Importance Cigarette smoking is a strong risk factor for mortality in patients diagnosed with head and neck squamous cell carcinoma (HNSCC). However, little evidence supports which smoking metric best models the association between smoking and survival in HNSCC. Objective To determine which smoking metric best models a linear association between smoking exposure and overall survival (OS) in patients with HNSCC. Design, Setting, and Participants A retrospective multicenter cohort study of 6 clinical epidemiological studies was performed. Five were part of the Human Papillomavirus, Oral and Oropharyngeal Cancer Genomic Research (VOYAGER) consortium. Participants included patients 18 years and older with pathologically confirmed HNSCC. Data were collected from January 2002 to December 2019, and data were analyzed between January 2022 to November 2024. Main Outcomes and Measures The primary outcome was OS. The performance of 8 smoking metrics, including pack-years, duration, and log cig-years (calculated as log 10 [cigarettes smoked per day + 1] × number of years smoked) for modeling OS were compared. Metric performance was measured by the strength of association in Cox proportional hazard models, linearity based on P for linear trend, Akaike information criterion (AIC; lower value indicates better model fit), and visual assessment of spline curves. Secondary outcomes included modeling OS in clinicodemographic subgroups and HNSCC anatomic subsites. Exploratory outcomes included cancer-specific survival and noncancer survival. Results In total, 8875 patients with HNSCC (2114 [24%] female; median [IQR] age, 61 [54-69] years) were included. Of 8 smoking metrics evaluated, smoking duration (adjusted hazard ratio [aHR], 1.11 [95% CI, 1.03-1.19]) and log cig-years (aHR, 1.11 [95% CI, 1.04-1.18]) had the highest aHRs; both had a statistically significant linear association with OS. Log cig-years had the lowest AIC linear value and the most visually linear spline curve when modeling OS. Duration and log cig-years outperformed pack-years for modeling OS regardless of age, smoking status, and cancer stage. Both performed well in lip and oral cavity, laryngeal (only duration was significant), and human papillomavirus–negative oropharyngeal subsites. In an exploratory analysis, duration had the highest aHR (1.15 [95% CI, 1.02-1.29]), and log cig-years had the lowest AIC linear value when modeling noncancer survival. Conclusions and Relevance In this cohort study, smoking duration and log cig-years best modeled a linear relationship with OS for patients with HNSCC. Both metrics maintained robust performance within specific clinicodemographic subgroups and anatomic subsites. Although most HNSCC survival models control for smoking exposure using smoking status or pack-years, duration and log cig-years may be superior metrics to account for the effects of smoking on survival.

Head and neck squamous cell carcinoma (HNSCC) includes diverse cancers arising in the oral cavity, oropharynx, and larynx, with the main risk factors being environmental exposures such as tobacco, alcohol, and human papillomavirus (HPV) infection. The genetic factors contributing to susceptibility across different populations and tumour subsites remain incompletely understood. Here we show, through a genome-wide association and fine mapping study of over 19,000 HNSCC cases and 38,000 controls from multiple ancestries, 18 genetic risk variants and 11 signals from fine mapping of the human leukocyte antigen (HLA) region, all previously unreported. rs78378222, a regulatory variant for TP53 is associated with a 40% reduction in overall HNSCC risk. We also identify gene-environment interactions, with BRCA2 and ADH1B variants showing effects modified by smoking and alcohol use. Subsite-specific analysis of the HLA region reveals distinct immune-related associations across HPV-positive and HPV-negative tumours. These findings refine the genetic architecture of HNSCC and highlight mechanisms linking inherited variation, immunity, and environmental exposures.

Purpose: Recommendations from Cancer Care Ontario stress the importance of multidisciplinary care from radiologists and urologists for prostate cancer treatment. The present study sought to examine what percentage of patients had a consultation with a radiation oncologist before undergoing a radical prostatectomy in Ontario, Canada, between 2010 and 2019. Methods and Materials: Administrative health care databases were used to analyze the number of consultations billed to the Ontario Health Insurance Plan from radiologists and urologists who treated men with a first prostate cancer diagnosis (n = 22,169). Results: In Ontario, 94.70% of Ontario Health Insurance Plan billings for patients with prostate cancer who had a prostatectomy within 1 year of a prostate cancer diagnosis were from urology, and 37.66% and 1.77% of billings were received from radiation oncology and medical oncology specialties, respectively. When sociodemographic variables were examined, having a lower neighborhood income (adjusted odds ratio [aOR], 0.69; confidence interval [CI], 0.62-0.76) and a rural residence (aOR, 0.72; CI, 0.65-0.79) were associated with lower odds of receiving a consultation from a radiation oncologist. When billings for consultations were examined geographically by region, Northeast Ontario (Local Health Integrated Network 13) had the lowest odds of receiving a radiation consultation compared with the rest of Ontario (aOR, 0.50; CI, 0.42-0.59). Conclusions: The results of this study show that differences in equitable access to multidisciplinary health care exist for men with a first prostate cancer diagnosis who reside in more northern and rural regions within Ontario, relative to the rest of the province. The reasons for these findings are likely multifactorial and may include factors such as patient treatment preference and distance/travel to receive treatment. However, as diagnosis year increased, so did the chances of receiving a radiation oncologist consultation, and this upward trend may reflect the implementation of Cancer Care Ontario guidelines.

Differences in the baseline levels of serum cytokines or in single-nucleotide polymorphisms (SNPs) in cytokine genes may be useful to predict outcomes for patients being treated for metastatic breast cancer. We have measured the plasma levels and characterized individual SNPs for IL-1RA, IL-1β, IL-2, IL-6 and TNFα in 130 patients with metastatic breast cancer treated with high-dose chemotherapy. Patients were treated with high-dose cyclophosphamide (Group 1, 74 patients) or high-dose paclitaxel-containing regimens (Group 2, 56 patients). A high plasma level of IL-1RA and a SNP in the IL-1RA gene indicated a better prognosis for patients in Group 1 (but not Group 2). However, the level of plasma IL-1RA did not correlate with the SNP genotype. A high plasma level of IL-6 or TNFα indicated a poorer outcome for patients in Group 1 although the SNP genotypes for the IL-6 and TNFα SNPs were not associated with differences in outcome. The plasma levels of IL-1β and IL-2 and the genotype of the IL-1β SNPs did not indicate differences in outcome. Although, individually, plasma levels of cytokine or “risk” SNP genotypes may not indicate outcome, in combination there was an increased trend to predict outcome for patients treated with high-dose cyclophosphamide but not high-dose paclitaxel. These results suggest that the immune cytokines may be useful as prognostic biomarkers in the treatment of patients with metastatic breast cancer treated with different types of chemotherapy.

Smoking during cancer treatment is associated with reduced treatment response and cancer recurrence in patients with tobacco-related cancers. The purpose of this study was to examine smoking characteristics in head and neck cancer patients (n = 503) with a history of smoking and examine the impact of an intensive clinical tobacco intervention to patients who were currently smoking. All participants completed an interviewer-administered questionnaire at study enrollment which examined smoking behaviours, motivations to quit, and strategies used to cessate smoking. Follow-up assessments were completed at 6- and 12-months which monitored whether patients had quit smoking, remained cessated, or continued to smoke since study recruitment. For those who were currently smoking (n = 186, 37.0%), an intensive clinical tobacco intervention that utilized the 3A’s—Ask, Advise, Arrange—and the Opt-Out approach was offered to assist with smoking cessation at their new patient visit and followed-up weekly during their head and neck radiation therapy for 7 weeks. At 6 months, 23.7% (n = 41) of those who were smoking successfully quit; 51.2% quit ‘cold turkey’ (defined as using no smoking cessation assistance, aids or pharmacotherapy to quit), while 34.9% used pharmacotherapy (varenicline (Champix)) to quit. On average, it took those who were smoking 1–5 attempts to quit, but once they quit they remained cessated for the duration of the study. Although the head and neck cancer patients in this study reported high levels of nicotine dependence, many were able to successfully cessate.

Purpose:Many patients diagnosed with head-and-neck cancer are current or former smokers. Despite the well-known adverse effects of smoking, continuation of smoking during cancer treatment is associated with reduced efficacy of that treatment and with cancer recurrence. In the present study, we examined smoking characteristics in patients with head-and-neck cancer near the time of cancer treatment.Methods:A prospective cohort of patients with head-and-neck cancer who attended a dental oncology clinic before receiving cancer treatment at a regional cancer centre were invited to participate in a study that involved completing an interviewer-administered questionnaire to assess smoking characteristics, intention to quit, motivation to quit, and strategies perceived to potentially aid in successful cessation.Results:The study enrolled 493 ever-smokers, with a response rate of 96.1% and a self-reported current smoker rate of 37.1% (n = 183). Most of the current smokers reported high nicotine dependence, with 84.7% (n = 155) indicating a time to first cigarette of 30 minutes or less. Most had previously attempted to quit smoking (77.0%), and many had prior unsuccessful quit attempts before resuming smoking again. Most were interested in quitting smoking (85.8%), and many (70.5%) were seriously considering quitting smoking within the subsequent 30 days.Conclusions:Patients with head-and-neck cancer reported high nicotine dependence and high interest in cessation opportunities near the time of treatment for cancer. Those results might provide support for provision of smoking cessation opportunities.

BACKGROUND Access to hospice palliative care may improve quality of life, reduce the use of potentially aggressive end-of-life care and allow for death to occur outside of an acute care hospital. The aim of this study was to examine the impact of an ambulatory hospice palliative care program on end-of-life care compared to care received by a matched control group of deceased patients. METHODS This retrospective study included patients who received hospice palliative care through the Symptom Management Program in Sudbury, Ontario, during 2012-2015. Using linked administrative health records, we defined a propensity-matched control group and derived 4 previously defined variables associated with aggressive end-of-life care (chemotherapy received in the last 2 wk of life, > 1 emergency department visit within 30 d of death, > 1 hospital admission within 30 d of death and at least 1 intensive care unit admission within 30 d of death). We also examined place of death. We measured family/caregiver satisfaction with care 3 months after the patient's death using the FAMCARE questionnaire. RESULTS Of 914 eligible decedents enrolled in the Symptom Management Program, 754 (82.5%) were matched. Receiving care through the program was protective for most measures of aggressive end-of-life care (absolute risk reduction [ARR] 12.73, 95% confidence interval [CI] 12.65-12.81 for any end-of-life care outcome) and death in an acute care setting (ARR 19.89, 95% CI 19.78-20.00). Of the 450 family caregivers invited to complete the FAMCARE questionnaire, 190 (42.2%) returned completed surveys; following data linkage and matching, 96 (21.3%) were available for analysis. Satisfaction with care received within the program appeared high (mean total score 85.72/100). INTERPRETATION Provision of hospice palliative care through this ambulatory program was associated with lower use of aggressive end-of-life care and death outside of an acute care hospital. Improving access could be expected to provide positive benefits at the individual and system level.

The frequencies of circulating myeloid and T-cell populations were correlated with clinical outcome for 88 patients with metastatic breast cancer treated with high-dose chemotherapy. The ability to predict outcome depended on the chemotherapy regimen. The frequency of monocytes indicated outcome for patients treated with cyclophosphamide-based chemotherapy, while the frequency of T cells indicated outcome for patients treated with paclitaxel-based chemotherapy. Background: The frequency of circulating leukocytes has been shown to be a prognostic factor in patients being treated for different types of cancer. In breast cancer, tumor-infiltrating leukocytes may predict patient outcome, but few studies have investigated such associations for circulating leukocytes. Patients and Methods: Multiparametric flow cytometry was used to examine the immunophenotypes of circulating peripheral blood mononuclear cells for 88 patients with metastatic breast cancer, which was then correlated to breast cancer-specific survival. Patients had been treated either with high-dose cyclophosphamide-containing regimens (group 1, n = 51 patients) or high-dose paclitaxel-containing regimens (group 2, n = 37 patients). Results: The frequency of peripheral blood CD14(+) monocytes indicated prognosis for patients in group 1 (but not group 2), while higher levels of CD11c(+) dendritic cells indicated a better prognosis for patients in group 2 (but not group 1). The frequency of a number of different CD4(+) or CD8(+) T cell subtypes also predicted prognosis for patients in group 2. For example, patients in group 2 with a higher frequency of circulating CD4(+) or CD8(+) naive T cells (CD45RA(+)CD95(-)CD27(+)CD28(+)) showed a poorer prognosis. In contrast, T cells were not associated with prognosis for patients in group 1. Conclusion: Circulating leukocytes can predict clinical outcome for patients with breast cancer. Prediction of clinical outcome in this cohort of metastatic breast cancer patients was specific to the type of chemotherapy, and this finding is likely to apply to other therapies.

Background: Access to palliative care has been associated with improving quality of life and reducing the use of potentially aggressive end-of-life care. However, many challenges and barriers exist in providing palliative care to residents in northern and rural settings in Ontario, Canada. Aim: The purpose of this study was to examine access to palliative care and associations with the use of end-of-life care in a decedent cohort of northern and southern, rural and urban, residents. Design: Using linked administrative databases, residents were classified into geographic and rural categories. Regression methods were used to define use and associations of palliative and end-of-life care and death in acute care hospital. Setting/Participants: A decedent cancer cohort of Ontario residents (2007-2012). Results: Northern rural residents were less likely to receive palliative care (adjusted odds ratio [OR] = 0.90, 95% confidence interval [CI]: 0.83-0.97). Those not receiving palliative care were more likely to receive potentially aggressive end-of-life care and die in an acute care hospital (adjusted OR = 1.20, 95% CI: 1.02-1.41). Conclusions: Palliative care was significantly associated with reduced use of aggressive end-of-life care; however, disparities exist in rural locations, especially those in the north. Higher usage of emergency department (ED) and hospital resources at end of life in rural locations also reflects differing roles of rural community hospitals compared with urban hospitals. Improving access to palliative care in rural and northern locations is an important care issue and may reduce use of potentially aggressive end-of-life care.

A smoking cessation intervention at the time of cancer treatment is an important opportunity to improve patient quality of life, treatment outcome, and survival in people with cancer. This prospective observational study was designed to assess intention to quit, motivation to quit, smoking characteristics and interest in smoking cessation, and assessment of cessation following a standardized smoking cessation intervention. The intervention was a limited clinical 5A intervention offered by trained health professionals and occurred within a dental oncology clinic that offered regular follow-up and any needed pharmacotherapy through the course of cancer treatment. The cohort was composed of head and neck cancer patients who were self-reported ever-smokers at enrolment and who attended the Northeast Cancer Centre, a regional cancer centre in Northeastern Ontario, Canada, for cancer treatment. There were 377 cancer patients who participated in study, with 35.8% (n = 135/377) self-reporting as current smokers. Most current smokers had high nicotine dependence, with 82.2% (n = 111/135) reporting a time to first cigarette (TTFC) of 30 minutes or less; 84.4% (n = 114/135) were interested in quitting smoking. By 1 year post intervention 10 patients had died and 28 patients were lost to follow-up; of the remainder 29 smokers had cessated yielding a cessation rate of 29.9% (n = 29/97); or 23.2% (n = 29/125) conservatively assuming those lost to follow-up remained current smokers. Offering comprehensive smoking cessation during the course of cancer treatment yields long term smoking cessation benefits in a cohort of patients with smoking associated cancers. Citation Format: Michael S.C. Conlon, Deborah P. Saunders. Smoking cessation following a limited 5A intervention in a cohort of patients with head and neck cancer attending for treatment at a regional cancer program in Ontario, Canada. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3461.

Previously published findings have documented increased breast cancer risks associated with the nursing profession. The aim of the present study was to assess whether an increased risk of breast cancer was associated with nursing in a population-based case–control breast cancer study of women in Northeastern Ontario, Canada.

Abstract Transforming growth factor-beta1 (TGFB1) is a multifunctional cytokine that may play an important role in the development and progression of cancer. The results of a number of association studies of TGFB1 polymorphisms and breast cancer risk are inconclusive. This study examined 4 single nucleotide polymorphisms (SNPs) in TGFB1 and risk of breast cancer using data previously collected from a population based case-control study (n=307 cases and 664 controls) of Caucasian women conducted in Northeastern Ontario, Canada. The SNPs (rs8179181, rs8110090, rs1800470 (L10P), rs1800469 (-509C/T)) were selected as either tag SNPs or had been identified as potentially functional in other studies, and were analysed using Taqman genotyping assays. Two of the SNPs were at the 5’ end (rs1800469 (-509C/T), rs1800470) and were in high LD (D’ 0.98); the remaining SNPs (rs8179181, rs8110090) were at the 3’ end and were also in high LD (D’ 0.99). In single-SNP analyses, the variant homozygous genotypes in rs1800470 (CC) and rs8179181 (AA) were significantly protective in the codominant model with Odds Ratios (OR) and 95% Confidence Intervals (95% CIs) of 0.63 (0.40-0.99) and 0.45 (0.21-0.96), while the AG genotype of rs8110090 was significantly associated with increased breast cancer risk with an OR of 1.78 (95% CI 1.14-2.77). Of the seven estimated haplotypes, 3 were significantly protective for breast cancer; when compared to the referent haplotype (see Table). In conclusion, our results suggest that SNPs at both the 3’ and 5’ end of TGFB1 may be associated with risk of breast cancer, and future studies examining additional polymorphisms in these regions would be valuable. Haplotype association with breast cancer risk (n = 969; Global Haplotype Association p-value 0.0021)rs8179181rs8110090rs1800470rs1800469FrequencyOR (95% CI)P-value1GATC0.40281.002GACT0.23870.73 (0.55–0.97)0.033AATC0.17280.67 (0.48–0.93)0.0174GACC0.06710.49 (0.30–0.81)0.00545AACT0.0560.55 (0.30–1.00)0.0526GGTC0.02981.00 (0.48–2.09)0.997GGCT0.02271.82 (0.82–4.06)0.14 Citation Format: Mary A. Bewick, Michael SC Conlon. A population-based study of Transforming Growth Factor-Beta1 (TGFB1) polymorphisms and risk of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1336. doi:10.1158/1538-7445.AM2013-1336

Abstract There are high rates of smoking among head and neck cancer patients, and successful smoking cessation may offer a treatment and survival benefit for these patients. This prospective study was designed to assess baseline smoking characteristics, and intention to quit in a cohort of patients with head and neck cancer. All patients attended the dental oncology clinic within the regional cancer centre for assessments before, during, and after primary treatment. Primary treatment included one or more of radiation therapy, chemotherapy, or surgery. Participation in this study was offered to ever smokers (defined as having smoked at least 100 cigarettes in their lifetime), and involved completing a questionnaire that assessed baseline smoking related behaviours, including nicotine dependence using the Fagerstrom Test for Nicotine Dependence (FTND), and intention to quit smoking. Patients were asked for consent to provide a saliva sample for genetic analyses and for future contact to assess smoking cessation and other health-related outcomes. Personalised counselling about smoking cessation, by trained staff, was also offered. One hundred and eleven consecutive patients have agreed to participate. Most (77 %) are male, with a median age of 65 years (range 36-92 years). Participants reported a median of 37 pack-years of smoking, and 43% were nicotine dependent (FTND score indicating high or very highly dependent). Nicotine dependence level was significantly associated with smoking status at enrolment, with current smokers more likely to report significantly higher nicotine dependence levels than those who were not smoking (p=0.03). While 96% (n=104) of the participants had previously attempted smoking cessation, 35% (n=39) were current smokers at study enrolment. Most of the current smokers (80%) were interested in quitting smoking and in receiving personalized counselling for cessation. This study demonstrates the need to support cessation efforts in this population of cancer patients, and highlights the role of nicotine dependence and smoking behaviour. Future research into smoking cessation methods, including the role of genetic variants in nicotine dependence and cessation, may help us better address smoking behaviours in cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4453. doi:1538-7445.AM2012-4453

Purpose Inter-individual variations in treatment efficacy may be influenced by polymorphisms in DNA repair genes. We investigated the association of 3 functional polymorphisms in the nucleotide excision repair (NER) pathway with survival outcome of 95 patients with metastatic breast cancer (MBC) treated with DNA-damaging chemotherapy.Methods ERCC1 8092 C/A, ERCC2 Asp312Asn and ERCC2 Lys751Gln were determined using Taqman-based genotyping assays. Genotype associations with breast cancer-specific survival (BCSS) and progression-free survival (PFS) were evaluated using Kaplan-Meier estimates and hazard ratios calculated using Cox regression analysis. Tests for trend were conducted by calculating P-values for the HR coefficient in proportional hazards regression models.Results ERCC2 Lys751Gln was significantly associated with BCSS (median: 24.8 months for AA/AC combined and 14.2 months for CC, HR: 1.9 (95% CI 1.06-3.26)). Median BCSS decreased with increasing number of designated adverse genotypes for the 3 polymorphisms (P-trend = 0.003). Risk estimates for PFS were nonsignificantly elevated and were significantly elevated for BCSS for patients with 2 (HR = 2.21, 95% CI: 1.04-4.72) or 3 (HR = 6.67, 95% CI: 2.19-20.29) adverse genotypes. In treatment subgroup analysis, risk estimates for BCSS were significantly elevated for patients with 3 adverse genotypes treated with cyclophosphamide, mitoxantrone and vinblastine (HR: 11.9, 95% CI 1.77-79.51) and P-trend = 0.02 for increasing number of adverse genotypes. Risk of progression was significantly increased for patients with 1 adverse genotype treated with cyclophosphamide, mitoxantrone and carboplatin (HR: 3.5, 95% CI 1.19-10.6) and P-trend = 0.02 for increasing number of adverse genotypes.Conclusion Polymorphisms in NER pathway may impact survival outcome for patients with MBC following treatment with DNA-damaging chemotherapy. These results provide support for a polygenic pathway approach for assessing the prognostic and predictive potential of polymorphisms in treatment outcome.

INTRODUCTION The development of nicotine dependence (ND) is an important final step in the development of nicotine addiction, is associated with substantial morbidity and mortality, and makes long-term smoking cessation difficult. METHODS We used questionnaire data and DNA from buccal swabs previously collected from a population-based case-control study in Northeastern Ontario, Canada; an area with high smoking and smoking-related disease rates. Women smokers were classified into heavy and light phenotypes, a proxy for ND, and we assessed the association between phenotype and single nucleotide polymorphisms (SNPs) that have been associated with increased or decreased risk of ND. RESULTS Women with the variant AA genotype of CHRNA5 rs16969968 or variant CC genotype of LOC123688 rs8034191 were at significantly increased risk of heavy smoking, with age-adjusted odds ratios (ORs) of 3.2 (95% CI: 1.05-10.0) and 2.8 (95% CI: 1.00-7.91), respectively. Women with the variant AA genotype of CHRNA3 rs578775 were at significantly decreased risk of heavy smoking, with an age-adjusted OR of 0.3 (95% CI: 0.12-0.90). CONCLUSION SNPs from 2 distinct variant groups were significantly associated with heaviness of smoking in this homogeneous population of women with high smoking rates, and this study supports the interpretation that there are different mechanisms of nicotine addiction involving both increasing and decreasing risk.

Smoking is a leading cause of premature death and is a risk factor for many serious diseases. Recent studies suggest that the nicotinic acetylcholine receptor gene region of CHRNA5-CHRNA3-CHRNB4 on chromosome 15 is associated with nicotine dependence (ND). Single nucleotide polymorphisms (SNPs) in this region may be associated with heaviness of smoking, a strong predictor of nicotine dependence. This study investigated the association of SNPs in two nicotinic acetylcholine receptor genes, CHRNA5 rs16969968 and CHRNA3 rs578776, with heaviness of smoking in primarily caucasian women in Northeastern Ontario, Canada. This study used previously collected data from a population-based case-control study designed to assess smoking and breast cancer risk in 347 women with breast cancer and 775 population-based controls using a mailed study package with questionnaire and buccal swab. The smoking phenotype, heaviness of smoking, was defined based on available self-reported questionnaire data. The 617 ever-active smoking women (who smoked at least 100 cigarettes) were refined into “heavy” or “light” smokers; heavy smokers (n=200) reported smoking 20 or more cigarettes per day (CPD) for 5 or more years; light smokers (n=71) reported smoking less than 5 CPD for one or more years. Genotyping assays and the ABI 7900 Sequence Detection System (Applied Biosystems, CA) defined SNPs. Odds Ratios (OR) and 95% Confidence Intervals (CI)s were estimated using logistic regression. Women with the homozygous variant genotype AA for CHRNA5 rs16969968 were at significantly increased risk of heavy smoking, with an age-adjusted OR of 3.2 (95% CI 1.05-10.00) in the codominant model; risks increased in a model additionally adjusted for education level and alcohol intake, with an OR of 3.9 (95% CI 1.21-12.32). Women with the homozygous variant genotype TT for CHRNA3 rs578776 were at significantly decreased risk of heavy smoking, with an age-adjusted OR of 0.33 (95% CI 0.12-0.90) and similar risk for the additionally adjusted model. The SNPs were in high linkage disequilibrium (D’ 1.0) with low correlation (r2=0.2) between the risk and protective SNPs suggesting independent associations. When assessing the combined influence of both SNPs, women with the CHRNA5 rs16969968 GG genotype and the CHRNA3 rs578776 TT genotype had the lowest risk of heavy smoking with an age-adjusted OR of 0.57 (95% CI 0.18-1.79). The AA high risk homozygous genotype for CHRNA5 rs16969968 only occurred in association with the CC genotype of CHRNA3 rs578776 and was associated with the highest risk, with an age-adjusted OR of 3.23 (0.90-11.62) and additionally adjusted OR of 3.85 (1.03-14.47). In conclusion, there was a significant positive association of the CHRNA5 rs16969968 and significant negative association of CHRNA3 rs578776 with heaviness of smoking in a population of women in Northeastern Ontario, Canada. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2756. doi:10.1158/1538-7445.AM2011-2756

Background: The relationship between smoking and breast cancer remains controversial. The study aim was to assess the relationship of passive and active smoking to breast cancer risk by N-acetyltransferase 2 (NAT2) phenotype, using a comprehensive assessment of both passive and active smoking. Methods: We undertook a population-based case–control study in Northeastern Ontario, Canada of 347 women diagnosed (2002–2004) with breast cancer and 775 population-based controls. The mailed study package included a questionnaire requesting information about established breast cancer risk factors, passive and active smoking, and a buccal swab for genetic analyses. Results: Among never-active smokers, a long duration of passive smoking was associated with an increased risk of breast cancer (odds ratio (OR) 1.86 (95% confidence interval (95% CI) 1.01–3.44) (test for trend (p = 0.07)); that risk was more elevated for NAT2 slow acetylators (OR 2.76, 95% CI 1.16–6.59) (and highest in extremely slow acetylators), but not elevated for NAT2 fast acetylators (OR 1.17, 95% CI 0.42–3.23). Among active smokers more than 20 pack-years of smoking was associated with an OR of 1.34 (95% CI 0.92-1.96); more elevated among NAT2 fast acetylators OR 1.93 (95% CI 1.01–3.69) but not elevated among NAT2 slow acetylators. Women who were NAT2 fast acetylators in the highest quartile for duration of active smoking had an OR of 2.74 (95% CI 1.42–5.27), with a significant test of trend (p = 0.005). Conclusions: These findings suggest that passive and active smoking may be related to breast cancer, and the effect may be differentially modified by NAT2 phenotype. Further research into the genetic modification of a breast cancer–smoking relationship may help to reconcile earlier discrepant findings.

Abstract The nucleotide excision repair (NER) pathway is important in the repair of bulky DNA lesions, including those that may be induced by cigarette smoking. Excision Repair Cross-Complementing Rodent Repair Deficiency, Complementation Group 2 (ERCC2) is an important gene in the NER pathway. Previous research suggests that polymorphisms in this gene may be associated with altered DNA repair capacity, cancer risk and treatment outcome. This study investigated whether two common single nucleotide polymorphisms (SNPs) in ERCC2 (ERCC2 Asp312Gln and ERCC2 Lys751Gln) were associated with risk of breast cancer, or modified a breast cancer risk associated with smoking. We used data previously collected from a primarily Caucasian population in northeastern Ontario Canada of 347 women diagnosed (2002-2004) with breast cancer and 775 population-based controls. The mailed study package contained a questionnaire that provided information on known breast cancer risk factors and lifetime residential and occupational history of exposure to passive and active smoking, and a buccal swab for genetic analyses. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, and used a refined referent group that excluded women with substantial exposure to passive smoke and who were never active smokers. Both SNPs were in Hardy-Weinburg Equilibrium (HWE) in controls. Overall, there was no significant association with either SNP and risk of breast cancer. Women who were active smokers of long duration (> 29 years), or high (>20) pack-years, were at significantly increased risk of breast cancer if they carried the G allele of ERCC2Asp312Gln, with ORs of 1.72 (95% CI 1.10-2.68) and 1.68 (95% CI 1.09-2.61) and p=0.03 and 0.007 for trend, respectively. Similar significantly increased risks were observed in women who carried the A allele of ERCC2 Lys751Gln, with ORs of 1.77 (95% CI 1.14-2.76) and 1.67 (95% CI 1.08-2.58) and p=0.02 and 0.01 for trend, respectively. In conclusion, our data suggest that polymorphisms in the NER pathway may modify a smoking-breast cancer relationship. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1865.

On their first visit to the Regional Cancer Program, all patients are provided with the "Information for Patients and Families" binder that was designed by an interdisciplinary cancer patient education team. Patients were asked to complete a survey to evaluate the usefulness of this binder. Timely delivery of the "Information for Patients and Families" binder validates a higher level of satisfaction with oncology services because patients are better informed and this translates into a reduction of psychosocial problems. As a result of this study, a decision was made to provide the binder earlier in the patient's journey (e.g., post surgery for thoracic and brain tumor patients).