Walter C. Willett, MD, Dr.PH

Much evidence indicates that risk factors for breast cancer can act during multiple periods over the life course. Laboratory experiments and observational studies strongly suggest that childhood, adolescence and early adulthood are critical periods in the pathogenesis of breast cancer. This may possibly be due to the rapid division of undifferentiated cells between puberty and first birth.

While it is critically important to examine specific exposures during these life stages in relation to subsequent breast cancer risk, accomplishing this objective has been difficult for many reasons. Challenges include the long time interval until breast cancer develops when following women prospectively until disease occurs in some portion of the population. It is also difficult to accurately recall childhood and early adult diet and lifestyle exposures in midlife and later when breast cancer is typically diagnosed. These issues have been the reason for the development of the Growing-Up Today Study (GUTS), the Nurses' Health Study II (NHS-II) the Pooling of Prospective Studies of Diet and Cancer (referred to as the Pooling Project) and now, the Nurses' Health Study III, all of which have been partially supported by BCRF.

In the work led by Dr. Willett, the NHSIII questionnaires are now completely web-based and readily allow branched questions and individually timed data collection. Thus, Dr. Willett's team is collecting data on diet and lifestyle while NHS3 participants are pregnant, which will provide unique data that can be used to study cancer incidence several generations into the future. In the case of NHSII, to expand the scope of life course exposures, the investigators have collected detailed data on diet and physical activity during high school, as reported by participants while they were still young adults, and on exposures in utero and early childhood, as reported by the participants' mothers. These resources allow the examination of hypotheses that diet, physical activity, and other lifestyle factors operate from in utero and childhood and throughout adult life to modulate cancer risk. These are likely mediated in part by hormonal and metabolic factors and interact with genetic susceptibilities.

Also, the GUTS cohort has so far gathered information from pre-puberty through young adulthood, while the Pooling Project has combined breast cancer and lifestyle data from 18 female cohorts around the world. Examination of these factors in different age, racial and ethnic groups, will enhance the understanding of the etiology of breast cancer.

Mid-year Progress: Dr. Willett's team is continuing their follow-up and analyses related to diet and lifestyle in adolescence and early adulthood, critical periods in the pathogenesis of breast cancer. They are also examining risk of breast cancer in relation to anthropometric measurements of adult women from over 20 cohort studies around the world. These studies have been carried out in the Growing-Up Today Study (GUTS) and the Pooling of Prospective Studies of Diet and Cancer (Pooling Project) with support from BCRF.

In the Pooling Project, Dr. Willett and his team have found positive relationships between body mass index, other measurements and breast cancer risk overall and by estrogen receptor status. They have begun recruiting participants into a new online cohort, the Nurses' Health Study 3 (NHS3). This cohort of young, ethnically diverse women will serve as a future resource to examine the role of exposures during adolescence and early adulthood on the pathogenesis of breast cancer. The researchers have expanded the eligibility of participants in NHS3 to include LPNs/LVNs since the representation of minority women is substantially greater in the latter group and breast cancer etiology in minorities is critical to understand. They are currently moving forward on their goal of increasing minority women's participation by using several recruitment strategies including the newly developed Ambassador program to assist with the recruitment and increase enrollment in the NHS3. Dr. Willett's team have identified a group of "super participants" from NHSII and NHS3 who are enthusiastic, respond to first requests for questionnaire completion, and are eager to encourage others to consider participating in the new online cohort.

Bio:
Dr. Walter Willett is Professor of Epidemiology and Nutrition and Chairman of the Department of Nutrition at Harvard School of Public Health and Professor of Medicine at Harvard Medical School. Dr. Willett, an American, was born in Hart, Michigan and grew up in Madison, Wisconsin, studied food science at Michigan State University, and graduated from the University of Michigan Medical School before obtaining a Doctorate in Public Health from Harvard School of Public Health. Dr. Willett has focused much of his work over the last 30 years on the development of methods, using both questionnaire and biochemical approaches, to study the effects of diet on the occurrence of major diseases. He has applied these methods starting in 1980 in the Nurses' Health Studies I and II and the Health Professionals Follow-up Study. Together, these cohorts that include nearly 300,000 men and women with repeated dietary assessments are providing the most detailed information on the long-term health consequences of food choices.

Dr. Willett has published over 1,500 articles, primarily on lifestyle risk factors for heart disease and cancer, and has written the textbook, Nutritional Epidemiology, published by Oxford University Press. He also has three books book for the general public, Eat, Drink and Be Healthy: The Harvard Medical School Guide to Healthy Eating, which has appeared on most major bestseller lists, Eat, Drink, and Weigh Less, co-authored with Mollie Katzen, and most recently, The Fertility Diet, co-authored with Jorge Chavarro and Pat Skerrett. Dr. Willett is the most cited nutritionist internationally and is among the five most cited persons in all fields of clinical science. He is a member of the Institute of Medicine of the National Academy of Sciences and the recipient of many national and international awards for his research.