Large Population-based Case Control Research Articles

Outdoor artificial light at night, air pollution, and risk of childhood acute lymphoblastic leukemia in the California Linkage Study of Early-Onset Cancers

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children (age 0–14 years); however, the etiology remains incompletely understood. Several environmental exposures have been linked to risk of childhood ALL, including air pollution. Closely related to air pollution and human development is artificial light at night (ALAN), which is believed to disrupt circadian rhythm and impact health. We sought to evaluate outdoor ALAN and air pollution on risk of childhood ALL. The California Linkage Study of Early-Onset Cancers is a large population-based case–control in California that identifies and links cancer diagnoses from the California Cancer Registry to birth records. For each case, 50 controls with the same year of birth were obtained from birth records. A total of 2,782 ALL cases and 139,100 controls were identified during 2000–2015. ALAN was assessed with the New World Atlas of Artificial Night Sky Brightness and air pollution with an ensemble-based air pollution model of particulate matter smaller than 2.5 microns (PM2.5). After adjusting for known and suspected risk factors, the highest tertile of ALAN was associated with an increased risk of ALL in Hispanic children (odds ratio [OR] = 1.15, 95% confidence interval [CI] 1.01–1.32). There also appeared to be a borderline association between PM2.5 level and risk of ALL among non-Hispanic White children (OR per 10 µg/m3 = 1.24, 95% CI 0.98–1.56). We observed elevated risk of ALL in Hispanic children residing in areas of greater ALAN. Further work is needed to understand the role of ALAN and air pollution in the etiology of childhood ALL in different racial/ethnic groups.

Aspirin, Risk of Colorectal Cancer, & Genetic Risk-Letter.

We read with interest the study by Bakshi and colleagues in which they explored the association between genetic susceptibility to colorectal cancer and aspirin, using a 95-variant colorectal cancer polygenic risk score (PRS) in the participants of ASPREE (ASPirin in Reducing Events in the Elderly) trial (1). The ASPREE trial was a prospective double-blinded, placebo-controlled randomized trial in which 12,609 individuals of European descent ages ≥70 years were enrolled. They concluded that the 95-SNP PRS continues to identify individuals at higher risk of colorectal cancer, including individuals with no family history of colorectal cancer. Recently, Chen and colleagues, using data collected from a large population-based case–control study on colorectal cancer in Germany, analyzed PRS based on 140 colorectal cancer–related risk loci to quantify the genetic risk, reported that regular use of NSAIDs, including aspirin, was associated with significantly reduced colorectal cancer risk regardless of individual genetic profile (2). However, randomization of aspirin treatment in the ASPREE trial was not associated with a reduced incidence of colorectal cancer (P = 0.7).Also, a pooled analysis of two large U.S. cohort studies was published, the Nurses’ Health Study and Health Professionals Follow-up Study, with a total of 94,540 participants ages ≥70 years old (3). The analysis showed that initiating aspirin at an older age was not associated with a lower risk of colorectal cancer. In contrast, those who used aspirin before age 70 years and continued into their 70s or later had a reduced risk of colorectal cancer. A possible explanation is that a beneficial effect of aspirin for colorectal cancer requires at least 5 to 10 years of use (3).Over the last decades, aspirin has been an extensively prescribed drug with antiplatelet and anti-inflammatory effects (4). The mechanism of aspirin's possible anticancer effect is under investigation, but it is believed that it is through inhibiting catalytic enzymes COX-1 and COX-2 involved in prostaglandin synthesis. Therefore, in subjects taking aspirin, gut microbiome composition will shift toward a lower proportion of proinflammatory, colorectal cancer–predisposing bacteria (e.g., Fusobacteria) and a higher proportion of anti-inflammatory, colorectal cancer–protective bacteria (e.g., butyrate-producing bacteria; ref. 5).The recent study by Bakshi and colleagues and other recent high impacted trials on the effect of aspirin on cardiovascular disease and colorectal cancer risks have high translational values into the daily practice. However, there is a need for future preclinical and clinical trials on the impact of aspirin on gut microbiota and their metabolic and immunoregulatory potential.See the Response, p. 703No disclosures were reported.

Levothyroxine use and the risk of colorectal cancer: a large population-based case-control study.

ObjectiveWhether an association between oral levothyroxine use, leading to supraphysiological exposure of the colon to thyroid hormones, and risk of colorectal cancer exists in humans is unclear. We therefore aimed to assess whether the use of levothyroxine is associated with a reduced risk of colorectal cancer in a linked cohort of pharmacy and cancer data.DesignPopulation-based matched case–control study.MethodsA total of 28,121 patients diagnosed with colorectal cancer between 1998 and 2014 were matched to 106,086 controls. Multivariable logistic regression was used to estimate the association between levothyroxine use and occurrence of colorectal cancer, adjusted for potential confounders. Results were stratified by gender, age, tumour subtype, and staging, as well as treatment duration and dosing.ResultsA total of 1066 colorectal cancer patients (4%) and 4024 (4%) controls had used levothyroxine at any point before index date (adjusted odds ratio 0.95 (0.88–1.01)). Long-term use of levothyroxine was seen in 323 (30%) colorectal cancer patients and 1111 (28%) controls (adjusted odds ratio 1.00 (0.88–1.13)). Stratification by tumour subsite showed a borderline significant risk reduction of rectal cancer, while this was not seen for proximal colon cancer or distal colon cancer. There was no relationship with treatment duration or with levothyroxine dose.ConclusionsIn this study, no reduced risk of colorectal cancer was seen in levothyroxine users. When stratifying by tumour subsite, a borderline significant risk reduction of rectal cancer was found and may warrant further research.

Exposure to Nitrate from Drinking Water and the Risk of Childhood Cancer in Denmark

BACKGROUND AND AIM: There is limited evidence that nitrate, a common contaminant in drinking water, increases the risk of childhood cancers. Our objective was to examine this association in a large population based case control study in Denmark with high quality estimates of individual exposures to nitrate in drinking water.. METHODS: We conducted a nationwide case-control study based on all singletons liveborn to Danish-born parents from 1991 to 2015 (N=1,219,140) that included 596 leukemias, 180 lymphomas, and 310 central nervous system cancers (CNS) who were 15 years of age at diagnosis and were identified from the Danish Cancer Registry. Approximately 100 controls were randomly selected and matched to each case on date of birth and sex. Nitrate measurements in public water systems were linked with an address registry to estimate individual average nitrate concentrations during preconception, prenatal, and postnatal periods. Odd ratios (OR) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression controlling for the matching variables, and birth order, birthweight, urbanicity, maternal education, employment, income and smoking, and parental age. RESULTS:There was no evidence of an association of nitrate with leukemia or lymphoma. An association between CNS and the highest category of nitrate exposure (25 mg/L nitrate) was observed for preconception (OR=1.82, 95%CI=1.09 to 3.04), prenatal (OR=1.65, 95%CI=0.97 to 2.81), and postnatal exposure (OR=1.48, 95%CI=0.82 to 2.68) in fully-adjusted models. There was also some evidence of an exposure-response in models of continuous nitrate exposure and CNS. CONCLUSIONS:Our findings provide some evidence that exposure to nitrate from drinking water may increase the risk of childhood CNS cancer, but not leukemia or lymphoma. Exposures in this study were generally well below current European and US maximum allowable concentrations, which in addition to previous studies, raises concerns about the adequacy of these standards for protecting children's health. KEYWORDS: nitrate, drinking water, childhood leukemia, lymphoma and central nervous system cancer

The effect of family history on screening procedures and prognosis in breast cancer patients - Results of a large population-based case-control study

BackgroundThe potential benefit of additional breast cancer screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear. MethodsA large population-based case–control study on breast cancer in postmenopausal women in Germany recruited 2002–2005 (3813 cases and 7341 age-matched controls) was used to assess the association of family history with breast cancer risk. Analysis of family history, participation in screening procedures, and tumor size regarding prognosis in patients was based on follow-up data until 2015. ResultsA first degree family history of breast cancer was associated with higher breast cancer risk (OR 1.39, p < 0.001). Patients with a first degree family history of breast cancer were more likely to have had >10 mammograms (MG) (42.7% vs. 24.9%, p < 0.001) and showed a higher rate of imaging-detected tumors (MG or ultrasound) (45.8% vs. 31.9%, p < 0.001). A smaller tumor size at initial diagnosis (below 2 cm) was more likely in patients with a positive family history (OR 1.45, p < 0.001) and a higher number of MG (≥10 MG: OR 2.29). After accounting for tumor characteristics, mammogram regularity (HR 0.72, p < 0.001) and imaging-assisted tumor detection (HR 0.66, p < 0.001) were associated with better overall survival but not with a positive family history. DiscussionPatients with a positive family history had a higher rate of imaging detected tumors with smaller size at initial diagnosis compared to patients without affected family members. Screening was associated with improved survival after a breast cancer diagnosis, irrespective of a positive family history.

The role of dietary antioxidant index and index of nutritional quality in MS onset: finding from an Iranian population-based incident case–control study

ABSTRACT Introduction: The role of nutritional factors in MS etiology is a matter of debate. Employing dietary antioxidant index (DAI) as well as index of nutritional quality (INQ) we aimed to investigate the possible link between diet and MS risk. Methods This was a large population-based case–control study recruiting 547 incident cases and 1057 population controls between August 2013 and February 2015. DAI and INQ were calculated based on the adolescence dietary intake of the participants. Logistic regression was employed for estimating adjusted odds ratios (OR) and their 95% confidence interval in 2018. Results Participants with less than median DAI values had two-fold increased risk of MS onset (adjusted OR 2.05, 95% CI: 1.64–2.58, P < 0.001). A significant dose–response pattern for DAI (adjusted OR 1.35, 95% CI: 1.18–1.55, P for trend <0.001) was also detected. In the case of INQ, the strongest decreased risk were detected for vitamin D (OR = 0.09) and Zinc (OR = 0.34), followed by vitamin A (OR = 0.49), Calcium (OR = 0.49) and vitamin B6 (OR = 0.51) (All P-values < 0.05). Conclusion Considering the inherent limitation of case–control designs, an appropriate intake of nutrient antioxidants may have a role in decreasing the likelihood of MS risk. Moreover, those with healthier diet assessed by index of nutritional quality were at decreased risk for MS.

Firefighter occupation is associated with increased risk for laryngeal and hypopharyngeal squamous cell carcinoma among men from the Greater Boston area

ObjectiveFirefighters are exposed to a wide variety of carcinogens during the line of duty, including several associated with head and neck cancer. Existing studies assessing head and neck cancer risk...

TL 18040 - Venous thromboembolism risk in foot and ankle surgical patients

Introduction: Venous thromboembolism (VTE) is the leading cause of preventable hospital death. There are several risk factors for VTE, of which orthopedic surgery is an important one. VTE risk is highest following major orthopedic surgery, and therefore, some form of prophylactic therapy is usually recommended. In contrast, the risk for VTE following foot and ankle surgery is less clear, as are guidelines on VTE prophylaxis in these patients. Objective: To estimate the risk of VTE and the duration of the increased risk period after foot and ankle surgery. Methods: Data from a large population-based case–control study (the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis [MEGA] study) on the etiology of venous thrombosis were used (4721 cases; 5638 controls). Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex and body mass index (ORadj), were calculated for patients undergoing any foot or ankle intervention before the index date (VTE date or control date). Results: The 263 cases and 94 controls underwent any orthopedic intervention in the year before the index date for an ORadj of 3,74 (95% CI 2,91-4,80) The ORadj in the first 90 days was 11,35 (95% CI 7,28-17,70). Fifty-five cases and 20 controls had a foot or ankle intervention in the year before the index date, resulting in a three-fold increased risk for VTE (OR 3,29, 95% CI 1,98-5,49). VTE risk was highest in the first 30 (ORadj 10,15 (95% CI 3,04-33,85)) and 90 days following surgery (ORadj 12,42, 95% CI 4,43-34,84). In 34 patients, the surgery was trauma-related, while 43 patients underwent elective surgery. Traumatic surgery was associated with a higher risk than elective surgery with an OR of 13,85 (95% CI 1,77-108,36) and 8,32 (95% CI 1,87-36,94), respectively, at 30 days. Conclusion: Foot and ankle procedures were associated with an increased VTE risk, which was highest in the first 90 days following surgery. Trauma-related surgery was associated with a higher VTE risk than elective surgery. These results are important for decisions regarding thromboprophylactic measures following foot and ankle surgery.

Estimating Venous Thromboembolism Risk in Foot and Ankle Surgical Patients: A Base-Population Case-Control Study

Category:ComplicationsIntroduction/Purpose:Venous thromboembolism (VTE) is the leading cause of preventable hospital death. There are several risk factors for VTE of which orthopedic surgery is an important one. VTE risk is highest following major orthopedic surgery and therefore some form of prophylactic therapy is usually recommended here. In contrast, the risk for VTE following foot and ankle surgery is less clear and so are guidelines on VTE prophylaxis in these patients. The purpose is to estimate the risk of VTE and the duration of the increased risk period after foot and ankle surgery.Methods:Data from a large population-based case–control study (the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis [MEGA] study) on the etiology of venous thrombosis were used (5129 cases; 5882 controls). Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex and body mass index (ORadj) were calculated for patients undergoing any foot or ankle intervention before the index date (VTE date or control date).Results:286 cases and 96 controls underwent any orthopedic intervention in the year before the index date for an ORadj of 3.7 (95%CI 2.9-4.8) The ORadj in the first 90-days was 11.4 (95%CI 7.3-17.7). 57 cases and 20 controls had a foot or ankle intervention in the year before the index date, resulting in a three-fold increased risk for VTE (OR 3.3, 95% CI 1,9-5.5). VTE risk was highest in the first 30 (ORadj 10.2,95%CI 3.0-33.9) and 90-days following surgery (ORadj 12.4, 95% CI 4.4-34.8). In 34 patients the surgery was trauma related while 43 patients underwent elective surgery. Traumatic surgery was associated with a higher risk compared with elective surgery for an OR of 13.9 (95%CI 1.8-108.4) and 8.3 (95%CI 1.9-36.9), respectively at 30-days.Conclusion:Foot and ankle procedures were associated with an increased VTE risk which was highest in the first 90-days following surgery. Trauma related surgery was associated with a higher VTE risk than elective surgery. These results are important to decide on thromboprophylactic measures following foot and ankle surgery.

Development of a Job-Exposure Matrix for Assessment of Occupational Exposure to High-Frequency Electromagnetic Fields (3 kHz-300 GHz).

The aim of this work was to build a job-exposure matrix (JEM) using an international coding system and covering the non-thermal intermediate frequency (IF) (3-100 kHz, named IFELF), thermal IF (100 kHz-10 MHz, named IFRF), and radiofrequency (RF) (>10 MHz) bands. Detailed occupational data were collected in a large population-based case-control study, INTEROCC, with occupations coded into the International Standard Classification of Occupations system 1988 (ISCO88). The subjects' occupational source-based ancillary information was combined with an existing source-exposure matrix and the reference levels of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) for occupational exposure to calculate estimates of level (L) of exposure to electric (E) and magnetic (H) fields by ISCO88 code and frequency band as ICNIRP ratios (IFELF) or squared ratios (IFRF and RF). Estimates of exposure probability (P) were obtained by dividing the number of exposed subjects by the total number of subjects available per job title. With 36 011 job histories collected, 468 ISCO88 (four-digit) codes were included in the JEM, of which 62.4% are exposed to RF, IFRF, and/or IFELF. As a reference, P values for RF E-fields ranged from 0.3 to 65.0% with a median of 5.1%. L values for RF E-fields (ICNIRP squared ratio) ranged from 6.94 × 10-11 to 33.97 with a median of 0.61. The methodology used allowed the development of a JEM for high-frequency electromagnetic fields containing exposure estimates for the largest number of occupations to date. Although the validity of this JEM is limited by the small number of available observations for some codes, this JEM may be useful for epidemiological studies and occupational health management programs assessing high-frequency electromagnetic field exposure in occupational settings.

Chrysotile fibers in tissue adjacent to laryngeal squamous cell carcinoma in cases with a history of occupational asbestos exposure.

Asbestos describes a group of naturally occurring fibrous silicate mineral compounds that have been associated with a number of respiratory maladies, including mesothelioma and lung cancer. Additionally, based primarily on epidemiologic studies, asbestos has been implicated as a risk factor for laryngeal and pharyngeal squamous cell carcinoma (SCC). The chief objective of this work was to strengthen existing evidence via empirical demonstration of persistent asbestos fibers embedded in the tissue surrounding laryngeal and pharyngeal SCC, thus providing a more definitive biological link between exposure and disease. Six human papillomavirus (HPV)-negative laryngeal (n = 4) and pharyngeal (n = 2) SCC cases with a history working in an asbestos-exposed occupation were selected from a large population-based case-control study of head and neck cancer. A laryngeal SCC case with no history of occupational asbestos exposure was included as a control. Tissue cores were obtained from adjacent non-neoplastic tissue in tumor blocks from the initial primary tumor resection, and mineral fiber analysis was performed using a scanning electron microscope equipped with an energy dispersive x-ray analyzer (EDXA). Chrysotile asbestos fiber bundles were identified in 3/6 of evaluated cases with a history of occupational asbestos exposure. All 3 cases had tumors originating in the larynx. In addition, a wollastonite fiber of unclear significance was identified one of the HPV-negative pharyngeal SCC cases. No mineral fibers were identified in the adjacent tissue of a case without occupational exposure. The presence of asbestos fibers in epithelial tissue surrounding laryngeal SCC in cases with a history of occupational asbestos exposure adds a key line of physical evidence implicating asbestos as an etiologic factor.

Abstract 1420: Prevalence of PALB2 mutations in an unselected cohort of breast cancer patients and unaffected individuals from Malaysia and Singapore

Abstract Background: Rare variants such as protein truncating and splice-junction variants in PALB2 have been found to confer increased risk to breast cancer. However, previous studies have only investigated the prevalence of mutation carriers in individuals selected on the basis of earlier age of diagnosis or on family history of breast cancer. In this study, we sought to determine the prevalence of PALB2 in an unselected hospital-based multi-ethnic cohort of breast cancer cases and healthy women from Malaysia and Singapore. Method: Amplicon-based targeted sequencing of the PALB2 gene which include all coding exons and splice site junctions was performed to identify germline alterations in an unselected cohort of 5021 affected and 5192 healthy individuals recruited from multiple centres. Associations between pathogenic (protein truncating) variants and breast cancer risk were evaluated using logistic regression and a Fisher's exact test. Results: Truncating variants in PALB2 were associated with increased risk of breast cancer with an estimated OR=6.61 (95% CI 3.27 to 13.37, p&amp;lt;0.0001). In total, there were 31 unique protein truncating variants identified in 66 individuals (57 cases [1.1%], 9 controls [0.2%]). The majority of these truncating variants were rare; of the 31 unique variants identified, 18 (58%) were found only in 1 individual. The common truncating variants in our cohort were PALB2 c.2968G&amp;gt;T (p.Glu990Ter, rs876659036) found in 5 cases and 2 controls; PALB2 c.1037_1041delAAGAA (p.Lys346Thrfs, rs587776410) found in 4 cases and PALB2 c.1059delA (p.Lys353Asnfs, rs730881872) found in 4 cases. Of the PALB2 carriers, 24% developed ER+/HER2- disease, 14.0% developed ER+/Her2+ or ER-/Her2+ disease and 10.5% developed triple negative breast cancer. Conclusions: We found that 1.1% of breast cancer patients and 0.2% of unaffected individuals carry a pathogenic mutation in PALB2. To the best of our knowledge, this is the first large population-based case control study that was able to estimate the breast cancer risk associated with truncating mutations in PALB2 gene in a multi-ethnic population in South East Asia. Citation Format: Patsy P. Ng, Wei Xiong Wen, Eldarina Wijaya, Jamie Allen, Joanna Lim, Shao Yan Lau, Brennan Decker, Karen Pooley, Leila Dorling, Craig Luccarini, Caroline Baynes, Don Conroy, Patricia Harrington, Shivaani Mariapun, Siti Norhidayu Hasan, Daphne Shin-Chin Lee, Sheau Yee Lee, Sook Yee Yoon, Cheng Har Yip, Nur Aishah Taib, Weang Kee Ho, Mikael Hartman, Antonis C Antoniou, Alison M Dunning, Douglas F Easton, Soo Hwang Teo. Prevalence of PALB2 mutations in an unselected cohort of breast cancer patients and unaffected individuals from Malaysia and Singapore [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1420.

Abstract P5-08-21: The effect of family history on screening procedures and prognosis in breast cancer patients – Results of a large population-based case–control study on breast cancer

Abstract Background: Patients with a first- or second-degree family history of breast or ovarian cancer participate more frequently in breast cancer screening procedures. A benefit of additional screening visits has been documented in high-risk patients with (e.g. BRCA 1, BRCA 2 gene mutations). However, the potential benefit of additional screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear. Methods: Patients were recruited in 2002–2005 within a large population-based case–control study on breast cancer in Germany (3,813 cases and 7,341 age-matched healthy controls). Univariate and multivariate analyses were performed to evaluate the effect of family history on breast cancer risk, participation in screening procedures, tumor size and prognosis. Results A higher breast cancer risk was observed in patients with a positive family history (1 affected family member: OR 1.32, p&amp;lt;0.001). Patients with a 1st degree positive family history received a higher number of mammograms (MG) (&amp;gt;10 MG: 42.7% vs. 24.9%, p&amp;lt;0.001) and showed a higher rate of imaging-detected tumors (mammogram or ultrasound) (45.8% vs. 31.9%, p&amp;lt;0.001) compared to patients without positive family history. Positive family history (OR 1.45 pT1 vs. ≥pT2, p&amp;lt;0.001) and higher number of mammograms (≥10 mammograms: OR 2.29 pT1 vs. ≥pT2) were associated with smaller tumor size at initial diagnosis. Additionally, there was a significant association between mammogram regularity (HR 0.72, p&amp;lt;0.001) and imaging-assisted tumor detection (HR 0.66, p&amp;lt;0.001) with improved overall survival. However, no significant association between a positive family history of breast cancer and survival could be seen. Discussion: Patients with a family history of breast cancer participated more frequently in screening procedures and had a higher rate of image-detected tumors with smaller size at initial diagnosis, compared to patients without affected family members. Breast cancer screening procedures were significantly associated with improved survival. Citation Format: Seiffert K, Thoene K, zu Eulenburg C, Rudolph A, Schmalfeldt B, Flesch-Janys D, Chang-Claude J, Witzel I. The effect of family history on screening procedures and prognosis in breast cancer patients – Results of a large population-based case–control study on breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-21.

Preeclampsia and preterm delivery: A population-based case–control study

ABSTRACTObjective: To determine the contribution of preeclampsia toward preterm birth in primiparous women. Methods: This large population-based case–control study used the Aberdeen Maternity and Neonatal Databank to analyze data on primiparous women with singleton pregnancies, who delivered between 1997 and 2012.Results: A significant positive association was found between preeclampsia and preterm birth (adjusted odds ratio 4.43; 95% confidence interval 3.80–5.16). Magnitude of association varied according to the onset of delivery and year of delivery. Conclusion: Preeclampsia is an important contributor to preterm delivery in this setting and therefore a potentially useful condition to target in order to reduce preterm rates.

Population attributable risks of oral cavity cancer to behavioral and medical risk factors in France: results of a large population-based case-control study, the ICARE study.

BackgroundPopulation attributable risks (PARs) are useful tool to estimate the burden of risk factors in cancer incidence. Few studies estimated the PARs of oral cavity cancer to tobacco smoking alone, alcohol drinking alone and their joint consumption but none performed analysis stratified by subsite, gender or age. Among the suspected risk factors of oral cavity cancer, only PAR to a family history of head and neck cancer was reported in two studies. The purpose of this study was to estimate in France the PARs of oral cavity cancer to several recognized and suspected risk factors, overall and by subsite, gender and age.MethodsWe analysed data from 689 oral cavity cancer cases and 3481 controls included in a population-based case–control study, the ICARE study. Unconditional logistic regression models were used to estimate odds ratios (ORs), PARs and 95 % confidence intervals (95 % CI).ResultsThe PARs were 0.3 % (95 % CI −3.9 %; +3.9 %) for alcohol alone, 12.7 % (6.9 %–18.0 %) for tobacco alone and 69.9 % (64.4 %–74.7 %) for their joint consumption. PAR to combined alcohol and tobacco consumption was 74 % (66.5 %–79.9 %) in men and 45.4 % (32.7 %–55.6 %) in women. Among suspected risk factors, body mass index 2 years before the interview <25 kg.m−2, never tea drinking and family history of head and neck cancer explained 35.3 % (25.7 %–43.6 %), 30.3 % (14.4 %–43.3 %) and 5.8 % (0.6 %–10.8 %) of cancer burden, respectively. About 93 % (88.3 %–95.6 %) of oral cavity cancers were explained by all risk factors, 94.3 % (88.4 %–97.2 %) in men and only 74.1 % (47.0 %–87.3 %) in women.ConclusionOur study emphasizes the role of combined tobacco and alcohol consumption in the oral cavity cancer burden in France and gives an indication of the proportion of cases attributable to other risk factors. Most of oral cavity cancers are attributable to concurrent smoking and drinking and would be potentially preventable through smoking or drinking cessation. If the majority of cases are explained by recognized or suspected risk factors in men, a substantial number of cancers in women are probably due to still unexplored factors that remain to be clarified by future studies.

The joint effect of asbestos exposure, tobacco smoking and alcohol drinking on laryngeal cancer risk: evidence from the French population-based case–control study, ICARE

ObjectiveThe objective of the study was to investigate the joint effect of occupational exposure to asbestos, and tobacco and alcohol consumption, on the risk of laryngeal cancer among men.MethodsWe used...

Metabolic syndrome and prostate cancer risk in a population-based case-control study in Montreal, Canada.

BackgroundThe role of metabolic syndrome (MetS) in prostate cancer risk is still debated. We investigated it in a large population-based case–control study.MethodsCases were 1937 men with incident prostate cancer, aged ≤75 years, diagnosed across French hospitals in the Montreal area between 2005 and 2009. Concurrently, 1995 population controls from the same residential area and age distribution were randomly selected from electoral list of French-speaking men. Detailed lifestyle and medical histories, and anthropometric measures, were collected during in-person interviews. Prevalence of MetS components (type 2 diabetes, high blood pressure, dyslipidemia and abdominal obesity) was estimated at 2 years before diagnosis for cases/ interview for controls, and at ages 20, 40, 50 and 60. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals for the association between MetS and prostate cancer risk.ResultsA history of MetS (≥3 components vs <3) was associated with a reduced risk of prostate cancer (OR = 0.70 [0.60, 0.82]) after considering potential confounders. The negative association was particularly pronounced with a young age (≤40 years) at MetS onset (OR = 0.38 [0.16-0.89]), did not vary according to prostate cancer aggressiveness, and was only partly explained by the presence of type 2 diabetes. A risk decrease was observed with the number of MetS components, suggesting a synergistic interaction of the components.DiscussionThe observed negative association, consistent with results from other North American populations undergoing regular prostate cancer screening, underlines the importance of considering PSA-testing when studying the MetS-prostate cancer association.ConclusionsFindings from this study are consistent with an inverse association between MetS and prostate cancer risk.

Hodgkin lymphoma risk following infectious and chronic inflammatory diseases: a large population-based case-control study from Sweden.

Patients with Hodgkin lymphoma (HL) have a well-characterized immune deficiency of T cell function, originally identified by increased susceptibility to certain infections. Epidemiological evidence has long pointed to infectious etiologies in younger HL patients. With the aim of expanding our knowledge on the potential role of pre-existing immune deficiency in HL and an infectious/inflammatory etiology, we conducted a comprehensive population-based case-control study in HL patients diagnosed in Sweden in the period 1965-2004, and their matched controls. In a large population-based study including 7,414 HL patients and 29,240 matched controls, we evaluated the subsequent risk of HL in relation to a broad range of infectious and inflammatory conditions, using unconditional logistic regression. A previous history of any reported infection was associated with an 11 % increased risk of HL (P < 0.05). More specifically, we found sinusitis (odds ratio = 1.81; 95 % confidence interval = 1.06-3.07), tuberculosis (1.76; 1.01-3.07), encephalitis (7.88; 1.97-31.5), and herpes zoster (2.20; 1.11-4.35) to be associated with excess HL risk. A personal prior history of chronic inflammatory condition was not associated with an increased risk of HL (0.94; 0.71-1.14). Our results suggest that underlying immune deficiency is a primary phenomenon in HL. Alternatively, certain infectious agents may be potential HL triggers.

Asthma, allergy and the risk of prostate cancer: Results from the Montreal PROtEuS study

BackgroundThe few previous studies examining the association between asthma or allergy and prostate cancer (PCa) risk were inconclusive. This study aimed to evaluate these associations, and to explore in details the possible influence of current versus former allergic condition, age at onset, time since onset, and duration of each allergic condition. MethodsDetailed information on self-reported asthma and allergy was collected in the context of a large population-based case–control study conducted in Montreal, Canada. Study subjects included 1936 cases, diagnosed between 2005 and 2009, and 1995 population controls. Unconditional multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, ancestry and familial history of prostate cancer. ResultsThe ORs were 1.11 (95% CI: 0.89–1.40) and 0.98 (95% CI: 0.84–1.14) for ever reporting of asthma and allergy, respectively. These ORs did not substantially vary according to status (former or current), age at onset, time since onset, and duration of each allergic condition. PCa screening was not associated with allergic diseases reporting. ConclusionsOverall, our findings are in line with the absence of an association between a history of asthma or allergy, and PCa risk.

Abstract 4320: Mitochondrial DNA copy number in peripheral blood and the risk of clear-cell renal cell carcinoma: Effect of age, gender, smoking, and history of hypertension

Abstract Mitochondria are the primary source of cellular energy. Mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) has high genetic heritability and inter-individual variation of mtDNA copy number in PBLs has been associated with the risk of several human cancers. In this study, we investigated into the link between mtDNA and clear-cell renal cell carcinoma (ccRCC) in a large population-based case control study. We measured relative mtDNA copy number in PBLs from 616 Caucasian ccRCC cases and 603 controls frequency-matched on age, gender, and ethnicity. In the analyses of controls only, there was a significant inverse correlation between age and mtDNA copy number (P=0.001); men had significantly lower mtDNA copy number than women (P&amp;lt;0.001); and both smoking and hypertension had a negative effect on mtDNA copy number (P=0.03 and 0.04, respectively). We found a significantly lower mtDNA copy number in cases compared to controls (mean±SD: 1.16±0.37 versus 1.21±0.39, P=0.04). Dichotomized at the median level of mtDNA copy number in controls, individuals with lower mtDNA copy number were at an increased risk of ccRCC (OR=1.20, 95% CI: 0.96-1.51, P=0.11) adjusting for age, gender, smoking status, BMI, and history of hypertension in a multivariate logistic regression analysis. In stratified analyses, the association between lower mtDNA copy number and increased ccRCC risks reached statistical significance in younger aged (age&amp;lt;60) individuals (OR=1.56, 95% CI: 1.12-2.15, P=0.01), women (OR=1.57, 95% CI: 1.06-2.35, P=0.03), and individuals without history of hypertension (OR=1.48, 95% CI: 1.08-2.04, P=0.02). Interestingly, there was a significant interaction between age and mtDNA copy number, and between a history of hypertension and mtDNA copy number in elevating ccRCC risk (P for interaction=0.02 and 0.03, respectively). In summary, our data showed that several established risk factors of ccRCC, including advanced age, male sex, smoking, and history of hypertension, negatively impacted mtDNA copy number in PBLs. Lower mtDNA copy number in PBLs was associated with significantly increased risk of ccRCC in younger aged individuals, women, never smokers, and those without a history of hypertension. There was a significant interaction between age and mtDNA, and a history of hypertension and mtDNA in elevating the risk of ccRCC. These findings indicate that the association between mtDNA copy number in PBLs and ccRCC risk may be modified by various host characteristics (age, gender, smoking, and history of hypertension), providing novel insight into the role of mtDNA in modulating RCC tumorigenesis. Citation Format: Xin Wang, Stephanie Melkonian, Jian Gu, David Chang, Nizar Tannir, Christopher Wood, Xifeng Wu. Mitochondrial DNA copy number in peripheral blood and the risk of clear-cell renal cell carcinoma: Effect of age, gender, smoking, and history of hypertension. [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 4320. doi:10.1158/1538-7445.AM2014-4320