<i>TP53</i> Mutation Spectrum in Lung Cancer Is Not Different in Women and Men

Marrogi, Aizen J.; Mechanic, Leah E.; Welsh, Judith A.; Bowman, Elise D.; Khan, Mohammed A.; Enewold, Lindsey; Shields, Peter G.; Harris, Curtis C.

doi:10.1158/1055-9965.epi-04-0640

Cited by 14 publications

(10 citation statements)

References 13 publications

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“…Fourteen polymorphisms in TP53 were genotyped in two study populations, an ongoing case-control study (25,26) and a case-only study described previously (24,34). No variation was observed for TP53_25 (Ex11 +567, G>A) or TP53_64 (Ex6 À24, G>A) in our case-control or case-only study (data not shown).…”

Section: Resultsmentioning

confidence: 61%

Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors

Mechanic

Bowman

Welsh

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Lung cancer is primarily caused by tobacco smoking, but susceptibility is likely modified by common genetic variation. In response to many forms of cellular stress, including DNA damage, the p53 protein functions to induce cell cycle arrest, DNA repair, senescence, or apoptosis. We hypothesized that common TP53 haplotypes modulate pathways of lung carcinogenesis and lung cancer susceptibility or prognosis. To investigate our hypothesis, 14 polymorphisms in TP53, including haplotype tagging and coding single nucleotide polymorphisms, were genotyped in two studies from the greater Baltimore, Maryland area. One study is a case-control study and the second is a case-only study for which TP53 mutational spectra data are available. African Americans with Pro-T-A-G-G haplotypes of the combined TP53 polymorphisms TP53_01 (rs1042522), TP53_65 (rs9895829), TP53_66 (rs2909430), TP53_16 (rs1625895), and TP53_11 (rs12951053) had both an increased risk for lung cancer (odds ratio, 2.32; 95% confidence interval, 1.18-4.57) and a worsened lung cancer prognosis (hazards ratio, 2.38; 95% confidence interval, 1.38-4.10) compared with those with Arg-T-A-G-T haplotypes. No associations of TP53 polymorphisms with lung cancer were observed in Caucasians. In the case-only study, several polymorphisms in TP53 and TP53 haplotypes, overlapping regions of TP53 associated with risk and prognosis in African Americans, were associated with increased odds of somatic TP53 mutation in lung tumors in Caucasians. In conclusion, common genetic variation in TP53 could modulate lung cancer pathways, as suggested by the association with lung cancer in African Americans and somatic TP53 mutation frequency in lung tumors. (Cancer Epidemiol Biomarkers Prev 2007;16(2):214 -22)

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Section: Resultsmentioning

confidence: 61%

Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors

Mechanic

Bowman

Welsh

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…This suggests that women may be more susceptible to the DNA damaging effects of tobacco smoke than men. Some, 28 31 32 but not all, 33 studies also identified sex differences in the frequency of mutations in tumour suppressor genes, with higher frequencies seen among women than men. Furthermore, it may be that women extract a greater quantity of carcinogens and other toxic agents from the same number of cigarettes than men, which again might explain why smoking confers a greater excess risk in women than in men.…”

Section: Discussionmentioning

confidence: 99%

Do smoking habits differ between women and men in contemporary Western populations? Evidence from half a million people in the UK Biobank study

2014

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ObjectivesSeveral studies have shown that smoking may confer a greater excess risk for chronic diseases in women compared with men. The reasons for this excess risk of smoking in women are unclear, yet sex differences in smoking habits may play a role. We, thus, characterised sex differences in smoking habits in a contemporary Western population.DesignCross-sectional population-based study.SettingUK Biobank Resource.Participants499 797 (54% women) individuals with data on smoking habits.Main outcome measuresWomen-to-men prevalence ratios in smoking status, and the women-minus-men mean difference in age at smoking initiation, number of cigarettes smoked daily and age at smoking cessation in 5-year birth cohort bands.ResultsThe women-to-men ever-smoking ratio ranged from 0.57 in the oldest to 0.87 in the youngest birth cohort. In the oldest cohort, born 1935–1939, women started smoking 1.9 years (95% CI 1.7 to 2.1) later than did men, but in those born after 1959 there was no difference in the age at initiation. The oldest women smoked 5.3 (95% CI 4.7 to 5.9) cigarettes per day fewer than did the oldest men, compared with 2.0 (95% CI 1.7 to 2.3) fewer cigarettes smoked per day in the youngest, born 1965–1969. Among quitters, women born before 1945 were, on average, 1.5 years older than their male contemporaries, but this differential was 1 year or less among people born after 1949.ConclusionsDifferences in smoking behaviour between women and men have decreased over time. Even past differentials are unlikely to explain the increased susceptibility to smoking-related chronic disease in women compared with men that has previously been observed. Future studies are required to determine whether sex differences in the physiological and biological effects of smoking are responsible for the differential impact of smoking on health in women and men.

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“…Sex-specific differences have also been observed for associations between EGFR mutations and the HLA-A2(þ) allele. 24 In addition, p53 transversion mutations 25 and insertion/deletion mutations 26 are more frequent in females. Various carcinogens originated from environmental exposures or endogenous processes constantly threaten DNA integrity.…”

Section: Discussionmentioning

confidence: 99%

EGFR exon 19 in‐frame deletion and polymorphisms of DNA repair genes in never‐smoking female lung adenocarcinoma patients

Yang

et al. 2012

Intl Journal of Cancer

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We explored potential associations between genetic polymorphisms in genes related to DNA repair and detoxification metabolism and epidermal growth factor receptor (EGFR) mutations in a cohort of 410 never-smoking patients with lung adenocarcinoma. Multivariate-adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CI) of EGFR mutation status in association with the genotypes of DNA repair and detoxification metabolism genes were evaluated using logistic regression analysis. We found an association between in-frame deletion in EGFR exon 19 and a single nucleotide

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TP53 Mutation Spectrum in Lung Cancer Is Not Different in Women and Men

Cited by 14 publications

References 13 publications

Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors

Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors

Do smoking habits differ between women and men in contemporary Western populations? Evidence from half a million people in the UK Biobank study

EGFR exon 19 in‐frame deletion and polymorphisms of DNA repair genes in never‐smoking female lung adenocarcinoma patients

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