| Various exposures have been investigated by epidemiologic studies as risk factors for leukemia incidence, however studies focusing on and therefore findings particular to Small Lymphocytic Lymphoma (SLL) and Chronic Lymphocytic Leukemia (CLL) have been sparse. In fact, according to the NCI, there are only a few established risk factors for CLL/SLL: 1) being middle-aged or older, male, or white; 2) a family history of CLL or cancer of the lymph system; and 3) having relatives who are Russian Jews or Eastern European Jews. As none of these are risk factors that can be altered with lifestyle changes, we sought to explore potential and likely risk factors that can be modified with behavior.;Using the Women's Health Initiative (WHI) and applying an age and race matched, nested, 1:4 case-control design, we investigated CLL/SLL risk in postmenopausal women with three specific aims of interest: personal habits, comprising diet, drinking habits (including alcohol and coffee, both which have potential biological activity in leukemogenesis), and exercise; hormonal exposures, such as oral contraceptives (OC) and hormone therapies (HT); and pesticide exposures. These areas were chosen because there is a great need to understand 1) why CLL/SLL is significantly more prevalent in industrial countries compared to developing countries, and 2) why men have a two-fold increase in their risk of developing CLL/SLL.;Women enrolled on WHI clinical trials who consumed coffee on a regular basis had lower risk of CLL/SLL (odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.51, 1.05; P=.09), compared to non-coffee drinkers. Past oral contraceptive use (OR=0.74, 95% CI: 0.56, 0.96; P=.03) and obesity (OR=0.71, 95% CI: 0.53, 0.94; P=.20) both showed to be protective against CLL/SLL, whereas past estrogen use (OR=1.32, 95% CI:1.02, 1.71; P=.04) increased the risk. We did not find any significant associations with other personal habits and CLL/SLL risk, such as alcohol use, dietary factors, or exercise habits. Also, past OC users had lower CLL/SLL risk than women with no past OC exposure (OR= 0.73, 95% CI: 0.56, 0.96; P=.02). Past HT use---specifically estrogen-alone therapy---however, conferred higher CLL/SLL risk (OR = 1.32, 95% CI: 1.01, 1.71; P=.04). In addition, any pesticide exposure during adulthood, resulted in significantly higher risk for developing CLL/SLL compared to no pesticide exposure (OR= 1.65, 95% CI: 1.11, 2.45; P=.01).;Overall, we can conclude that risk factors which matter the most for CLL/SLL risk, such as coffee drinking, obesity, and OC use, all have estrogenic effects which in this case appear to offer protection. The biological mechanisms leading to these findings would needs further investigation. Although certain pesticides also alter estrogen in the body, the main impact of pesticides of our study is most likely due to various carcinogens causing DNA damage.;Our findings identified risk factors specific to industrialized countries helping explain the higher CLL/SLL incidence in these countries, compared to developing countries. In addition, we showed a probable association of estrogen dominance being protective against CLL/SLL, a plausible explanation lower rates of this hematological cancer in women relative to men. |
