Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.

As the relation between reproductive factors and breast cancer risk has not been systematically studied in indigenous women of subSaharan Africa, we examined this in a case -control study in Nigeria. In-person interviews were conducted using structured questionnaires to collect detailed reproductive history in 819 breast cancer cases and 569 community controls between 1998 and 2006. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with menarcheal age o17 years, the adjusted OR for women with menarcheal age X17 years was 0.72 (95% CI: 0.54 -0.95, P ¼ 0.02). Parity was negatively associated with risk (P-trend ¼ 0.02) but age at first live birth was not significant (P ¼ 0.16). Importantly, breast cancer risk decreased by 7% for every 12 months of breastfeeding (P-trend ¼ 0.005). It is worth noting that the distribution of reproductive risk factors changed significantly from early to late birth cohorts in the direction of increasing breast cancer incidence. Our findings also highlight the heterogeneity of breast cancer aetiology across populations, and indicate the need for further studies among indigenous sub-Saharan women.

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Previous studies have shown that weight is inversely associated with premenopausal breast cancer and positively associated with postmenopausal disease. Height has been shown to be positively correlated with breast cancer risk, but the association was not conclusive for premenopausal women. These previous studies were conducted primarily in Western countries, where height is not limited by nutritional status during childhood. The authors assessed the association between breast cancer and anthropometric measures in the Nigerian Breast Cancer Study (Ibadan, Nigeria). Between 1998 and 2009, 1,233 invasive breast cancer cases and 1,101 controls were recruited. The multivariate-adjusted odds ratio for the highest quartile group of height relative to the lowest was 2.03 (95% confidence interval (CI): 1.51, 2.72; P-trend < 0.001), with an odds ratio of 1.22 (95% CI: 1.14, 1.32) for each 5-cm increase, with no difference by menopausal status. Comparing women with a body mass index in the lowest quartile group, the adjusted odds ratio for women in the highest quartile category was 0.72 (95% CI: 0.54, 0.94; P-trend = 0.009) for premenopausal and postmenopausal women. Influence of height on breast cancer risk was quite strong in this cohort of indigenous Africans, which suggests that energy intake during childhood may be important in breast cancer development.