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Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34-0.91; P=.02) or K (OR 0.52; 95% CI 0.30-0.90; P=.02) demonstrated a significant decrease in risk of PD versus individuals carrying the most common haplogroup, H. Furthermore, a specific SNP that defines these two haplogroups, 10398G, is strongly associated with this protective effect (OR 0.53; 95% CI 0.39-0.73; P=.0001). SNP 10398G causes a nonconservative amino acid change from threonine to alanine within the NADH dehydrogenase 3 (ND3) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men (OR 0.43; 95% CI 0.27-0.71; P=.0009). In addition, SNP 9055A of ATP6 demonstrated a protective effect for women (OR 0.45; 95% CI 0.22-0.93; P=.03). Our results suggest that ND3 is an important factor in PD susceptibility among white individuals and could help explain the role of complex I in PD expression.

Objective: To assess the relation between whole and refined grain intake and risk of incident postmenopausal breast cancer. Findings from case-control studies of whole and refined grain intake and risk of postmenopausal breast cancer have been inconclusive., Methods: The Iowa Women's Health Study is a prospective cohort study of women initially 55-69 years old that relates diet and other lifestyle factors to cancer risk. After exclusions a total of 29,119 menopausal women who answered a 1986 baseline and a 1989 follow-up questionnaire were followed for 9 years for incident breast cancer., Results: Compared to women who at baseline rarely ate whole grain foods, women who habitually ate whole grain had a healthier lifestyle, including a higher likelihood of prior screening mammography. The multivariate-adjusted risk of incident breast cancer was 20% higher in women in the highest quintile of whole grain intake, compared to women in the lowest quintile of whole grain intake (95% confidence interval 0.95-1.5; p-value for trend = 0.03). No increase in breast cancer risk was found in women who had not undergone screening mammography before 1989; the apparent increase in risk was therefore likely due to increased use of screening mammography. Refined grain intake was not associated with breast cancer risk., Conclusion: Consistent with inverse but not statistically significant associations between whole grain intake and breast cancer in case-control studies, both whole and refined grain intakes are unrelated to risk of postmenopausal breast cancer in these Iowa women.