The Hygiene Hypothesis and Breast Cancer Risk

Institution: Cancer Prevention Institute of California
Investigator(s): Christina Clarke Dur, Ph.D. -
Award Cycle: 2003 (Cycle IX) Grant #: 9KB-0019 Award: $366,955
Award Type: New Investigator Awards
Research Priorities
Etiology and Prevention>Etiology: the role of environment and lifestyle



Initial Award Abstract (2003)
New ideas for breast cancer causes should be consistent with patterns of breast cancer occurrence: how it has increased over time and how it varies by country, race/ethnicity, and socioeconomic group. A new group of exposures meeting these requirements are microbial ("germ") exposures, which have been studied previously as part of the "hygiene hypothesis" to explain the causes of allergic and autoimmune diseases, but have never been investigated for breast cancer. This idea holds that reduced or delayed exposures to microbes, or living in a mostly disease-free, sanitized environment hampers development of a healthy immune system. An underdeveloped immune response might subsequently influence breast cancer development by weakening immune responses against tumors, increasing estrogen production, or both. Some of the impetus for this research comes from hearing breast cancer survivors say: "I've never been sick a day in my life, and now I get breast cancer!"

We want to learn whether women with breast cancer are less likely than healthy women to have a history of certain exposures known to positively influence healthy immune system development. Examples of these exposures, which we have termed "immuno-developmental exposures", include many characteristic events of childhood, including residence on a farm or near animal pens, pet ownership, exposure to siblings, playmates or other children through nursery school or day care; as well as history and age at development of selected infectious diseases, history of vaccinations, and others.

This study will take advantage of a large Bay Area breast cancer study that enrolled white, African American and Hispanic breast cancer patients (cases) and women without breast cancer (controls). These women have been interviewed previously about established breast cancer risk factors like reproductive characteristics, alcohol use and other topics. We will re-contact a selection of these women, about 527 cases and 557 controls, to ask them by telephone about exposures relevant to the hygiene hypothesis for immune system development. We will then use statistical analysis of their responses to determine if cases have a different profile of immuno-developmental exposures than controls. We will pay special attention to ruling out apparent associations that actually may be due to established risk factors more common in women with these exposures than without.

This study takes an idea that has been well-studied for allergies and autoimmune disease and applies it for the first time to breast cancer, which has enough similarities to the other diseases to make the idea reasonable. As so much information about established risk factors has already been collected from the study subjects, we can conduct a cost-effective study of the new ideas but also rule out overlapping effects of established factors. We will work to develop questionnaire concepts and wording so that older women and women from diverse cultural backgrounds can easily understand the questions. The study team is headed by a young investigator with a strong interest in breast cancer and in pursuing these and other ideas about immunologic risk factors for breast cancer in the future.


Final Report (2008)
New ideas for breast cancer causes should be consistent with patterns of breast cancer occurrence: how it has increased over time and how it varies by country, race/ethnicity, and socioeconomic group. Meeting these requirements are microbial exposures, which have been studied previously as part of the “hygiene hypothesis” to explain the causes of allergic and autoimmune diseases, but have never been investigated for breast cancer. This idea holds that reduced or delayed exposures to microbes, or living in a mostly disease-free, sanitized environment hampers development of a healthy immune system. An underdeveloped immune response might subsequently influence breast cancer development by weakening immune responses against tumors, increasing estrogen production, or both. In this study, we sought to learn whether women with breast cancer were less likely than healthy women to report certain exposures known to positively influence healthy immune system development. This study met all of its original aims: 1) to develop a new, structured questionnaire to capture these concepts reliably and suitably for older women of diverse ethnic backgrounds; 2) Re-contact and interview women who recently participated in a large, San Francisco Bay Area population-based case-control study of breast cancer, and 3) after combining this new information with that previously collected about established risk factors, conduct statistical analyses to explore associations of immunodevelopmental factors with breast cancer risk. This study accomplished several important goals xxx.

Progress towards specific aims: Interviewing of study subjects commenced in late April 2004. As of June 1, 2006, 949 subjects have been located and successfully interviewed. One barrier that could not be overcome were higher than expected numbers of subjects who explicitly refused participation (n=xxx), or who moved and were not locatable (n=xxx).

Future directions: Preliminary analyses indicated an interesting association of history of mastitis with increased risk of postmenopausal breast cancer. We will investigate this association further using the larger California Teachers Study cohort resource.

Impact: This study took an idea that has been well-studied for allergies and autoimmune disease and applied it for the first time to breast cancer, which has enough similarities to the other diseases to make the idea reasonable. This research should help to jumpstart new efforts to study the role of immune system factors in causing breast cancer. A finding that immuno-developmental exposures partly explain socioeconomic and racial/ethnic differences in breast cancer incidence could thereby provide a new way to understand and address these disparities. Ultimately, if immuno-developmental exposures are found to be causal for breast cancer, feasible primary prevention efforts could be developed to strengthen the immune response, perhaps through vaccination with harmless surrogates of important microbial exposures.