Dr. Rajini Nagrani

Enrollment number : HLTH09200904001
Date of Enrolment in HBNI : 1st September 2009
Date of Submission of Thesis : 24th June 2014
Title of the Thesis : Risk factors of Breast Cancer in Rural & Urban India


Abstract :
Introduction : It has been observed for long time that the rates of BC differ in rural and urban areas. However, there are very few studies in literature to address the reasons for the differences in BC rates of rural and urban area.

Methodology : A hospital based case-control (female visitors) study was conducted at Tata Memorial Hospital, Mumbai during the period of January 2009 to September 2013 with information collected on residential status, reproductive history and anthropometric measurements. ER, PR and Human Epidermal Growth Factor Receptor 2 (HER2) status were obtained from hospital pathology records. 10ml blood sample was collected from each study participant and centrifuged into plasma and buffy coat. DNA extracted from buffy coat were then genotyped for 384 SNPs in Illumina Hi-Scan

Results & Discussion : A total of 1637 cases and 1515 controls were enrolled in the study.A statistically significant protection in risk of BC was observed in women who lived for first twenty years of life in rural area as compared to women who lived less than 20 years in rural area, as exposures in early life may be more important in the development of BC compared to current exposures. The risk of BC significantly increased with every 2 year delay in pregnancy after age 25 in women from both urban and rural areas. On stratifying into menopausal status, statistically significant association was observed only in premenopausal women, while the postmenopausal women showed increase but statistically non significant risk. This is possibly because of homogeneity of population in relation to age at first pregnancy in older cohort where the median age at first child birth is lower as compared to the women from newer cohort. The current OC users using OC for more than 2 years showed increased risk for urban women compared to women without use of OC (OR = 2.46; 95% CI: 0.99–6.12). The association may be interpreted as causal in urban India. As the association was significant only for current users, it can be interpreted that OC may act as late-stage promoters.

A protective association observed in premenopausal women (OR = 0.93; 95% CI: 0.91–0.95) with per unit increase in BMI (world) continued in women who had attained menopause less than 10 years ago (OR = 0.95; 95% CI: 0.92–0.98). No increase in risk in postmenopausal BC could be observed possibly because of carry-over protective effect.A strong significant increase (OR =1.85;P = 0.03) with dose-response was observed for women with high BMI who attained menopause ≥ 10 years ago from the date of enrolment. With every 0.1 increase in WHR the risk of BC increased (OR = 1.76; 95% CI: 1.55–2.01), (OR = 1.55; 95% CI: 1.29–1.86) (OR = 1.69; 95% CI: 1.47–1.96) and (OR = 1.71; 95% CI: 1.41–2.00) in urban, rural, premenopausal and postmenopausal women respectively.In the present study the prevalence of WHR was higher in women residing in urban as well as rural areas. Even with women for normal BMI, 34.4% had higher WHR in the present study. This is consistent with thin-fat hypothesis of Asian –Indians.

The present study could replicate 7 SNPs from BC GWAS. Five SNPs were successfully replicated out of 42 Candidate SNPs of BC used for analysis. SNPs selected from FGFR2 gene were positively associated with BC.

Conclusion : The current study demonstrates that protection observed for BC by living in a rural area is possibly because of less prevalence of risk factors viz. late age at first full-term pregnancy, OC use and tallness. The central obesity common to both rural and urban is a strong risk factor for BC. The study was successful in identifying new SNPs in obesity genes identified using Bioinformatics tool, however their association would have to be replicated in other studies particularly because they were not significant after adjusting for multiple comparisons. This also indicates that the lifestyle factors are more important than the genetic markers from public health point of view.