0.75; 95% CI: 0.56-0.99) and other histological-type GC (OR: 0.65; 95% CI: 0.44-0.96). The dose-response analysis showed a steep decrease in ORs for modest intakes (<1 mg/day), which were subsequently steady for ≤3 mg/day (OR: 0.09; 95% CI: 0.02-0.41) and slowly increased for higher intakes. CONCLUSIONS: The findings of our large study suggest that copper intake might be inversely associated with GC, although their confirmation by prospective studies is required.

Empirical sample-specific approaches to define HPV16 and HPV18 seropositivity in unvaccinated, young, sexually active women.

Given low seroconversion rates following human papillomavirus (HPV) infection, fixed external cutoffs may lead to errors in estimating HPV seroprevalence. We evaluated finite mixture modeling (FMM) and group-based trajectory modeling (GBTM) among unvaccinated, sexually active, HPV-exposed women to determine study-specific HPV16 and HPV18 seropositivity thresholds. We included 399 women (aged 18-24 years) enrolled in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study between 2005 and 2011 in Montreal, Canada. Participants' blood samples from up to six visits spanning 2 years were tested by multiplex serology for antibodies [median fluorescence intensity (MFI)] specific to bacterially expressed HPV16 and HPV18 L1 glutathione S-transferase fusion proteins. We applied FMM and GBTM to baseline and longitudinal antibody titer measurements, respectively, to define HPV type-specific seronegative and seropositive distributions. Study-specific thresholds were generated as five standard deviations above the mean seronegative antibody titers, mimicking cutoffs (HPV16: 422 MFI; HPV18: 394 MFI) derived from an external population of sexually inactive, HPV DNA-negative Korean women (aged 15-29 years). Agreement (kappa) of study-specific thresholds was evaluated against external cutoffs. Seroprevalence estimates using FMM (HPV16: 27.5%-43.2%; HPV18: 21.7%-49.5%) and GBTM (HPV16: 11.8%-11.8%; HPV18: 9.9%-13.4%) thresholds exceeded those of external cutoffs (HPV: 10.2%; HPV18: 9.7%). FMM thresholds showed slight-to-moderate agreement with external cutoffs (HPV16: 0.26%-0.46%; HPV18: 0.20%-0.56%), while GBTM thresholds exhibited high agreement (HPV16: 0.92%-0.92%; HPV18: 0.82%-0.99%). Kappa values suggest that GBTM, used for longitudinal serological data, and otherwise FMM, for cross-sectional data, are robust methods for determining the HPV serostatus without prior classification rules.IMPORTANCEWhile human papillomavirus (HPV) seropositivity has been employed as an epidemiologic determinant of the natural history of genital HPV infections, only a fraction of women incidentally infected with HPV respond by developing significant antibody levels. HPV seropositivity is often determined by a dichotomous fixed cutoff based on the seroreactivity of an external population of women presumed as seronegative, given the lack of evidence of HPV exposure. However, considering the variable nature of seroreactivity upon HPV infection, which arguably varies across populations, such externally defined cutoffs may lack specificity to the population of interest, causing inappropriate assessment of HPV seroprevalence and related epidemiologic uses of that information. This study demonstrates that finite mixture modeling (FMM) and group-based trajectory modeling (GBTM) can be used to independently estimate seroprevalence or serve as the basis for defining study-specific seropositivity thresholds without requiring prior subjective assumptions, consequently providing a more apt internally valid discrimination of seropositive from seronegative individuals.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

Serologic response to human papillomavirus genotypes following vaccination: findings from the HITCH cohort study.

BACKGROUND: Human papillomavirus (HPV) infection contributes to approximately 5% of the worldwide cancer burden. The three-dose HPV vaccine has demonstrated immunogenicity and efficacy. Humoral responses may be critical for preventing, controlling, and/or eliminating HPV infection. Using data from the HITCH cohort, we analysed humoral immune response to HPV vaccination among women in relation to the phylogenetic relatedness of HPV genotypes. METHODS: We included 96 women aged 18-24 years attending college or university in Montreal, Canada. Participants provided blood samples at enrolment and five follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S-transferase fusion proteins of multiple Alphapapillomavirus types, and to virus-like particles (VLP-L1) of HPV16 and HPV18 were measured using multiplex serology. We assessed correlations between antibody seroreactivities using Pearson correlations (r). RESULTS: At enrolment, 87.7% of participants were unvaccinated, 2.4% had received one, 3.2% two, and 6.7% three doses of HPV vaccine. The corresponding L1 seropositivity to any HPV was 41.2%, 83.3%, 100%, and 97.0%. Between-type correlations for L1 seroreactivities increased with the number of vaccine doses, from one to three. Among the latter, the strongest correlations were observed for HPV58-HPV33 (Pearson correlation [r] = 0.96; α9-species); HPV11-HPV6 (r = 0.96; α10-species); HPV45-HPV18 (r = 0.95; α7-species), and HPV68-HPV59 (r = 0.95; α7-species). CONCLUSIONS: Correlations between HPV-specific antibody seroreactivities are affected by phylogenetic relatedness, with anti-L1 correlations becoming stronger with the number of vaccine doses received.

Association between sociodemographic and clinical features, health behaviors, and health literacy of patients with prostate cancer and prostate cancer prognostic stage.

Patient characteristics may influence access and acceptance of Prostate Specific Antigen test, and therefore, the timing of prostate cancer (PCa) diagnosis. A group of 361 patients from a cohort (n = 451) diagnosed with PCa in 2018-2020 at the Portuguese Institute of Oncology of Porto was evaluated before treatment, using a structured interview, the Medical Term Recognition Test, and the EORTC Quality of Life Questionnaire QLQ-PR25. PCa prognostic stages (I, II, III, IV) were attributed according to the American Joint Committee on Cancer eighth edition. Multinomial logistic regression was used to compute the odds ratio and 95% confidence interval (OR [95% CI]), considering PCa stage II, the most frequent, as reference. Older age (OR = 4.21 [2.24-7.93]), living outside the Porto Metropolitan Area while having low income (OR = 6.25 [1.53-25.62]), and erectile dysfunction (OR = 2.22 [0.99-4.99]) were associated with stage III, while urination during the night (OR = 3.02 [1.42-6.41]) was associated with stage IV. Urine leakage was less frequent in stage III (OR = 0.23 [0.08-0.68]), and living with a partner (OR = 0.41 [0.19-0.88]) and family history of cancer (OR = 0.25 [0.07-0.86]) in stage IV. Health literacy was not associated with PCa stage but lower education was less frequent in stage I (OR = 0.27 [0.11-0.69]). Patient sociodemographic and clinical characteristics should be considered as targets to improve PCa early detection and prognosis.

Second primary cancers among females with a first primary breast cancer: a population-based study in Northern Portugal.

PURPOSE: To estimate the incidence rate of second primary cancers (SPCs) and the cumulative incidence of metachronous [diagnosed > 2 months after a first primary cancer (FPC)] SPCs in patients with a breast FPC, and to compare the incidence of SPC [overall, synchronous (≤ 2 months of the FPC) and metachronous] with that expected in the general female population. METHODS: A cohort of patients with a breast FPC from the North Region Cancer Registry of Portugal, diagnosed in 2000-2010 (n = 15,981), was followed to 31 December 2015 for synchronous and metachronous SPCs. Cumulative incidence of metachronous SPCs considering death as a competing event, and incidence rates and standardized incidence ratios of SPCs were estimated. RESULTS: The diagnosis of an SPC occurred in 1229 (7.7%) of patients with a breast FPC. SPCs occurred mainly in the breast, followed by digestive organs, lung, thyroid, and female genital organs. Globally, patients with a breast FPC had a higher incidence for all types of cancer compared to the general female population, and in particular for cancers of the breast, stomach, colon, lung, lymphoma, uterus, and ovary. The 10-year cumulative incidence of metachronous SPCs following a breast FPC was 6.6% and the corresponding 10-year cumulative mortality was 26.2%. CONCLUSION: In Portugal, patients with a breast FPC have a higher incidence of cancer compared to the general female population, highlighting important aspects of care, surveillance, and counselling among this growing number of patients.

Cancer-Related Neuropathic Pain, Chemotherapy-Induced Peripheral Neuropathy and Cognitive Decline in a 5-Year Prospective Study of Patients with Breast Cancer-NEON-BC.

This study aims to estimate the prevalence and to identify the determinants of cancer-related neuropathic pain (CRNP), chemotherapy-induced peripheral neuropathy (CIPN) and cognitive decline among patients with breast cancer over five years after diagnosis. Women with an incident breast cancer (n = 462) and proposed for surgery were recruited at the Portuguese Institute of Oncology-Porto in 2012 and underwent systematic neurological examinations and evaluations with the Montreal Cognitive Assessment (MoCA) before treatment and after one, three, and five years. Multivariate logistic regression was used to assess the determinants of CRNP and CIPN, and multivariate linear regression for the variation in MoCA scores. Prevalence of CRNP and CIPN decreased from the first to the fifth year after diagnosis (CRNP: from 21.1% to 16.2%, p = 0.018; CIPN: from 22.0% to 16.0% among those undergoing chemotherapy, p = 0.007). Cognitive impairment was observed in at least one assessment in 17.7% of the women. Statistically significant associations were observed between: cancer stage III and both CRNP and CIPN; triple negative breast cancer, chemotherapy, axillary node dissection, older age, higher education, and being single and CRNP; taxanes and fruit and vegetable consumption and CIPN. Anxiety, depression and poor sleep quality at baseline were associated with decreases in MoCA values from pre- to post-treatment and with CRNP. Follow-up protocols should consider the persistence of CRNP, CIPN, and cognitive impairment for several years following diagnosis.

Cancers Attributable to Infections in the US in 2017: A Meta-Analysis.

Importance: Infections are largely modifiable causes of cancer. However, there remains untapped potential for preventing and treating carcinogenic infections in the US. Objective: To estimate the percentage and number of incident cancers attributable to infections in the US among adults and children for the most recent year cancer incidence data were available (2017). Data Sources: A literature search from 1946 onward was performed in MEDLINE on January 6, 2023, to obtain the data required to calculate population attributable fractions for 31 infection-cancer pairs. National Health and Nutrition Examination Survey data were used to estimate the population prevalence of hepatitis B and C viruses and Helicobacter pylori. Study Selection: Studies conducted in the US or other Western countries were selected according to specific infection-cancer criteria. Data Extraction and Synthesis: Data from 128 studies were meta-analyzed to obtain the magnitude of an infection-cancer association or prevalence of the infection within cancer cells. Main Outcomes and Measures: The proportion of cancer incidence attributable to 8 infections. Results: Of the 1 666 102 cancers diagnosed in 2017 among individuals aged 20 years or older in the US, 71 485 (4.3%; 95% CI, 3.1%-5.3%) were attributable to infections. Human papillomavirus (n = 38 230) was responsible for the most cancers, followed by H pylori (n = 10 624), hepatitis C virus (n = 9006), Epstein-Barr virus (n = 7581), hepatitis B virus (n = 2310), Merkel cell polyomavirus (n = 2000), Kaposi sarcoma-associated herpesvirus (n = 1075), and human T-cell lymphotropic virus type 1 (n = 659). Cancers with the most infection-attributable cases were cervical (human papillomavirus; n = 12 829), gastric (H pylori and Epstein-Barr virus; n = 12 565), oropharynx (human papillomavirus; n = 12 430), and hepatocellular carcinoma (hepatitis B and C viruses; n = 10 017). The burden of infection-attributable cancers as a proportion of total cancer incidence ranged from 9.6% (95% CI, 9.2%-10.0%) for women aged 20 to 34 years to 3.2% (95% CI, 2.4%-3.8%) for women aged 65 years or older and from 6.1% (95% CI, 5.2%-7.0%) for men aged 20 to 34 years to 3.3% (95% CI, 1.9%-4.4%) for men aged 65 years or older. Among those aged 19 years or younger, 2.2% (95% CI, 1.3%-3.0%) of cancers diagnosed in 2017 were attributable to Epstein-Barr virus. Conclusions and Relevance: Infections were estimated to be responsible for 4.3% of cancers diagnosed among adults in the US in 2017 and, therefore, represent an important target for cancer prevention efforts.

Differences in site-specific cancer incidence by individual- and area-level income in Canada from 2006 to 2015.

Income, a component of socioeconomic status, influences cancer risk as a social determinant of health. We evaluated the independent associations between individual- and area-level income and site-specific cancer incidence in Canada. We used data from the 2006 and 2011 Canadian Census Health and Environment Cohorts, which are probabilistically linked datasets constituted by 5.9 million and 6.5 million respondents of the 2006 Canadian long-form census and 2011 National Household Survey, respectively. Individuals were linked to the Canadian Cancer Registry through 2015. Individual-level income was derived using after-tax household income adjusted for household size. Annual tax return postal codes were used to assign area-level income quintiles to individuals for each year of follow-up. We calculated age-standardized incidence rates (ASIR) and rate ratios for cancers overall and by site. We conducted multivariable negative binomial regression to adjust these rates for other demographic and socioeconomic variables. Individuals of lower individual- and area-level income had higher ASIRs compared to those in the wealthiest income quintile for head and neck, oropharyngeal, esophageal, stomach, colorectal, anal, liver, pancreas, lung, cervical and kidney and renal pelvis cancers. Conversely, individuals of wealthier individual- and area-level income had higher ASIRs for melanoma, leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, breast, uterine, prostate and testicular cancers. Most differences in site-specific incidence by income quintile remained after adjustment. Although Canada's publicly funded healthcare system provides universal coverage, inequalities in cancer incidence persist across individual- and area-level income gradients. Our estimates suggest that individual- and area-level income affect cancer incidence through independent mechanisms.

Long-term neurological complications in COVID-19 survivors: study protocol of a prospective cohort study (NeurodegCoV-19).

BACKGROUND: Evidence suggests an association between SARS-CoV-2 infection and worse performance on cognitive tests, and a higher risk of Parkinson's disease (PD) and dementia up to 6 and 12 months after infection, respectively. Longer follow-ups with comparison groups are needed to clarify the potentially increased risk of neurodegenerative diseases in COVID-19 survivors, namely those infected before mass vaccination. METHODS: A prospective study started in July 2022 with four cohorts of 150 individuals each, defined according to SARS-CoV-2 infection and hospitalisation status between March 2020 and February 2021: cohort 1-hospitalised due to SARS-CoV-2 infection; cohort 2-hospitalised, COVID-19-free; cohort 3-infected, not hospitalised; cohort 4-not infected, not hospitalised. Cohort 2 will be matched to cohort 1 according to age, sex, level of hospitalisation care and length of stay; cohort 4 will be age-matched and sex-matched to cohort 3. Baseline, 1-year and 2-year follow-up evaluations will include: cognitive performance assessed with the Montreal Cognitive Assessment (MoCA) and neuropsychological tests; the assessment of prodromal markers of PD with Rapid Eye Movement Sleep Behaviour Disorder single-question Screen and self-reported olfactory and gustative alterations; screening of PD with the 9-item PD screening questionnaire; gait evaluation with Timed Up&Go test. Suspected cases of cognitive impairment and PD will undergo a clinical evaluation by a neurologist. Frequency measures of neurological complications, prodromal markers and diagnoses of dementia and PD, will be presented. The occurrence of cognitive decline-the difference between baseline and 1-year MoCA scores 1.5 SD below the mean of the distribution of the variation-will be compared between cohorts 1 and 2, and cohorts 3 and 4 with OR estimated using multivariate logistic regression. ETHICS AND DISSEMINATION: This study received ethics approval from the Ethics Committees of the health units Unidade Local de Saúde de Matosinhos and Centro Hospitalar de Entre Douro e Vouga, and informed consent is signed for participating. Results will be disseminated among the scientific community and the public.

Intake of Proton-Pump Inhibitors and Gastric Cancer within the Stomach Cancer Pooling (StoP) Project.

BACKGROUND: A potential association between proton-pump inhibitors (PPI) and gastric cancer remains undefined. Thus, we aimed to evaluate such association within the Stomach cancer Pooling (StoP) Project. METHODS: Data from five case-control studies of the StoP Project were included (1,889 cases and 6,517 controls). We assessed the impact of different exposure definitions, specifically any reported use of PPIs and exposure definitions based on the duration of PPI intake. Additionally, we modeled the dose-response relationship between the cumulative duration of PPI intake and gastric cancer. RESULTS: Significant associations between PPI intake and gastric cancer, both overall and in the stratified analyses, were limited to exposure definitions based on short durations of intake. The overall odds ratio (OR) for any reported PPI intake was 1.78 [95% confidence interval (CI): 0.76-4.14]. In the dose-response analysis, the ORs of gastric cancer were found to be higher for short durations of PPI intake (6 months: OR 3.26; 95% CI: 2.40-4.42; one year: OR 2.14; 95% CI: 1.69-2.70; 2 years: OR 1.50; 95% CI: 1.22-1.85; 3 years: OR 1.27; 95% CI: 1.03-1.56), with the association becoming not significant for durations longer than 3 years. CONCLUSIONS: Our findings suggest that the observed association between PPIs and gastric cancer might be mainly due to reverse causality. IMPACT: The results of this study suggest that PPIs are a safe therapeutic choice regarding their effect on the occurrence of gastric cancer. See related commentary by Richman and Leiman, p. 1127.

Yoghurt Intake and Gastric Cancer: A Pooled Analysis of 16 Studies of the StoP Consortium.

BACKGROUND: Yoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC). METHODS: We pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted. RESULTS: The analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94-1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88-0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85-0.99) and 0.78 (95% CI = 0.73-0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91-1.02) for cardia, 1.03 (95% CI = 1.00-1.07) for non-cardia, 1.12 (95% CI = 1.07-1.19) for diffuse and 1.02 (95% CI = 0.97-1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women. CONCLUSIONS: We found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association.

Site-Specific Cancer Incidence by Race and Immigration Status in Canada 2006-2015: A Population-Based Data Linkage Study.

BACKGROUND: The Canadian Cancer Registry (CCR) does not collect demographic data beyond age and sex, making it difficult to monitor health inequalities. Using data linkage, we compared site-specific cancer incidence rates by race. METHODS: The 2006 and 2011 Canadian Census Health and Environment Cohorts are population-based probabilistically linked datasets of 5.9 million respondents of the 2006 long-form census and 6.5 million respondents of the 2011 National Household Survey. Race was self-reported. Respondent data were linked with the CCR up to 2015. We calculated age-standardized incidence rate ratios (ASIRR), comparing group-specific rates to the overall population rate with bootstrapped 95% confidence intervals (CI). We used negative binomial regressions to adjust for socioeconomic variables and assess interactions with immigration status. RESULTS: The age-standardized overall cancer incidence rate was lower in almost all non-White racial groups than in the overall population, except for White and Indigenous peoples who had higher incidence rates than the overall population (ASIRRs, 1.03-1.04). Immigrants had substantially lower age-standardized overall cancer incidence rates than nonimmigrants (ASIRR, 0.83; 95% CI, 0.82-0.84). Stomach, liver, and thyroid cancers and multiple myelomas were the sites where non-White racial groups had consistently higher site-specific cancer incidence rates than the overall population. Immigration status was an important modifier of cancer risk in the interaction model. CONCLUSIONS: Differences in cancer incidence between racial groups are likely influenced by differences in lifestyles, early life exposures, and selection factors for immigration. IMPACT: Data linkage can help monitor health inequalities and assess progress in preventive interventions against cancer. See related commentary by Withrow and Gomez, p. 876.

Serologic Response to Human Papillomavirus Genotypes Among Unvaccinated Women: Findings From the HITCH Cohort Study.

BACKGROUND: Humoral immune responses may be critical for preventing, controlling, and/or eliminating human papillomavirus (HPV) infection. We analyzed humoral response to natural HPV infection considering phylogenetic relatedness among unvaccinated women. METHODS: We included 399 young women attending university/college in Montreal, Canada who were participants of the HITCH cohort. Participants provided blood samples at baseline and 5 follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S-transferase (GST) fusion proteins, and virus-like particles (VLP-L1) of Alphapapillomavirus types were measured using multiplex serology. We assessed correlations and associations between HPV types at baseline using Pearson correlation coefficients (r) and univariable linear regressions. RESULTS: At baseline, > 40% were seropositive for GST-L1 antibodies of at least 1 HPV type. Strong correlations between GST-L1 were observed for α9 HPV types: 58-52 (r = 0.86), 58-33 (r = 0.75), 33-52 (r = 0.72), and between GST-E6: 52-11 (r = 0.84), 52-18 (r = 0.79), 58-33 (r = 0.78), 35-11 (r = 0.76). HPV16 VLP-L1 moderately explained variability in HPV16 GST-L1 (regression coefficient [b] = 0.38, R2 = 43.1%), and HPV45 GST-L1 in HPV18 GST-L1 (b = 0.68, R2 = 42.8%). GST-E6 antibodies accounted for a low to moderate proportion of variability in HPV16 and HPV18 GST-E6 (R2 = 6.4%-62.2%). CONCLUSIONS: Associations between naturally induced HPV-specific antibodies depend on phylogenetic relatedness.

Chronic metformin intake and gastric cancer: A pooled analysis within the Stomach cancer Pooling (StoP) Project.

INTRODUCTION: The association between chronic use of metformin and risk of gastric cancer (GC) has been investigated with contradicting results. We aimed to study the association between chronic use of metformin and GC by using data from the Stomach cancer Pooling (StoP) Project, an epidemiological consortium of case-control studies on GC. METHODS: Data from three studies of the StoP Project with available information on metformin intake were analyzed. Multivariable logistic regression models were used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic use of metformin and GC risk. Analyses were adjusted for sex, age, socioeconomic status, body mass index, smoking status, alcohol drinking status, and history of diabetes. Study-specific ORs and 95% CIs were then pooled with a random-effects model. The dose-response relationship between the duration of metformin intake and GC was assessed with a one-stage logistic model, and the duration of intake was modelled using second-order fractional polynomials. RESULTS: The OR of GC in metformin users versus non-users was 1.01 (95% CI=0.61, 1.67). The association between metformin and GC did not change among different strata of study participants' characteristics or when restricting the analyses to those with a history of diabetes. The dose-response analysis showed a slightly reducing trend in the OR of GC and a borderline significant association with increasing duration of metformin intake. CONCLUSIONS: The results of our study do not clearly support an association between chronic use of metformin and GC, warranting further research.

Risk and Survival of Third Primary Cancers in a Population-Based Cohort of Breast Cancer Patients.

Introduction: The growing number of women diagnosed with breast cancer (BCa) together with high survival has resulted in an increasing population of survivors at risk of subsequent primary cancers. This study aimed to estimate the long-term risk and survival of third primary cancers (TPCs) among females with a first primary BCa. Methods: Breast first primary cancers (FPCs) from the Portuguese North Region Cancer Registry, diagnosed between 2000 and 2010 (n = 15,981), were followed for a TPC (December 31, 2015) and death from any cause (June 30, 2021). The cumulative incidence of and mortality among TPCs were estimated. To compare survival, female patients with a TPC were matched (1:1, by age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC + SPC patients without a TPC. Results: Overall, 67 (0.4% of FPCs and 5.4% of SPCs) TPCs were diagnosed. The most common TPC sites were digestive, breast, and female genital organs. Among all FPCs, the 15-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.69% (0.47-0.90%) and among SPCs, 7.21% (4.99-9.43%). The 15-year cumulative mortality of TPCs and matched patients was 70.0% and 51.5%, respectively. For TPCs, compared to matched SPC only patients, the age-adjusted hazard ratio (95% CI) for death was 2.86 (1.61-5.07). Discussion/Conclusion: The most common TPC sites were digestive, breast, and female genital organs, with a 15-year cumulative incidence of 0.69% among FPCs. TPCs had a worse long-term survival compared to patients with an SPC only.