Associations Between Cigarette Smoking, Lifestyle Factors, and Microsatellite Instability in Colon Tumors

Slattery, Martha L.; Curtin, Karen; Anderson, Kristin E.; Ni, Khe; Ballard, L.; Edwards, Sandra L.; Schaffer, Donna; Potter, John D.; Leppert, M.; Samowitz, Wade S.

doi:10.1093/jnci/92.22.1831

Cited by 303 publications

(263 citation statements)

References 15 publications

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“…In the U.S., two small studies reported microsatellite instability in 16.9% 36 and 19.0% 37 of Latinos. In Puerto Rico, a larger retrospective study investigated an unselected group of Latino patients with CRC, on whom IHC staining of only two MMR proteins (MLH1 and MSH2) was performed 22 .…”

Section: Discussionmentioning

confidence: 99%

“…Some have hypothesized that this finding may reflect differences in environmental and lifestyle factors between Latinos and other populations. For example, MSI-H CRC has been associated with tobacco use 36, 38 , which is less prevalent in Latinos compared to other populations 39 ; and high body-mass-index, which is more common in Latinos, is associated with microsatellite stable CRC tumors 40 . Further studies are needed to investigate these hypotheses.…”

Section: Discussionmentioning

confidence: 99%

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DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer

Ricker

Hanna

Peng

et al. 2017

Cancer

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Background The landscape of hereditary syndromes and clinicopathologic characteristics among U.S. Latinos/Hispanics with colorectal cancer (CRC) remains poorly understood. Methods A total of 265 CRC patients enrolled in the Hispanic Colorectal Cancer Study were included in this study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data was abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. Results The mean age at diagnosis was 53.7 years (SD=10.3), and 48.3% were female. Overall, 21.2% reported a first- or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% met at least one criterion. Of the 161 individuals who had immunohistochemistry (IHC) and/or microsatellite instability (MSI) testing performed, 21 (13.0%) had mismatch repair (MMR) deficient tumors. dMMR tumors were associated with female sex (61.9%), earlier age of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first (23.8%) or second (9.5%) degree family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MLH1=6, MSH2=4, MHS6=2, and PMS2=1). We identified two additional MLH1 mutation carriers by genetic testing who had not received IHC/MSI testing. In total, 5.7% of the entire cohort were confirmed cases of Lynch syndrome. Additionally, six individuals (2.3%) had a polyposis phenotype. Conclusions The proportion of dMMR tumors in Latinos (13%) is similar to estimates in non-Hispanic Whites. The majority of individuals with dMMR tumors were confirmed to have Lynch syndrome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer

Ricker

Hanna

Peng

et al. 2017

Cancer

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“…Initial analyses of the relationships between microsatellite instability determined by either the panel of 10 tetranucleotides, BAT-26 or TGF␤RII in addition to various clinical and molecular features, gave nearly identical results regardless of the way instability was measured. 6 To simplify subsequent analyses we therefore combined these primer sets into a panel of 12 and scored a tumor as unstable if it was unstable with the panel of 10 tetranucleotides (as defined above), BAT-26 or TGF␤RII. Any associations detected in this way were then further defined by considering instability results with each of these 3 measures separately.…”

Section: Msimentioning

confidence: 99%

“…5 In our previous evaluation of lifestyle factors associated with MSI we found that cigarette smoking is specifically associated with MSI tumors, whereas other factors such as physical activity, body size, and use of aspirin and non-steroidal anti-inflammatory drugs appear to be related equally to MSIϩ and MSIϪ tumors. 6 Although dietary factors, to our knowledge, have not been examined with MSI in tumors, it is reasonable to hypothesize that components of diet, especially those that may be influenced by cigarette smoking, could influence development of unstable tumors. Alcohol could lead to unstable tumors independently or in combination with cigarette smoking.…”

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confidence: 99%

Dietary intake and microsatellite instability in colon tumors

et al. 2001

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Microsatellite instability (MSI) occurs in approximately 15% of colon tumors. Other than relatively rare mutations in mismatch repair genes, the causes of MSI are not generally known. The purpose of this study was to determine if dietary intake of nutrients previously reported as being associated with colon cancer relate specifically to the MSI disease pathway. Data from a population-based case-control study of adenocarcinoma of the colon were used to evaluate associations between dietary intake and MSI. Participants were between 30 and 79 years of age at time of diagnosis and included both men and women. Dietary intake data were obtained from a computerized diet history questionnaire. MSI was evaluated in several ways: by a panel of 10 tetranucleotide repeats, and by 2 mononucleotide repeats, BAT-26 and TGF␤RII. A total of 1,510 cases had valid study data and tumor DNA on which we were able to obtain MSI status. Cases with and without MSI were compared with dietary data reported by 2,410 population-based controls to determine dietary associations that may be different for these 2 subsets of cases. We compared dietary intake for cases with and without MSI to further determine associations that are specific to the MSI disease pathway. Key words: colon cancer; diet; microsatellite instability; alcohol; cigarette smokingDiet has been repeatedly implicated in the etiology of colon cancer. 1,2 Inconsistencies in observed associations across studies could stem from individual dietary components being associated with certain types of tumors and disease pathways, but not with colon cancer overall. Ability to examine diet in relationship to specific disease end points, as determined by specific mutations in tumors, should enhance our understanding of the disease process and the role of diet in that process.Microsatellite instability (MSI) occurs in approximately 15% of colon tumors. 3,4 People with inherited mutations of mismatch repair genes develop MSI in colon tumors; causes of MSI in sporadic colon tumors are largely unknown. 5 In our previous evaluation of lifestyle factors associated with MSI we found that cigarette smoking is specifically associated with MSI tumors, whereas other factors such as physical activity, body size, and use of aspirin and non-steroidal anti-inflammatory drugs appear to be related equally to MSIϩ and MSIϪ tumors. 6 Although dietary factors, to our knowledge, have not been examined with MSI in tumors, it is reasonable to hypothesize that components of diet, especially those that may be influenced by cigarette smoking, could influence development of unstable tumors. Alcohol could lead to unstable tumors independently or in combination with cigarette smoking. 7 Dietary antioxidants may decrease risk of unstable tumors through their role in reducing oxygen free radicals generated by cigarette smoke. 8 Other dietary factors hypothesized to influence cell growth and apoptosis, such as calcium, vitamin D and glycemic index, could be hypothesized as being associated with MSI in tumors. 9 In this ...

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“…Perhaps more important, another 10 -15% of sporadic colorectal carcinoma cases are reportedly caused by the epigenetic silencing of the hMLH1 gene. Inappropriate silencing of the hMLH1 gene occurs through an incompletely understood mechanism in colonic tissues, appears to be influenced by age and, possibly, certain lifestyles or behaviors, 5 and appears to be the consequence of a genomewide phenomenon referred to as the CpG island methylator phenotype (CIMP). 6 Not surprisingly, epigenetic silencing of critical genes (such as those in the DNA MMR system) also occurs as a mechanism by which tumors develop in other organs.…”

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confidence: 99%

The silence of the genes: Matching mismatch repair defects with tumors

Boland

Goel

2003

Cancer

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This study examined the polymerizations of maleic anhydride in solution and in the bulk phase catalyzed by nanocrystalline titania or sodium acetate. Through IR and 1H‐NMR, the monomer and polymer were characterized, and the structure of the polymer was confirmed. Moreover, the polymer molecular weight was measured to be 400–800 in solution and 2000–3000 in the bulk phase. The mechanism of the catalytic polymerization was also investigated. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2868–2874, 2003

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Associations Between Cigarette Smoking, Lifestyle Factors, and Microsatellite Instability in Colon Tumors

Abstract: This study suggests that smoking cigarettes statistically significantly contributes to MSI in colon tumors. We estimate that approximately 21% of MSI in colon tumors may be attributable to cigarette smoking.

Cited by 303 publications

References 15 publications

DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer

DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer

Dietary intake and microsatellite instability in colon tumors

The silence of the genes: Matching mismatch repair defects with tumors

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