The prevalence of Vitamin D inadequacy is high worldwide but particularly elevated among women living in Karachi, Pakistan, even though the city is located at a high latitude with year-round adequate concentrations of UVB radiation. Sun exposure is the major source of Vitamin D, but due to multiple factors in the predominately Muslim population and modern lifestyle behaviors, Vitamin D deficiency is becoming a major public health problem. There are new data emerging that highlight the potential protective effect of Vitamin D for breast cancer, but evidence varies between different studies. Therefore, we undertook this study with the overall aim to evaluate the role of Vitamin D in breast cancer among Pakistani women. To meet these objectives, this case control study was conducted in two hospitals of Karachi, Pakistan: Aga Khan University Hospital (AKUH) and Karachi Institute of Radiation and Nuclear Medicine Hospital (KIRAN) during 2015-2017. Breast cancer cases had newly diagnosed histologically confirmed primary breast cancer. Controls were women free of breast or any other cancer were matched by age (year of birth + 5 years), residence in the same geographic area and study site from surgery, family medicine and oncology clinics of AKUH & KIRAN. An interviewer-administered detailed questionnaire was used, and venous blood was collected to measure serum Vitamin D level at the end of interview. The detailed questionnaire provided the opportunity to explore several factors related to breast cancer in this cohort. The objectives of the present study were: 1) To determine the association of Vitamin D (serum Vitamin D (25-hydroxyVitamin D) level, Vitamin D supplementation and sun exposure with breast cancer among Pakistani women, 2) To identify other risk factors associated with breast cancer among Pakistani women, 3) To evaluate the risk factors associated with triple negative breast cancer TNBC and non TNBC subtypes (including hormone receptor status and stage of diagnosis), 4) To evaluate the association of diet with BC among Pakistani women using the modified AHEI 2010 and its component scores 5) to assess patient delay in breast cancer diagnosis, its associated factors and stage of diagnosis among breast cancer patients in Karachi, Pakistan. Main study findings were that Vitamin D deficiency was significantly associated with increased risk of breast cancer, and intake of Vitamin D supplements was associated with decreased risk of breast cancer, supporting the hypothesis that Vitamin D may play a protective role against breast cancer. Other factors associated with increased breast cancer risk were poor socioeconomic status, poor education and lack of employment status. There was no association of any of the reproductive factors or familial risk factors with breast cancer and it is likely that environmental and lifestyle factors related to poor socioeconomic status had a major role in breast cancer etiology. There was an association of an even higher risk of the triple negative breast cancer subtype than non-triple negative breast cancer subtype, among women with both Vitamin D deficiency and poor socioeconomic status. Based on these findings’ correction of Vitamin D deficiency in women is a reasonable and cost effective strategy to reduce the incidence of all subtypes of breast cancer and triple negative breast cancer like aggressive breast cancer in particular. Such an approach should be carefully interpreted and further confirmed by large prospective studies or clinical trials. In another sub study, high intake of grains, both whole and refined, was also significantly associated with a higher risk of breast cancer in Pakistani women. Limiting refined carbohydrate intake might be a beneficial public health message as it may represent a potentially modifiable risk factor for breast cancer in our population but requires additional in-depth study. Breast cancer diagnosis delay study reported that despite noticing a breast lump, 64.9% of women diagnosed with breast cancer delayed medical consultation by a median of 7 months. The recommendation from this study is to provide better education to women about breast cancer awareness, and methods of self-examination and what are the most likely signs of breast cancer. In conclusion, Pakistan is a low-income group country with fifty percent of women below the poverty line. Breast cancer rates and mortality are particularly high among poor women. This study identifies several inexpensive strategies and approaches that if implemented may help reduce the incidence, delay in breast cancer diagnosis and morbidity of breast cancer in Pakistani women.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201
