Associations between Smoking and Alcohol and Follicular Lymphoma Incidence and Survival: A Family-Based Case-Control Study in Australia

SIMPLE SUMMARY: Previous studies on the relationship between smoking and follicular lymphoma (FL) incidence and survival are inconsistent, while the evidence regarding alcohol intake appears to support an inverse association. In this population-based family case-control study, we observed a positive association between multiple measures of personal smoking history and increased risk of FL, including evidence of a dose-response. We also observed an association between personal smoking and poorer overall survival after FL diagnosis and an indication that personal smoking may be associated with poorer FL-specific survival. Additionally, among non-smokers, we found increased FL risk for those exposed indoors to more than two smokers during their childhood. In contrast, we observed no evidence of an association between recent alcohol consumption and risk of FL, overall survival, or FL-specific survival. Our findings further strengthen the evidence for ongoing multi-faceted tobacco control activities to reduce FL incidence and improve patient outcomes. ABSTRACT: The association between smoking and alcohol consumption and follicular lymphoma (FL) incidence and clinical outcome is uncertain. We conducted a population-based family case-control study (709 cases: 490 controls) in Australia. We assessed lifetime history of smoking and recent alcohol consumption and followed-up cases (median = 83 months). We examined associations with FL risk using unconditional logistic regression and with all-cause and FL-specific mortality of cases using Cox regression. FL risk was associated with ever smoking (OR = 1.38, 95%CI = 1.08–1.74), former smoking (OR = 1.36, 95%CI = 1.05–1.77), smoking initiation before age 17 (OR = 1.47, 95%CI = 1.06–2.05), the highest categories of cigarettes smoked per day (OR = 1.44, 95%CI = 1.04–2.01), smoking duration (OR = 1.53, 95%CI = 1.07–2.18) and pack-years (OR = 1.56, 95%CI = 1.10–2.22). For never smokers, FL risk increased for those exposed indoors to >2 smokers during childhood (OR = 1.84, 95%CI = 1.11–3.04). For cases, current smoking and the highest categories of smoking duration and lifetime cigarette exposure were associated with elevated all-cause mortality. The hazard ratio for current smoking and FL-specific mortality was 2.97 (95%CI = 0.91–9.72). We found no association between recent alcohol consumption and FL risk, all-cause or FL-specific mortality. Our study showed consistent evidence of an association between smoking and increased FL risk and possibly also FL-specific mortality. Strengthening anti-smoking policies and interventions may reduce the population burden of FL.